Trial Outcomes & Findings for Resveratrol for Alzheimer's Disease (NCT NCT01504854)

Last Updated: 2016-06-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

119 participants

Primary outcome timeframe

Baseline, Weeks 6, 13, 19, 26, 32, 39, 45, and 52

Results posted on

2016-06-14

Participant Flow

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).

119 subjects were recruited rather than 120.

Participant milestones

Participant milestones
Measure	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. 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 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 Study STARTED	64	55
Overall Study COMPLETED	56	48
Overall Study NOT COMPLETED	8	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Resveratrol for Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Resveratrol n=64 Participants 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).	Placebo n=55 Participants 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 n=119 Participants Total of all reporting groups
Age, Continuous	69.8 years STANDARD_DEVIATION 7.7 • n=39 Participants	73 years STANDARD_DEVIATION 8.2 • n=41 Participants	71.4 years STANDARD_DEVIATION 7.95 • n=35 Participants
Sex: Female, Male Female	40 Participants n=39 Participants	28 Participants n=41 Participants	68 Participants n=35 Participants
Sex: Female, Male Male	24 Participants n=39 Participants	27 Participants n=41 Participants	51 Participants n=35 Participants

PRIMARY outcome

Timeframe: Baseline, Weeks 6, 13, 19, 26, 32, 39, 45, and 52

Population: ITT population

Outcome measures

Outcome measures
Measure	Resveratrol n=56 Participants 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).	Placebo n=48 Participants 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.
Number of Adverse Events	355 number of AEs	302 number of AEs

PRIMARY outcome

Timeframe: Baseline and Week 52

Population: ITT population

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

Outcome measures

Outcome measures
Measure	Resveratrol n=56 Participants 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).	Placebo n=48 Participants 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.
Change From Baseline in Volumetric Magnetic Resonance Imaging (MRI)	27 cm^3 Standard Deviation 12	10 cm^3 Standard Deviation 7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Resveratrol n=56 Participants 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).	Placebo n=48 Participants 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.
Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)	6.3 units on a scale Standard Deviation 11.6	9.2 units on a scale Standard Deviation 12.6

SECONDARY outcome

Timeframe: Week 52

Population: ITT analyses. Total population and subpopulation of ApoE4 non-carriers.

CSF Abeta40

Outcome measures

Outcome measures
Measure	Resveratrol n=56 Participants 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).	Placebo n=48 Participants 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.
Comparison of the Response to Treatment of Resveratrol Based on ApoE Genotype ApoE4 non-carriers	5859 ng/ml Standard Deviation 2085	6339 ng/ml Standard Deviation 1709
Comparison of the Response to Treatment of Resveratrol Based on ApoE Genotype Total Population	6574 ng/ml Standard Deviation 2346	6560 ng/ml Standard Deviation 2190

POST_HOC outcome

Timeframe: Baseline and Week 52

Population: 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

Mean change from baseline in cerebrospinal fluid amyloid β40 concentration at 52 weeks

Outcome measures

Outcome measures
Measure	Resveratrol n=56 Participants 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).	Placebo n=48 Participants 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.
Change From Baseline in Cerebrospinal Fluid Amyloid β40 Concentration at 52 Weeks	6456 ng/ml Standard Deviation 2282	5622 ng/ml Standard Deviation 1736

Adverse Events

Resveratrol

Serious events: 13 serious events

Other events: 64 other events

Deaths: 0 deaths

Placebo

Serious events: 10 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Resveratrol n=64 participants at risk 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).	Placebo n=55 participants at risk 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.
Gastrointestinal disorders Diarrhoea	40.6% 26/64 • Number of events 26 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.	12.7% 7/55 • Number of events 7 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.
Infections and infestations Urinary Tract Infection	29.7% 19/64 • Number of events 19 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.	12.7% 7/55 • Number of events 7 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.
Injury, poisoning and procedural complications Fall	34.4% 22/64 • Number of events 22 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.	25.5% 14/55 • Number of events 14 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.
Nervous system disorders Dizzyness	9.4% 6/64 • Number of events 6 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.	9.1% 5/55 • Number of events 5 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.
Nervous system disorders Headache	17.2% 11/64 • Number of events 11 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.	10.9% 6/55 • Number of events 6 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.
Psychiatric disorders Anxiety	4.7% 3/64 • Number of events 3 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.	9.1% 5/55 • Number of events 5 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.
Skin and subcutaneous tissue disorders Rash	1.6% 1/64 • Number of events 1 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.	12.7% 7/55 • Number of events 7 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.
Vascular disorders Hypertension	6.2% 4/64 • Number of events 4 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.	5.5% 3/55 • Number of events 3 • Adverse event data were collected over a 52 week period (the duration of the subject's participation in the study). 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.

Additional Information

Michael Rafii, MD, PhD

Alzheimer's Disease Cooperative Study

Phone: 858-846-1300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place