Resveratrol for Alzheimer's Disease

May 6, 2016 updated by: Alzheimer's Disease Cooperative Study (ADCS)

Phase II Study to Evaluate the Impact on Biomarkers of Resveratrol Treatment in Patients With Mild to Moderate Alzheimer's Disease

Resveratrol is derived from plants and is found in highest levels in red wine and the skin of red grapes. A recent study reported that monthly and weekly consumption of red wine is associated with a lower risk of dementia. There is compelling evidence that caloric restriction can improve overall health by activating a class of enzymes known as Sirtuins. Resveratrol is a substance found in some plants that directly activates sirtuins, mimicking the effects of caloric restriction and may affect regulatory pathways of diseases of aging, including Alzheimer's disease (AD).

In this study, people with AD will be given either Resveratrol or placebo for 12 months to determine whether daily resveratrol therapy is beneficial in delaying or altering the deterioration of memory and daily functioning. Subjects age 50 and above with a diagnosis of probable AD may qualify for participation in this study. A small group of 15 participants will be asked to take part in a more detailed 24-hour Pharmacokinetic (PK) sub-study that will measure resveratrol levels over a 24 hour period.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This double blind, placebo-controlled trial will be conducted at approximately 26 Alzheimer's Disease Cooperative Study (ADCS) clinical centers. One hundred twenty (120) patients with mild to moderate dementia due to probable Alzheimer's disease (AD) will be randomly assigned to treatment (1:1) with resveratrol starting at 500 mg once daily or matching placebo, increasing at 13 week intervals to a maximum of 1 gram twice daily (divided into two 500 mg capsules taken orally) taken with or without food. Participants will be treated for 52 weeks, and will undergo venous blood draws for biomarker analysis at Baseline and at 52 weeks; participants will also undergo two lumbar punctures for biomarker analyses of cerebrospinal fluid (CSF) at Baseline and at Week 52. Participants will undergo magnetic resonance imaging (MRI) to measure rate of whole-brain and regional atrophy at Screening, Week 13 and Week 52 visits. Randomization will be stratified by site. For monitoring of potential toxicities of the study drug - particularly nephrotoxicity - subjects will undergo physical examination, neurological examination, adverse event review, blood chemistries to include blood urea nitrogen (BUN) and Creatinine (Cr), pharmacokinetic (PK) analyses for resveratrol and its metabolites, and urinalysis every 6-7 weeks during the study. Clinical, Cognitive and Functional effects of resveratrol and insulin and glucose metabolism will also be assessed.

A subgroup of approximately 15 subjects enrolled will be randomized 4:1 (N = 15, 12 treated + 3 placebo) for more detailed 24-hour PK analysis. For these individuals, blood samples will be collected at 15 different time points. Measurements will include levels of resveratrol and its major metabolites (sulfated- and glucuronidated-resveratrol). These subjects will complete the detailed PK with each dosage step. This 24-hour PK sampling in the subgroup will occur after the first dose following Baseline, after the first dose at each dose increment (Weeks 13, 26 and 39), and after the final dose (Week 52).

Enrollment will be restricted to individuals who are able to abstain from ingesting large quantities of resveratrol-containing foods (including red wine). 1-2 glasses of red wine or red grape juice and 1 serving of red grapes daily is acceptable. Subjects must also be able to abstain from ingesting herbal/natural preparations or dietary supplements containing resveratrol.

Study Type

Interventional

Enrollment (Actual)

119

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner Alzheimer's Institute
    • California
      • Irvine, California, United States, 92697
        • University of California, Irvine
      • La Jolla, California, United States, 92037
        • University of California, San Diego - Comprehensive Alzheimer's Program
      • Los Angeles, California, United States, 90033
        • University of Southern California
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
        • Georgetown University
      • Washington, District of Columbia, United States, 20060
        • Howard University
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic, Jacksonville
      • Tampa, Florida, United States, 33613
        • University of South Florida
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Kansas
      • Kansas City, Kansas, United States, 66205
        • University of Kansas
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • University of Kentucky
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins University
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic, Rochester
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Cleveland Clinic Lou Ruvo Center for Brain Health
    • New York
      • New York, New York, United States, 10032
        • Columbia University
      • New York, New York, United States, 10016
        • New York University
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine
      • Rochester, New York, United States, 14620
        • University of Rochester Medical Center
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • Case Western Reserve University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • South Carolina
      • N. Charleston, South Carolina, United States, 29406
        • Medical University of South Carolina
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Washington
      • Seattle, Washington, United States, 98108
        • U of WA / VA Puget Sound Alzheimer's Disease Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of probable AD (NINDS-ADRDA criteria).
  • Age must be 50 years or older.
  • Able to ingest oral medications.
  • Caregiver/Study Partner who has direct contact with the participant more than 2 days per week to accompany participant to all visits.
  • MMSE score between 14 and 26 (inclusive).
  • Modified Hachinski score of less than or equal to 4.
  • Able to abstain from ingesting large quantities of resveratrol-containing foods (including red wine). 1-2 glasses of red wine or red grape juice daily acceptable; 1 serving of red grapes daily acceptable.
  • Able to abstain from ingesting herbal/natural preparations or dietary supplements containing resveratrol.

Exclusion Criteria:

  • Non-AD dementia.
  • Probable AD with Down syndrome.
  • History of clinically significant stroke.
  • Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse.
  • Sensory impairment that would preclude the participant from participating in or cooperating with the protocol.
  • Use of investigational agent within two months of Screening.
  • Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal or other systemic disease or laboratory abnormality.
  • Active neoplastic disease, history of cancer five years prior to screening, including breast cancer (history or skin melanoma or stable prostate cancer are not excluded).
  • History of seizure within past five years.
  • Pregnancy or possible pregnancy.
  • Use of resveratrol containing supplements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Resveratrol
Subjects will take 500 mg by mouth once daily increasing at 13 week intervals to a maximum of 1 gram by mouth twice daily with or without food.
Drug: Resveratrol
The dosage will begin at 500 mg taken once daily and increase at 13 week intervals to 1 gram taken by mouth twice daily, supplied as 500 mg capsules (two capsules twice daily).
Placebo Comparator: Placebo
Subjects will receive a matching placebo to be taken with or without food.
Drug: Placebo
The matching placebo will begin at a capsule taken once daily and increase at 13 week intervals to two capsules twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Adverse Events
Time Frame: Baseline, Weeks 6, 13, 19, 26, 32, 39, 45, and 52
The safety and tolerability of treatment with resveratrol will be assessed by analysis of adverse events, including symptoms, abnormal findings on physical examinations, standard laboratory tests and PK analysis of resveratrol and its major metabolites. The frequencies of adverse events or laboratory abnormalities between the participants who receive resveratrol and those receiving placebo will be compared.
Baseline, Weeks 6, 13, 19, 26, 32, 39, 45, and 52
Change From Baseline in Volumetric Magnetic Resonance Imaging (MRI)
Time Frame: Baseline and Week 52
MRI will be used to assess the effect of treatment on rate of whole brain volume
Baseline and Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
Time Frame: Week 52
The ADCS-ADL is an activities of daily living inventory developed by the ADCS to assess functional performance in participants with AD. The ADCS-ADL includes some items from traditional basic ADL tests (e.g., grooming, dressing, walking, bathing, feeding, toileting) as well as instrumental (complex) activities of daily living (e.g., shopping, preparing meals, using household appliances, keeping appointments, reading). This structured questionnaire is administered to the subject's caregiver/study partner. The range of this instrument is 0 to 78 with lower numbers indicating greater impairment.
Week 52
Comparison of the Response to Treatment of Resveratrol Based on ApoE Genotype
Time Frame: Week 52
CSF Abeta40
Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alzheimer's Disease Cooperative Study (ADCS)

Collaborators

National Institute on Aging (NIA)

Investigators

  • Study Director: Raymond S. Turner, MD, PhD, Georgetown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

December 23, 2011

First Submitted That Met QC Criteria

January 3, 2012

First Posted (Estimate)

January 6, 2012

Study Record Updates

Last Update Posted (Estimate)

June 14, 2016

Last Update Submitted That Met QC Criteria

May 6, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADC-037-RES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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