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Resveratrol for Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT01504854
Recruitment Status : Completed
First Posted : January 6, 2012
Results First Posted : June 14, 2016
Last Update Posted : June 14, 2016
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Alzheimer's Disease Cooperative Study (ADCS)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: Resveratrol
Drug: Placebo
Enrollment 119
Recruitment Details A multicenter, double-blind, placebo-controlled trial was conducted June 2012–March 2014 with participants recruited from 26 US academic clinics affiliated with the Alzheimer’s Disease Cooperative Study (ADCS).
Pre-assignment Details 119 subjects were recruited rather than 120.
Arm/Group Title Resveratrol Placebo
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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.

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).

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

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

Period Title: Overall Study
Started 64 55
Completed 56 48
Not Completed 8 7
Arm/Group Title Resveratrol Placebo Total
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60 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.

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).

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

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

Total of all reporting groups
Overall Number of Baseline Participants 64 55 119
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 64 participants 55 participants 119 participants
69.8  (7.7) 73  (8.2) 71.4  (7.95)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 55 participants 119 participants
Female
40
  62.5%
28
  50.9%
68
  57.1%
Male
24
  37.5%
27
  49.1%
51
  42.9%
1.Primary Outcome
Title Number of Adverse Events
Hide Description 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.
Time Frame Baseline, Weeks 6, 13, 19, 26, 32, 39, 45, and 52
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Hide Analysis Population Description
ITT population
Arm/Group Title Resveratrol Placebo
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60 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.

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).

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

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

Overall Number of Participants Analyzed 56 48
Measure Type: Number
Unit of Measure: number of AEs
355 302
2.Primary Outcome
Title Change From Baseline in Volumetric Magnetic Resonance Imaging (MRI)
Hide Description MRI will be used to assess the effect of treatment on rate of whole brain volume
Time Frame Baseline and Week 52
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Hide Analysis Population Description
ITT population
Arm/Group Title Resveratrol Placebo
Hide Arm/Group Description:

60 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.

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).

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

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

Overall Number of Participants Analyzed 56 48
Mean (Standard Deviation)
Unit of Measure: cm^3
27  (12) 10  (7)
3.Secondary Outcome
Title Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
Hide Description 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.
Time Frame Week 52
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Resveratrol Placebo
Hide Arm/Group Description:

60 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.

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).

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

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

Overall Number of Participants Analyzed 56 48
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.3  (11.6) 9.2  (12.6)
4.Secondary Outcome
Title Comparison of the Response to Treatment of Resveratrol Based on ApoE Genotype
Hide Description CSF Abeta40
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analyses. Total population and subpopulation of ApoE4 non-carriers.
Arm/Group Title Resveratrol Placebo
Hide Arm/Group Description:

60 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.

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).

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

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

Overall Number of Participants Analyzed 56 48
Mean (Standard Deviation)
Unit of Measure: ng/ml
Total Population 6574  (2346) 6560  (2190)
ApoE4 non-carriers 5859  (2085) 6339  (1709)
5.Post-Hoc Outcome
Title Change From Baseline in Cerebrospinal Fluid Amyloid β40 Concentration at 52 Weeks
Hide Description Mean change from baseline in cerebrospinal fluid amyloid β40 concentration at 52 weeks
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Post-hoc modified intention-to-treat (ITT) re-analysis of primary outcomes at Week 52 adjusting for age and AD duration in the mixed-model repeated measures model
Arm/Group Title Resveratrol Placebo
Hide Arm/Group Description:

60 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.

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).

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

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

Overall Number of Participants Analyzed 56 48
Mean (Standard Deviation)
Unit of Measure: ng/ml
6456  (2282) 5622  (1736)
Time Frame Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study).
Adverse Event Reporting Description Participants received physical and neurologic examinations and vital signs at each visit. Site investigators classified AEs by severity and causality. If a participant withdrew, an early termination visit similar to a baseline visit was scheduled. An independent Data and Safety Monitoring Board reviewed data quarterly.
 
Arm/Group Title Resveratrol Placebo
Hide Arm/Group Description

60 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.

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).

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

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

All-Cause Mortality
Resveratrol Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Resveratrol Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/64 (20.31%)      10/55 (18.18%)    
Cardiac disorders     
Congestive heart failure  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Syncope/atrial fibrillation  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Gastrointestinal disorders     
Perforated viscus with perforated sigmoid diverticulitis with peritonitis  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Hiatal hernia  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Infections and infestations     
Pneumonia  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Urinary tract infection  1  1/64 (1.56%)  1 1/55 (1.82%)  1
Infections  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Injury, poisoning and procedural complications     
Fall  1  2/64 (3.13%)  2 1/55 (1.82%)  1
Drowning  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Left femoral neck fracture  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Complications from colostomy reversal  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Investigations     
Low hemoglobin  1  0/64 (0.00%)  0 2/55 (3.64%)  2
Metabolism and nutrition disorders     
Water intoxication  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Hypokalemia  1  2/64 (3.13%)  2 0/55 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Rhabdomyolosis  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Melanoma of the lung, Stage 4  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Large pleural effusion secondary to stage 4 melanoma of the lung  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Bladder tumor  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Malignant glioma  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Nervous system disorders     
Seizure  1  2/64 (3.13%)  2 0/55 (0.00%)  0
Syncope  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Subdural hematoma  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Unresponsiveness  1  0/64 (0.00%)  0 1/55 (1.82%)  1
Altered mental state  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Altered mental state  1  1/64 (1.56%)  2 1/55 (1.82%)  1
Respiratory, thoracic and mediastinal disorders     
Difficulty breathing  1  0/64 (0.00%)  0 1/55 (1.82%)  1
"Blood clots" in the lung/pulmonary embolism  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Vascular disorders     
Right peripheral vascular disease (status post Carotid Endarterectomy)  1  1/64 (1.56%)  1 0/55 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Resveratrol Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   64/64 (100.00%)      52/55 (94.55%)    
Gastrointestinal disorders     
Diarrhoea  1  26/64 (40.63%)  26 7/55 (12.73%)  7
Infections and infestations     
Urinary Tract Infection  1  19/64 (29.69%)  19 7/55 (12.73%)  7
Injury, poisoning and procedural complications     
Fall  1  22/64 (34.38%)  22 14/55 (25.45%)  14
Nervous system disorders     
Dizzyness  1  6/64 (9.38%)  6 5/55 (9.09%)  5
Headache  1  11/64 (17.19%)  11 6/55 (10.91%)  6
Psychiatric disorders     
Anxiety  1  3/64 (4.69%)  3 5/55 (9.09%)  5
Skin and subcutaneous tissue disorders     
Rash  1  1/64 (1.56%)  1 7/55 (12.73%)  7
Vascular disorders     
Hypertension  1  4/64 (6.25%)  4 3/55 (5.45%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Michael Rafii, MD, PhD
Organization: Alzheimer's Disease Cooperative Study
Phone: 858-846-1300
Responsible Party: Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier: NCT01504854     History of Changes
Other Study ID Numbers: ADC-037-RES
First Submitted: December 23, 2011
First Posted: January 6, 2012
Results First Submitted: January 28, 2016
Results First Posted: June 14, 2016
Last Update Posted: June 14, 2016