PHASE II STUDY TO EVALUATE THE IMPACT ON BIOMARKERS OF RESVERATROL TREATMENT IN PATIENTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE

Study ID
STU 122011-077

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

Contact
Jacqueline Rabb
214-648-9376
jackie.rabb@utsouthwestern.edu

Principal Investigator
Mary Quiceno

Summary

a double blind, placebo-controlled trial will be conducted by recruitment at approximately 25 sites within the united States. one hundred twenty (120) subjects with mild to moderate dementia due to probable alzheimer's disease will be randomly assigned to treatment 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 CSF at Baseline and at Week 52. Participants will undergo an MRi 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 Bun and Cr, PK analyses for resveratrol and its metabolites, and urinalysis every 6-7 weeks during the study.

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 (to be performed at selected clinical sites). This site is not participating in the PK analysis.

Primary objectives are:
1. To assess the effect of a stepped dose treatment of resveratrol on putative biomarkers of alzheimer's disease (aD) (particularly CSF total tau, but also CSF abeta42, CSF abeta40, and CSF phospho-tau181).

2. To assess the safety and tolerability of treatment with resveratrol over a 12-month period in participants with mild to moderate aD as assessed by analysis of adverse events, including symptoms, abnormal findings on physical examinations, neurological examinations, standard laboratory tests and PK analysis of resveratrol and its major metabolites.

3. To assess the effect of a stepped dose treatment of resveratrol on rate of whole-brain and hippocampal atrophy, as well as regional cortical thinning, using volumetric magnetic resonance imaging (MRi).

Primary outcome Measures: CSF total tau, CSF phospho- tau181, abeta40, abeta42, adverse events, Physical examinations, neurological examinations, Clinical Laboratory Results, PK of resveratrol and its metabolites, Rate of whole-brain volume change, Rate of ventricular volume change, Rate of hippocampal volume change, Rate of entorhinal cortex thickness change.

Participant Eligibility

1. Age >=50
2. Fluent in English
3. Able to ingest oral medications
4. Diagnosis of probable AD by NINCDS-ADRDA criteria
5. Neuroimaging consistent with the diagnosis of AD at some time after the onset of the memory decline
6. MMSE between 14 and 26 at Screening, inclusive
7. Modified Hachinski score <=4
8. Caregiver/Study Partner to accompany participant to all visits
9. Study Partner must have direct contact with the participant (MINIMUM OF 10 HOURS PER WEEK) > 2 days/week
10. Supervision available for study medication
11. Stable medical condition for 3 months prior to screening visit
12. Stable medications for 4 weeks prior to screening visit
13. Able to complete baseline assessments
14. Minimum of six years of education, or work history sufficient to exclude mental retardation
15. Able to abstain from ingesting large quantities of resveratrol-containing foods (including red
wine).
16. Able to abstain from ingesting herbal/natural preparations or dietary supplements containing
resveratrol.
17. Stable use of cholinesterase inhibitors and memantine (U.S. FDA-approved medications for
patients with probable AD), vitamin E (up to 2000 IU daily), estrogens, aspirin (81-325 mg 2x
daily), and cholesterol-lowering agents for 3 months prior to screening is allowed.
18. Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator.