Acute Effects Of Donepezil On Brain Perfusion And Memory In Subjects With Cognitive Impairment And Mild Alzheimer's Disease

NCT01082965 | Terminated Results

• 1 other identifier: A9001437
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 8

Brief Summary

The study hypothesizes that donepezil will have a positive impact on brain blood flow deficits in subjects with memory deficits and/or mild dementia and that improvements in brain blood flow will be accompanied by improvements in memory.

Conditions

Alzheimer's Disease

Keywords

ASL MRI; perfusion; cognition; donepezil; alzheimer's disease; translational medicine

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1

  Posterior cingulate cortex perfusion was measured by arterial spin labeling (ASL). ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point.

  Baseline, 4 hours post-dose on Day 1

• Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 0 on Day 8

  Posterior cingulate cortex perfusion was measured by ASL. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point.

  Baseline, 1 minute post-dose (Hour 0) on Day 8

• Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 8

  Posterior cingulate cortex perfusion was measured by ASL. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point.

  Baseline, 4 hours post-dose on Day 8

Secondary Outcomes (4)

• Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8

  Baseline, 4 hours post-dose on Day 1, 1 minute post-dose (Hour 0), 4 hours post-dose on Day 8

• Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8

  Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8

• Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8

  Baseline, 5 hours post-dose on Day 8

• Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8

  Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8

Study Arms (2)

Treatment

EXPERIMENTAL

Drug: Donepezil

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Donepezil DRUG

5 mg tablets once daily for 7 days and then 10mg on 8th day

Treatment

Placebo DRUG

matching placebo

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects and caregivers must provide written Informed Consent and be willing to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
• AD: Diagnostic evidence of probable AD consistent with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria met by the site Physician at the time of the Screening visit. This evidence must be fully documented in the participant's file prior to the Baseline Visit.
• For amnestic Mild Cognitive Impairment (MCI): A Clinical Dementia Rating (CDR) of 0.5 (with memory box score of at least 0.5) and a memory complaint that is objectively verified using a test of episodic memory: Delayed recall from one paragraph of the Wechsler Logical Memory scale (cutoff scores by education - maximum score of 25).
• Less than or equal to 8 for 16 or more years of education; Less than or equal to 4 for 8-15 years of education; Less than or equal to 2 for 0-7 years of education.
• Mini Mental State Exam (MMSE) score of 21-30
• Male and female subjects of non child-bearing potential (or using appropriate birth control measures) who are at least 50 years of age.
• In generally good health, in the opinion of the Principal Investigator (PI), based on medical history, Body Mass Index (BMI), physical examination, vital signs, 12-lead ECG, and laboratory values, including hematology and chemistry values.
• No known genetic AD causes for early onset memory impairment (e.g., presenilin mutation), participants from a family with known autosomal dominant AD associated with mutations in APP, PS1, or PS2 genes or strongly suspected, but not yet identified mutations in APP, PS1 or PS2 genes or Down's syndrome are not eligible to enroll. Individuals from families with late onset AD with 2 or more affected family members may participate.
• Type II diabetic subjects may be included provided that their disease and serum glucose values are controlled and being actively managed, as assessed by the PI using a fasting blood sugar and/or HgbA1C (per the PI's medical judgment in consultation with the Sponsor).
• Rosen-Modified Hachinski Ischemia Score less than or equal to 4.

You may not qualify if:

• Diagnosis or history of other possible cause for or significant contributor to dementia, including but not limited to other neurodegenerative disorders (eg, frontotemporal dementia, Lewy body disease, vascular dementia), vitamin B12 deficiency (reflex Methylmalonic Acid (MMA) and folate if B12 is low), untreated thyroid disease, syphilis, alcoholism, severe or recurrent head injury that is clinically relevant to the disease under study, or onset of dementia following heart surgery or cardiac arrest.
• Diagnosis or history of cerebrovascular disease (eg, stroke, transient ischemic attack), severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage, or subdural hematoma that could contribute to the subject's current cognitive or functional status, impair ability to fully participate in the trial or that may impact status during the one week study.
• History of cancer within the last year (except for cutaneous basal cell, squamous cell cancer resolved by excision, colon polyp resolved by excision, or non-progressive prostate cancer per investigator's judgment).
• History of clinically significant cardiovascular or renal events.
• Subjects with uncontrolled hypertension even with therapeutic intervention
• History of clinically significant (as determined by the PI in consultation with the Sponsor) syncope, seizure, head trauma, or clinically significant unexplained loss of consciousness within the last 5 years.
• A diagnosis of major depressive disorder or other psychiatric illness as the primary diagnosis per the DSM-IV text revision (TR) criteria per the investigator's judgment.
• History of schizophrenia, bipolar disorder, or other severe mental illness.
• Known history of alcohol or drug abuse (as defined by the DSM-IV-TR) within 5 years prior to dosing or a positive result regarding use of illicit drugs on the drug screening test.
• History of clinically significant symptoms of pulmonary disease that requires treatment (eg. asthma, COPD, or other chronic respiratory conditions).
• Known positive Human immunodeficiency virus (HIV) status.
• Unwilling or unable to comply with the Life Style guidelines described in this protocol.
• Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) of Study Day 1.
• Use of tobacco- or nicotine-containing products within three months of study Day 1.
• Use of medication(s) for cognitive enhancement ≤ 90 days before the first dose of study medication.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (8)

Pfizer Investigational Site

San Francisco, California, 94122, United States

Location

Pfizer Investigational Site

San Francisco, California, 94143, United States

Location

Pfizer Investigational Site

Baltimore, Maryland, 21224, United States

Location

Pfizer Investigational Site

Baltimore, Maryland, 21287, United States

Location

Pfizer Investigational Site

St Louis, Missouri, 63108, United States

Location

Pfizer Investigational Site

St Louis, Missouri, 63110, United States

Location

Pfizer Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

Pfizer Investigational Site

Philadelphia, Pennsylvania, 19446, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

The study was terminated because of the prohibitively low recruitment rate and the reassessment of the Neuroscience Research Unit portfolio. The decision to terminate the study was not based on any safety or efficacy concerns.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2010
• First Posted: March 9, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: September 12, 2013
• Results First Posted: September 12, 2013

Record last verified: 2013-07

Locations

US (8)