Alzheimer's Disease

Alzheimer's Disease

221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease (ENGAGE)

Purpose of the Study: The primary objective of the study is to evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in participants with early AD. Secondary objectives are to assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale (13 items) [ADAS-Cog 13], and AD Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) [ADCS-ADL-MCI].


Eligibility Criteria:
Ages Eligible for Study: 50 Years to 85 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No


Key Inclusion Criteria:

  • Must meet all of the following clinical criteria for MCI due to AD or mild AD and must have:
  • A Clinical Dementia Rating (CDR)-Global Score of 0.5
  • Objective evidence of cognitive impairment at screening
  • An MMSE score between 24 and 30 (inclusive)
  • Must have a positive amyloid Positron Emission Tomography (PET) scan
  • Must consent to apolipoprotein E (ApoE) genotyping
  • If using drugs to treat symptoms related to AD, doses must be stable for at least 8 weeks prior to screening visit one
  • Must have a reliable informant or caregiver

Key Exclusion Criteria:

  • Any medical or neurological condition (other than Alzheimer's disease) that might be a contributing cause of the subject's cognitive impairment
  • Have had a stroke or transient ischemic attack (TIA) or unexplained loss of consciousness in the past one year
  • Clinically significant psychiatric illness in past six months
  • History of unstable angina, myocardial infarction, advanced chronic heart failure, or clinically significant conduction abnormalities within one year prior to Screening
  • Indication of impaired renal or liver function
  • Have human immunodeficiency virus (HIV) infection
  • Have a significant systematic illness or infection in past 30 days
  • Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
  • Any contraindications to brain magnetic resonance imaging (MRI) or PET scans
  • Alcohol or substance abuse in past one year
  • Taking blood thinners (except for aspirin at a prophylactic dose or less)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply


Study Status: This study is currently recruiting participants.


Principal Investigator: Biogen


Contact:
Jennifer Icenhour, CCRC
Clinical Research Manager
OSU Memory Disorders Research Center
OSU Department of Neurology
Phone: 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: Biogen

Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2)

Purpose of the Study: The purpose of this study is to build upon the information obtained in the original Alzheimer's Disease Neuroimaging Initiative (ADNI1) and ADNI-GO (Grand Opportunity; a study funded through an NIH grant under the American Recovery and Reinvestment Act), to examine how brain imaging technology can be used with other tests to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). ADNI2 seeks to inform the neuroscience of AD. This information will aid in the early detection of AD, and in measuring the effectiveness of treatments in future clinical trials.


Eligibility Criteria:
Ages Eligible for Study: 55 Years to 90 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Sampling Method: Probability Sample
Study Population
Community Sample
Criteria


Inclusion Criteria: Participants will be classified as either normal controls, SMC, EMCI, LMCI or AD participants. General Inclusion Criteria will apply to all groups, with specific criteria for each group as described below:

General (applies to each category):

  • Geriatric Depression Scale less than six
  • Age between *55-90 (inclusive). *For normal controls and SMC participants, age must be between 65-90
  • Study partner is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more), and can accompany the participant to all clinic visits for the duration of the protocol
  • Visual and auditory acuity adequate for neuropsychological testing
  • Good general health with no diseases expected to interfere with the study
  • Participant is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile)
  • Willing and able to participate in a longitudinal imaging study
  • Hachinski less than or equal to four
  • Completed six grades of education or has a good work history (sufficient to exclude mental retardation)
  • Must speak English or Spanish fluently
  • Willing to undergo repeated MRIs (3Tesla) and at least two PET scans (one FDG and one Amyloid imaging) and no medical contraindications to MRI
  • Agrees to collection of blood for Genome Wide Association Studies (GWAS), APOE testing and DNA and RNA banking
  • Agrees to collection of blood for biomarker testing
  • Agrees to at least one lumbar puncture for the collection of CSF

Specific Inclusion Criteria for normal controls:

  • Participant must be free of memory complaints, verified by a study partner
  • Normal memory function score on Wechsler Memory Scale (adjusted for education)
  • Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)
  • Clinical Dementia Rating (CDR) = 0; Memory Box score must be 0
  • Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living
  • Stability of Permitted Medications for four weeks. In particular, participants may take:
  1. Antidepressants lacking significant anticholinergic side effects
  2. Estrogen replacement therapy is permissible
  3. Gingko biloba is permissible, but discouraged
  4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least four weeks prior to screening

Specific Inclusion Criteria for SMC participants:

  • Subjects that are "self-referrals" that have a significant subjective memory concern
  • Significant memory concern confirmed by a Cognitive Change Index score of more than or equal to 16
  • Normal memory function score on Wechsler Memory Scale (adjusted for education)
  • Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)
  • Clinical Dementia Rating (CDR) = 0; Memory Box score must be 0
  • Cognitively normal, based on the absence of significant memory impairment in cognitive function or activities of daily living
  • Stability of permitted medications for four weeks. In particular, subjects may take:
  1. Antidepressants lacking significant anticholinergic side effects
  2. Estrogen replacement therapy is permissible
  3. Gingko biloba is permissible, but discouraged
  4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening

Specific Inclusion Criteria for EMCI and LMCI participants:

  • Participant must have a subjective memory concern as reported by participant, study partner, or clinician
  • Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
  • Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)
  • Clinical Dementia Rating (CDR) = 0.5; Memory Box score must be at least 0.5
  • General cognition and functional performance sufficiently preserved such that a diagnosis of AD cannot be made by the site physician at the time of the screening visit
  • Stability of Permitted Medications for four weeks. In particular, participants may take:
  1. Antidepressants lacking significant anticholinergic side effects
  2. Estrogen replacement therapy
  3. Gingko biloba is permissible, but discouraged
  4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least four weeks prior to screening
  5. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screening

Specific Inclusion Criteria for AD participants:

  • Participant must have a subjective memory concern as reported by participant, study partner, or clinician
  • Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
  • Mini-Mental State Exam (MMSE) score between 20 and 26 (inclusive)
  • Clinical Dementia Rating (CDR) = 0.5 or 1.0
  • National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD
  • Stability of Permitted Medications for four weeks. In particular, participants may take:
  1. Antidepressants lacking significant anticholinergic side effects
  2. Estrogen replacement therapy
  3. Gingko biloba is permissible, but discouraged
  4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least four weeks prior to screening
  5. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screening

Specific Inclusion Criteria for follow-up participants from ADNI1 and ADNI GO:

  • Must have been enrolled and followed in ADNI1 for at least one year or enrolled in ADNI-GO with original diagnosis of Cognitively Normal (CN), Mild Cognitive Impairment (MCI), or Early Mild Cognitive Impairment (EMCI) regardless of whether a diagnostic conversion has occurred since initial enrollment in ADNI
  • Willing and able to continue to participate in an ongoing longitudinal study. A reduced battery of tests is allowable if the participant is not able/willing to complete the full battery
  • Study partner is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more), and can accompany the participant to all clinic visits for the duration of the protocol

Exclusion Criteria:

General (applies to each category):

  • Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions; Participants with multiple lacunes or lacunes in a critical memory structure are excluded
  • Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body
  • Major depression, bipolar disorder as described in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) within the past one year
  • Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder
  • History of schizophrenia
  • History of alcohol or substance abuse or dependence within the past two years
  • Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
  • Clinically significant abnormalities in B12, or TFTs that might interfere with the study
  • Residence in skilled nursing facility
  • Current use of specific psychoactive medications (e.g.,certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.); Current use of warfarin or dabigatran (exclusionary for lumbar puncture)
  • Use of investigational agents one month prior to entry and for the duration of the trial
  • Participation in clinical studies involving neuropsychological measures being collected more than one time per year
  • Exclusion for FDG PET scan and amyloid imaging with Florbetapir F 18: Current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the participant in any given year would exceed the limits of annual and total dose commitment set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.1.
  • Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director

Specific Exclusion Criteria for normal controls and SMC participants: Any significant neurologic disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities


Specific Exclusion Criteria for EMCI and LMCI participants: Any significant neurologic disease other than suspected incipient Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.


Specific Exclusion Criteria for AD participants: Any significant neurologic disease other than Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.


Specific Exclusion Criteria for follow-up participants from ADNI1 and ADNI GO: Participants will not be able to participate in FDG PET scan and amyloid imaging with Florbetapir F 18 if the following is true: Current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the participant in any given year would exceed the limits of annual and total dose commitment set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.1.


Study Status: This study is ongoing, but not recruiting participants


Principal Investigator: Alzheimer's Disease Cooperative Study (ADCS)


Contact:
Jennifer Icenhour, CCRC
Clinical Research Manager
OSU Memory Disorders Research Center
OSU Department of Neurology
Phone: 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: Alzheimer's Disease Cooperative Study (ADCS)

An Efficacy and Safety Study of AZD3293 in Early Alzheimer's Disease (AMARANTH)

Purpose of the Study: The purpose of this study is to assess the efficacy and safety of AZD3293 compared with placebo administered for 104 weeks in the treatment of early Alzheimer´s disease. The study will test the hypothesis that AZD3293 is a disease-modifying treatment for patients with early Alzheimer´s disease, defined as the continuum of patients with MCI due to Alzheimer´s disease and patients diagnosed with mild dementia of the Alzheimer´s type, as measured by change from baseline in the Clinical Dementia Rating-Sum of Boxes score at week 104 in each of the 2 AZD3293 treatment groups compared with placebo.


Eligibility Criteria:
Ages Eligible for Study: 55 Years to 85 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No


Inclusion Criteria:

  • Gradual and progressive change in the patient's memory function over more than six months, reported by patient and study partner
  • MMSE score of 20-30 inclusive at screening visit
  • Objective impairment in memory as evaluated by memory test performed at screening visit
  • For a diagnosis of mild Alzheimer's disease (AD), patient meets the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria for probable AD
  • For a diagnosis of MCI due to AD, patient meets NIA-AA criteria for MCI due to AD

Exclusion Criteria:

  • Significant neurological disease affecting the CNS, other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson´s disease, or epilepsy or recurrent seizures
  • History of clinically evident stroke, or multiple strokes based on history or imaging results
  • History of clinically important carotid or vertebrobasilar stenosis or plaque
  • History of multiple concussions with sustained cognitive complaints or objective change in neuropsychological function in the last five years
  • Patients with a current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of Major Depressive Disorder or any current primary psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the patient´s ability to complete the study
  • History of alcohol or drug abuse or dependence (except nicotine dependence) within two years before the screening visit
  • Within one year before the screening visit or between screening and baseline, any of the following: myocardial infarction; moderate or severe congestive heart failure, NYHA class III or IV; hospitalization for, or symptom of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (e.g., significant valvular disease, hypertrophic cardiomyopathy), or hospitalization for arrhythmia
  • Congenital QT prolongation
  • History of cancer within the last five years, with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical, or non-progressive prostate cancer
  • Current serious or unstable clinically important systemic illness that, in the judgment of the investigator, is likely to affect cognitive assessment, deteriorate or affect the patient's safety or ability to complete the study, including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic or hematologic disorders

Study Status: This study is currently recruiting participants.


Principal Investigator: AstraZeneca, Eli Lilly and Company


Contact:
Jennifer Icenhour, CCRC
Clinical Research Manager
OSU Memory Disorders Research Center
OSU Department of Neurology
Phone: 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: AstraZeneca, Eli Lilly and Company

Deep Brain Stimulation for the Treatment of Alzheimer's Disease

Purpose of the Study: The purpose of this clinical study is to investigate the safety and efficacy of deep brain stimulation (DBS) as a treatment option for patients with cognitive, behavioral and functional disability of Alzheimer's disease.


Eligibility Criteria:
Ages Eligible for Study: 45 Years to 85 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No


Inclusion Criteria:

  • Diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria

Exclusion Criteria:

  • Has significant neurological disease, other than Alzheimer's disease, e.g., multiple sclerosis, Parkinson's disease and ischemic stroke, or severe brain atrophy or the presence of subdural hygromas or subdural hematomas
  • Evidence of substance abuse (alcohol or other drug) abuse or dependence during the previous 12 months (DSM-IV Criteria)

Study Status: This study is currently recruiting participants.


Principal Investigator: Ali Rezai, MD


Contact:
Jennifer Icenhour
Phone: 614-293-6882 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: The Ohio State University

Study of the Safety and Effectiveness of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease

Purpose of the Study: The purpose of this study is to evaluate the safety and efficacy of two fixed doses of EVP-6124 compared to placebo for 26 weeks in subjects with mild to moderate Alzheimer's disease currently receiving stable treatment or previously treated with an acetylcholinesterase inhibitor.


Eligibility Criteria:
Ages Eligible for Study: 55 Years to 85 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No


Inclusion Criteria:

  • Ages ≥55 and ≤85 years
  • Informed consent form (ICF) signed by the subject or legally acceptable representative before any study-specific procedures for the subject are performed and an ICF signed by the support person/caregiver before any study-specific procedures for the support person/caregiver are performed
  • Clinical diagnosis of dementia due to probable AD consistent with criteria established by a workgroup of the National Institute on Aging and the Alzheimer's Disease Association
  • Clinical decline within 12 months before screening and onset of symptoms at least 12 months or longer before screening, which may include any documented cognition, functional, or other objective assessment or the clinical judgment of the investigator or the subject's referring physician that the subject has experienced a clinical decline within the last 12 months
  • Magnetic resonance imaging (MRI) or computed tomography (CT) scan performed within 12 months before screening, with findings consistent with the diagnosis of dementia due to AD without any other clinically significant comorbid pathologies. If an MRI or CT scan is unavailable or occurred greater than 12 months before screening, this assessment should be completed and the findings confirmed before the subject enters the run-in period (day -14) (copy of the report will be available at the study site)
  • Mini-Mental State Examination (MMSE) score ≥14 and ≤24 at screening and confirmed on day one prior to randomization (fluctuations of ±2 points are acceptable on day one/baseline)
  • Clinical Dementia Rating Global score (CDR-GS) ≥1 (at least mild dementia) at screening and confirmed on day one prior to randomization
  • Modified Hachinski Ischemic Scale (mHIS) score ≤4 at screening
  • Fertile, sexually active subjects (men and women) must use an effective method of contraception during the study. Female subjects and the female partner of male subjects must be surgically sterile (hysterectomy or bilateral tubal ligation), postmenopausal for at least one year, or willing to practice adequate methods of contraception if of childbearing potential (defined as consistent use of combined effective methods of contraception [including at least one barrier method])
  • Reliable and capable support person/caregiver, who if not living in the same household, interacts with the subject approximately four times per week and will be available to attend clinic visits in person when possible
  • Subject living at home, senior residential setting, or an institutional setting without the need for continuous (i.e., 24-hour) nursing care
  • General health status acceptable for participation in a 26-week study
  • Fluency (oral and written) in the language in which the standardized tests will be administered
  • Receiving a stable dose of an acetylcholinesterase inhibitor (AChEI) (donepezil, rivastigmine or galantamine) for at least three months (90 days) before screening and with continuous dosing for at least six months OR not presently receiving an AChEI (at least 30 days before screening), but with a history of previous AChEI treatment (subjects receiving donepezil 23 mg currently or within three months before screening are ineligible)

Exclusion Criteria:

  • Exposure to an experimental drug, experimental biologic or experimental medical device within two months (60 days) before screening
  • Prior participation in an amyloid vaccination clinical study at any time in the past or completion of a passive amyloid vaccination study within six months before screening
  • Inability to swallow a tablet
  • In the judgment of the investigator, inability of the subject or the support person/caregiver to complete a 26-week study
  • Inability to be ≥75% compliant with single-blind study drug
  • Inability to adequately cooperate or complete the cognitive testing procedures or any study assessment
  • Residence in a skilled nursing facility
  • Untreated vitamin B12 or folate deficiency (if treated, must be stably treated for at least 6 months before screening)
  • Clinically significant (in the judgment of the investigator) abnormal serum electrolytes (sodium, potassium, magnesium) after repeat testing
  • Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating hormone level and thyroid supplementation dose must be stable for at least six months before screening)
  • Insufficiently controlled diabetes mellitus (in the judgment of the investigator) or requiring insulin
  • Renal insufficiency (serum creatinine >2.0 mg/dL)
  • Malignant tumor within three years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or localized prostate cancer)
  • Female subjects who are pregnant, nursing or planning to become pregnant during the study
  • Unstable medical condition that is clinically significant in the judgment of the investigator
  • Alanine transaminase (ALT) or aspartate transaminase (AST) >2.5 times the upper limit of normal
  • History of myocardial infarction or unstable angina within six months before screening
  • History of more than one myocardial infarction within five years before screening
  • Clinically significant (in the judgment of the investigator) cardiac arrhythmia (including atrial fibrillation), cardiomyopathy or cardiac conduction defect (subjects with a pacemaker are acceptable)
  • Symptomatic hypotension or hypertension (supine diastolic blood pressure >95 mmHg) (in the judgment of the investigator)
  • Clinically significant abnormality on screening or baseline electrocardiogram (ECG), including but not necessarily limited to a confirmed corrected QT interval (QTc) value ≥450 msec for males or ≥470 msec for females. In subjects with a QRS value >120msec, those with a QTc value <500 msec may be eligible following discussion with the Medical Monitor.
  • Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia
  • History of brain tumor, subdural hematoma, or other clinically significant (in the judgment of the investigator) space-occupying lesion on CT or MRI
  • Head trauma with clinically significant (in the judgment of the investigator) loss of consciousness within 12 months before screening or concurrent with the onset of dementia
  • Onset of dementia secondary (in the judgment of the investigator) to cardiac arrest, surgery with general anesthesia or resuscitation
  • Specific degenerative central nervous system (CNS) disease diagnosis other than AD (e.g., Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, frontotemporal dementia, Parkinson's disease)
  • Subjects with no history of prior treatment with an AChEI (donepezil, rivastigmine, or galantamine)
  • Memantine currently or within 30 days before screening
  • Antipsychotics; low doses (in the judgment of the investigator, except clozapine) are allowed only if given for sleep disturbances, agitation and/or aggression, and only if the subject has received a stable dose for at least three months before screening (but not within 8 hours before any cognitive test)
  • Tricyclic antidepressants and monoamine oxidase inhibitors; all other antidepressants are allowed only if the subject has received a stable dose for at least 3 months before screening
  • Antiepileptic medications if taken for control of seizures
  • Chronic intake of opioid-containing analgesics
  • Sedating H1 antihistamines
  • Nicotine therapy (including the patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening
  • Clinically significant urine drug screen or serum alcohol test result in the judgment of the investigator
  • History of ischemic colitis or ischemic enterocolitis

Study Status: This study is currently recruiting participants.


Principal Investigator: FORUM Pharmaceuticals Inc.


Contact:
Jennifer Icenhour, CCRC
Clinical Research Manager
OSU Memory Disorders Research Center
OSU Department of Neurology
Phone: 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: FORUM Pharmaceuticals Inc.

Study of Lu AE58054 in Patients With Mild - Moderate Alzheimer's Disease Treated With Donepezil (STARSHINE)

Purpose of the Study: To establish efficacy of Lu AE58054 as adjunctive therapy to donepezil for symptomatic treatment of patients with mild-to-moderate Alzheimer's disease (AD).


Eligibility Criteria:
Ages Eligible for Study: 50 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No


Inclusion Criteria:

  • The patient has a knowledgeable and reliable caregiver
  • The patient is an outpatient
  • The patient has probable AD
  • The patient has mild to moderate AD
  • Stable treatment with donepezil
  • The patient, if a woman, must have had her last natural menstruation ≥24 months prior to baseline, OR be surgically sterile
  • The patient, if a man, agrees to protocol-defined use of effective contraception if his female partner is of childbearing potential, OR must have been surgically sterilized prior to the screening visit

Exclusion Criteria:

  • The patient has evidence of any clinically significant neurodegenerative disease, or other serious neurological disorders other than AD
  • The patient has a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) Axis I disorder other than AD
  • The patient has evidence of clinically significant disease
  • The patient's donepezil therapy is likely to be interrupted or discontinued during the study
  • The patient is currently receiving memantine or has taken memantine within 2 months prior to screening

Other inclusion and exclusion criteria may apply.


Study Status: This study is currently recruiting participants.


Principal Investigator: H. Lundbeck A/S


Contact:
Jennifer Icenhour, CCRC
Clinical Research Manager
OSU Memory Disorders Research Center
OSU Department of Neurology
Phone: 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: H. Lundbeck A/S

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Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012)

Purpose of the Study: The purpose of this multicenter trial is to assess the efficacy and safety of MK-7622 compared with placebo as adjunctive therapy to acetylcholinesterase inhibitors (AChEIs) for the symptomatic treatment of participants with mild to moderate Alzheimer's Disease (AD). The trial consists of two stages: Stage 1 and Stage 2. Participants in Stage 1 will be randomized to receive either placebo or MK-7622 45 mg once daily. In Stage 2, participants will be randomized to receive either placebo, or MK-7622 5, 15 or 45 mg once daily. Participants will be enrolled in only one stage. Interim analyses will be performed in both Stage 1 and Stage 2 to determine whether the trial should continue. Duration of each stage is approximately 26 weeks; all participants receive placebo at some time during the trial. The primary study hypotheses are the following: Stage 1 - MK-7622 45 mg once daily is superior to placebo in improving cognition in participants with mild to moderate AD as assessed by mean change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) at Week 12; Stage 2 - At least one of the top two doses of MK-7622 (15 mg once daily, 45 mg once daily) is superior to placebo in improving cognition in participants with mild to moderate AD as assessed by mean change from baseline in ADAS-Cog11 at Week 12.


Eligibility Criteria:
Ages Eligible for Study: 55 Years to 85 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No


Inclusion Criteria:

  • Diagnosis of probable AD based on both a) the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and b) the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for AD
  • AD is of mild to moderate severity
  • Clear history of cognitive and functional decline over at least one year that is either a) documented in medical records or b) documented by history from an informant who knows the participant well
  • On a stable and effective daily dose of AChEI (either donepezil, rivastigmine, or galantamine), for at least two months before Screening, and willing to remain on the same dose for the duration of the trial. Effective doses are considered to be: donepezil, 10 mg total daily dose administered orally; rivastigmine, 9.5 or 13.3 mg/24 hours administered by transdermal patch or 6-12 mg total daily dose administered orally; galantamine, 16-24 mg total daily dose administered orally
  • Able to read at a 6th grade level or equivalent, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation
  • Participant must have a reliable and competent trial partner who must have a close relationship with the subject

Exclusion Criteria:

  • History of clinically significant stroke
  • Evidence of a neurological disorder other than the disease being studied (i.e., probable AD)
  • History of seizures or epilepsy within the last five years before screening
  • Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
  • Participant is at imminent risk of self-harm or of harm to others
  • History of alcoholism or drug dependency/abuse within the last five years before screening
  • Participant does not have a magnetic resonance imaging (MRI) scan obtained within 12 months of screening and is unwilling or not eligible to undergo an MRI scan at screening
  • History of hepatitis or liver disease that has been active within the six months prior to screening visit
  • Recent or ongoing, uncontrolled, clinically significant medical condition within 3 months of the screening Visit (e.g., diabetes, hypertension, thyroid or endocrine disease, congestive heart failure, angina, cardiac or gastrointestinal disease, dialysis or abnormal renal function) other than the condition being studied such that participation in the trial would pose a significant medical risk to the participant. Controlled co-morbid conditions are not exclusionary if stable within three months of the screening visit
  • History or current evidence of long QT syndrome, corrected QT (QTc) interval ≥470 milliseconds (for male subjects) or ≥480 milliseconds (for female subjects), or torsades de pointes
  • History of malignancy occurring within the five years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma which has been treated with potentially curative therapy with no evidence of recurrence for ≥3 year post therapy
  • Clinically significant vitamin B12 deficiency, or increased thyroid stimulating hormone (TSH) in the six months before screening
  • Major surgery within three months of screening

Study Status: This study is currently recruiting participants.


Principal Investigator: Merck Sharp & Dohme Corp.


Contact:
Jennifer Icenhour, CCRC
Clinical Research Manage
OSU Memory Disorders Research Center
OSU Department of Neurology
Phone: 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: Merck Sharp & Dohme Corp.

Efficacy and Safety Trial of MK-8931 in Participants With Prodromal Alzheimer's Disease (MK-8931-019) (APECS)

Purpose of the Study: The purpose of this trial is to assess the efficacy and safety of MK-8931 compared with placebo in the treatment of amnestic mild cognitive impairment (aMCI) due to Alzheimer's disease (AD), also known as prodromal AD. Participants will be randomized to receive placebo, or 12 mg or 40 mg MK-8931, once daily. The primary study hypothesis is that at least one MK-8931 dose is superior to placebo with respect to the change from baseline in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) score at 104 weeks.


Eligibility Criteria:
Ages Eligible for Study: 50 Years to 85 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No


Inclusion Criteria:

  1. Diagnosis of prodromal AD, including the following:
  1. History of subjective memory decline with gradual onset and slow progression for at least one year corroborated by an informant
  2. Objective impairment in episodic memory by memory test performed at screening
  3. Does not meet criteria for dementia, AND
  4. Positive Screening amyloid imaging PET scan using [18F]flutametamol tracer or positive Screening CSF tau:amyloid-β42 (Aβ42) ratio
  1. Able to read at a 6th grade level or equivalent
  2. If participant is receiving an acetylcholinesterase inhibitor or memantine, the dose must have been stable for at least three months before screening
  3. Must have a reliable and competent trial partner/informant who has a close relationship with the participant, is willing to accompany the participant to all required trial visits, and is willing to monitor compliance of the administration of the trial medication

Exclusion Criteria:

  1. History of stroke
  2. Evidence of a clinically relevant neurological disorder other than the disease being studied (i.e., prodromal AD)
  3. History of seizures or epilepsy within the last five years
  4. Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
  5. Participant is at imminent risk of self-harm or of harm to others
  6. History of alcoholism or drug dependency/abuse within the last five years before screening
  7. Participant does not have a magnetic resonance imaging (MRI) scan obtained within 12 months of screening and is unwilling or not eligible to undergo an MRI scan at the screening visit. With sponsor approval, a head computed tomography (CT) scan may be substituted for MRI scan to evaluate eligibility
  8. History of hepatitis or liver disease that has been active within the six months prior to screening
  9. Recent or ongoing, uncontrolled, clinically significant medical condition within three months of screening
  10. History of malignancy occurring within the five years before screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma
  11. Clinically significant vitamin B12 or folate deficiency in the six months before Screening
  12. Use of any investigational drugs or participation in clinical trials within the 30 days before screening
  13. History of a hypersensitivity reaction to more than three drugs
  14. Has human immunodeficiency virus (HIV) by medical history
  15. Participant is unwilling or has a contraindication to undergo PET scanning including but not limited to claustrophobia, excessive weight or girth
  16. History or current evidence of long QT syndrome, corrected QT (QTc) interval ≥470 milliseconds (for male participants) or ≥480 milliseconds (for female participants), or torsades de pointes
  17. Close family member (including the trial partner, spouse or children) who is among the personnel of the investigational or sponsor staff directly involved with this trial

Study Status: This study is currently recruiting participants


Principal Investigator: Merck Sharp & Dohme Corp.


Contact:
Jennifer Icenhour, CCRC
Clinical Research Manager
OSU Memory Disorders Research Center
OSU Department of Neurology Phone: 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: Merck Sharp & Dohme Corp.

An Efficacy and Safety Trial of MK-8931 in Mild to Moderate Alzheimer's Disease (P07738) (EPOCH)

Purpose of the Study: This study consists of two parts, Part I and Part II. The purpose of Part I of the study is to assess the efficacy and safety of MK-8931 compared with placebo administered for 78 weeks in the treatment of Alzheimer's Disease (AD). The primary study hypotheses for Part I are that at least one MK-8931 dose is superior to placebo at 78 weeks of treatment with respect to change from Baseline in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) score and that at least one MK-8931 dose is superior to placebo at 78 weeks of treatment with respect to change from Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) score. The first approximately 400 participants entering Part I of the study are identified as the Safety Cohort. Participants who complete Part I of the study may choose to participate in Part II, which is a long term double-blind extension to assess efficacy and safety of MK-8931 administered for up to an additional 260 weeks.


Eligibility Criteria:
Ages Eligible for Study: 55 Years to 85 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No


Inclusion Criteria:

  • Diagnosis of probable AD based on both a) the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and b) the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for AD
  • AD is of mild to moderate severity
  • Clear history of cognitive and functional decline over at least one year that is either a) documented in medical records or b) documented by history from an informant who knows the subject well
  • Able to read at a sixth grade level or equivalent, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation
  • If a participant is receiving an acetylcholinesterase inhibitor, memantine, medical food/supplement (e.g., vitamin E) and/or herbal medications for AD, the dose must have been stable for at least three months before Screening, and the participant must be willing to remain on the same dose for the duration of the trial. Participants may need to be on AD treatments in accordance with local requirements
  • Participant must have a reliable and competent trial partner/caregiver who must have a close relationship with the subject

Inclusion Criteria for Extension Period (Part II):

  • Tolerated study drug and completed the initial 78-week period of the trial (Part I)
  • Participant must have a reliable and competent trial partner who must have a close relationship with the subject

Exclusion Criteria:

  • History of stroke
  • Evidence of a neurological disorder other than the disease being studied (i.e., probable AD)
  • History of seizures or epilepsy within the last five years before screening
  • Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
  • Participant is at imminent risk of self-harm or of harm to others
  • History of alcoholism or drug dependency/abuse within the last 5 years before screening
  • Participant does not have a magnetic resonance imaging (MRI) scan obtained within 12 months of Screening and is unwilling or not eligible to undergo an MRI scan at the screening visit. With Sponsor approval, a head computed tomography (CT) scan may be substituted for MRI scan to evaluate eligibility
  • History of hepatitis or liver disease that has been active within the six months prior to screening visit
  • Recent or ongoing, uncontrolled, clinically significant medical condition within 3 months of the Screening Visit (e.g., diabetes, hypertension, thyroid or endocrine disease, congestive heart failure, angina, cardiac or gastrointestinal disease, dialysis, or abnormal renal function) other than the condition being studied such that participation in the trial would pose a significant medical risk to the subject. Controlled co-morbid conditions are not exclusionary if stable within three months of the screening visit
  • History or current evidence of long QT syndrome, corrected QT (QTc) interval ≥470 milliseconds (for male subjects) or ≥480 milliseconds (for female subjects), or torsades de pointes
  • History of malignancy occurring within the five years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma; or malignancy which has been treated with potentially curative therapy with no evidence of recurrence for ≥3 year post-therapy
  • Clinically significant vitamin B12 or folate deficiency in the six months before screening Visit
  • Use of any investigational drugs within 30 days (or longer depending on drug) before screening or participation in studies involving repeated cognitive testing within 30 days before screening. Participation in an observational study, such as those involving annual cognitive assessments and/or neuroimaging, may be allowed if approved by sponsor
  • History of a hypersensitivity reaction to more than three drugs
  • Has tested positive for human immunodeficiency virus (HIV)
  • Close family member (including the caregiver, the spouse or any children) who is among the personnel of the investigational or sponsor staff directly involved with this trial

Additional Exclusion Criteria for Safety Cohort:

  • History of an ongoing medical condition that has been poorly controlled within 6 months of the screening visit (e.g., hypotension, diabetes, hypertension, cerebrovascular disease, thyroid disease, endocrine disturbance, congestive heart failure, cardiac or gastrointestinal disease, dialysis, or abnormal renal function) other than the condition being studied such that a subject's participation in the trial would pose a significant medical risk
  • History of congestive heart failure (moderate or greater severity), myocardial infarction, heart surgery, syncope, bradycardia or clinically significant hypotension within one year before screening

Exclusion Criteria for Extension Period (Part II):

  • Participant is at imminent risk of self-harm or of harm to others
  • Has developed a recent or ongoing, uncontrolled, clinically significant medical condition other than AD
  • Has history of or has developed during Part I evidence of long QT syndrome, QTc interval ≥470 milliseconds (for male subjects) or ≥480 milliseconds (for female subjects), or torsades de pointes
  • Has developed a form of dementia that is not AD

Study Status: This study is currently recruiting participants.


Principal Investigator: Merck Sharp & Dohme Corp


Contact:
Jennifer Icenhour, CCRC
Clinical Research Manager
OSU Memory Disorders Research Center
OSU Department of Neurology
Phone: 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: Merck Sharp & Dohme Corp

Progress of Mild Alzheimer's Disease in Participants on Solanezumab Versus Placebo (EXPEDITION 3)

Purpose of the Study: To test the idea that solanezumab will slow the cognitive and functional decline of Alzheimer's Disease (AD) as compared with placebo in participants with mild AD.


Eligibility Criteria:
Ages Eligible for Study: 55 Years to 90 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No


Inclusion Criteria:

  • Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD
  • Has a Modified Hachinski Ischemia Scale score of less than or equal to four
  • Has a Mini-Mental State Examination (MMSE) score of 20 through 26 at Screening visit
  • Has a Geriatric Depression Scale score of less than or equal to six (on the staff-administered short form)
  • Has had a magnetic resonance imaging (MRI) or computerized tomography (CT) scan performed within the past two years that has confirmed no findings inconsistent with a diagnosis of AD
  • Has a florbetapir positron emission tomography (PET) scan or cerebrospinal fluid (CSF) result consistent with the presence of amyloid pathology at screening

Exclusion Criteria:

  • Does not have a reliable caregiver who is in frequent contact with the participant (defined as at least 10 hours per week), will accompany the participant to the office and/or be available by telephone at designated times, and will monitor administration of prescribed medications
  • Meets National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia
  • Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study; or has a life expectancy of <two years
  • Has had a history within the last five years of a serious infectious disease affecting the brain or head trauma resulting in protracted loss of consciousness
  • Has a history within the last five years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen posttreatment
  • Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions
  • Has received acetylcholinesterase inhibitor (AChEIs), memantine and/or other AD therapy for less than four months or has less than two months of stable therapy on these treatments
  • Has received medications that affect the central nervous system (CNS), except treatments for AD, for less than four weeks
  • Has a history of chronic alcohol or drug abuse/dependence within the past five years

Study Status: This study is ongoing, but not recruiting participants


Principal Investigator: Eli Lilly and Company


Contact:
Jennifer Icenhour, CCRC
Clinical Research Manager
OSU Memory Disorders Research Center
OSU Department of Neurology
Phone: 614-293-6882, Fax: 614-366-6230
E-mail: Jennifer.Icenhour@osumc.edu


Funding: Eli Lilly and Company

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