Resveratrol for Alzheimer's Disease

NCT01504854 | Completed Phase 2 Results DMC

• 1 other identifier: ADC-037-RES
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 26

Brief Summary

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.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease; Dementia; Brain diseases; Resveratrol; Memory problems; Mental disorders; Cognitive disorders

Outcome Measures

Primary Outcomes (2)

• Number of Adverse Events

  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)

  MRI will be used to assess the effect of treatment on rate of whole brain volume

  Baseline and Week 52

Secondary Outcomes (2)

• Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)

  Week 52

• Comparison of the Response to Treatment of Resveratrol Based on ApoE Genotype

  Week 52

Study Arms (2)

Resveratrol

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Subjects will receive a matching placebo to be taken with or without food.

Drug: Placebo

Interventions

Resveratrol DRUG

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).

Resveratrol

Placebo DRUG

The matching placebo will begin at a capsule taken once daily and increase at 13 week intervals to two capsules twice daily.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alzheimer's Disease Cooperative Study (ADCS): lead
• National Institute on Aging (NIA): collaborator

Study Sites (26)

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

University of California, San Diego - Comprehensive Alzheimer's Program

La Jolla, California, 92037, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Howard University

Washington D.C., District of Columbia, 20060, United States

Location

Mayo Clinic, Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Kansas

Kansas City, Kansas, 66205, United States

Location

University of Kentucky

Lexington, Kentucky, 40504, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Mayo Clinic, Rochester

Rochester, Minnesota, 55905, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 89106, United States

Location

New York University

New York, New York, 10016, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14620, United States

Location

Case Western Reserve University

Beachwood, Ohio, 44122, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

North Charleston, South Carolina, 29406, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

U of WA / VA Puget Sound Alzheimer's Disease Research Center

Seattle, Washington, 98108, United States

Location

Related Publications (8)

• Vang O, Ahmad N, Baile CA, Baur JA, Brown K, Csiszar A, Das DK, Delmas D, Gottfried C, Lin HY, Ma QY, Mukhopadhyay P, Nalini N, Pezzuto JM, Richard T, Shukla Y, Surh YJ, Szekeres T, Szkudelski T, Walle T, Wu JM. What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS One. 2011;6(6):e19881. doi: 10.1371/journal.pone.0019881. Epub 2011 Jun 16.

  PMID: 21698226 BACKGROUND

• Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health--a comprehensive review of human clinical trials. Mol Nutr Food Res. 2011 Aug;55(8):1129-41. doi: 10.1002/mnfr.201100143. Epub 2011 Jun 20.

  PMID: 21688389 BACKGROUND

• Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, Brown K. Clinical trials of resveratrol. Ann N Y Acad Sci. 2011 Jan;1215:161-9. doi: 10.1111/j.1749-6632.2010.05853.x.

  PMID: 21261655 BACKGROUND

• Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, Hoeks J, van der Krieken S, Ryu D, Kersten S, Moonen-Kornips E, Hesselink MKC, Kunz I, Schrauwen-Hinderling VB, Blaak E, Auwerx J, Schrauwen P. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011 Nov 2;14(5):612-22. doi: 10.1016/j.cmet.2011.10.002.

  PMID: 22055504 BACKGROUND

• Albani D, Polito L, Forloni G. Sirtuins as novel targets for Alzheimer's disease and other neurodegenerative disorders: experimental and genetic evidence. J Alzheimers Dis. 2010;19(1):11-26. doi: 10.3233/JAD-2010-1215.

  PMID: 20061622 BACKGROUND

• Greco GA, Rock M, Amontree M, Lanfranco MF, Korthas H, Hong SH, Turner RS, Rebeck GW, Conant K. CCR5 deficiency normalizes TIMP levels, working memory, and gamma oscillation power in APOE4 targeted replacement mice. Neurobiol Dis. 2023 Apr;179:106057. doi: 10.1016/j.nbd.2023.106057. Epub 2023 Mar 5.

  PMID: 36878326 DERIVED

• Stites SD, Turner RS, Gill J, Gurian A, Karlawish J, Grill JD; Alzheimer's Disease Cooperative Study. Research Attitudes Questionnaire scores predict Alzheimer's disease clinical trial dropout. Clin Trials. 2021 Apr;18(2):237-244. doi: 10.1177/1740774520982315. Epub 2021 Jan 10.

  PMID: 33426901 DERIVED

• Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, Turner RS. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease. J Neuroinflammation. 2017 Jan 3;14(1):1. doi: 10.1186/s12974-016-0779-0.

  PMID: 28086917 DERIVED

Related Links

• Alzheimer's Disease Cooperative Study

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Brain Diseases; Memory Disorders; Mental Disorders; Cognitive Dysfunction

Interventions

Resveratrol

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders

Intervention Hierarchy (Ancestors)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols

Limitations and Caveats

This phase 2 study has limitations. A larger study is required to determine whether resveratrol may be beneficial. More potent and bioavailable SIRT1 activators are also in development.

Results Point of Contact

• Title: Michael Rafii, MD, PhD
• Organization: Alzheimer's Disease Cooperative Study

mrafii@ucsd.edu

858-846-1300

Study Officials

• Raymond S. Turner, MD, PhD

  Georgetown University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2011
• First Posted: January 6, 2012
• Study Start: May 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: June 14, 2016
• Results First Posted: June 14, 2016

Record last verified: 2016-04

Locations

US (26)