Randomized Trial of a Nutritional Supplement in Alzheimer's Disease
Alzheimer's disease (AD), one of the leading causes of morbidity and mortality in the elderly is characterized by progressive cognitive decline and certain neuropathological features.
Currently, there is great interest in the well-documented mitochondrial (oxidative) lesion in AD. Disturbed oxidative metabolism is a well described abnormality in AD. Several observational studies have shown that moderate consumption of wine is associated with a lower incidence of Alzheimer's disease (Truelsen et al., 2002; Luchsinger et al., 2004). Wine is enriched in antioxidant compounds with potential neuroprotective activities. In the early 1990s the presence of Resveratrol in red wine was detected where it is suspected to afford antioxidant and neuroprotective properties (Miller and Rice-Evans, 1995).
Blass and Gordon (2004) have demonstrated positive effects in AD with an oral preparation of glucose, malate and resveratrol. Glucose is the physiological precursor of the substrates of oxidative metabolism in the brain, malate is a primer of the energy-providing Krebs-cycle. Glucose and malate therefore can provide reducing equivalents (electrons) to regenerate the reduced form of resveratrol, and do so under the normal regulation of brain cell metabolism. All three ingredients are classified by the FDA as Generally Recognized As Safe.
|Alzheimer's Disease||Dietary Supplement: Resveratrol with Glucose, and Malate Dietary Supplement: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Single Center, Multi-site, Randomized, Double-blind, Placebo-controlled Trial of Resveratrol With Glucose and Malate (RGM) to Slow the Progression of Alzheimer's Disease|
- Alzheimer Disease Assessment Scale (ADAScog) [ Time Frame: one year ]
- CGIC [ Time Frame: one year ]
|Study Start Date:||January 2008|
|Study Completion Date:||June 2011|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Placebo Comparator: Arm 1
Dietary Supplement: Placebo
Experimental: Arm 2
Liquid Resveratrol with Glucose, and Malate
Dietary Supplement: Resveratrol with Glucose, and Malate
Dietary supplement delivered in grape juice
Subjects will be assessed by their capacity to consent by a psychiatrist independent of this study. Subjects who are determined to have capacity will sign consent. For subjects determined to lack capacity consent will be obtained from their surrogate. Subjects lacking in capacity must nonetheless provide verbal assent to participation in this study. After informed consent is obtained, subjects will be screened for eligibility to participate in the study. Screening comprises of medical history, physical exam, neurological exam, and a MMSE.
All of the above are performed for research purposes. Further evaluation of medical problems that are identified in the course of screening will be obtained as part of standard clinical care. For example, if an abnormality requiring further evaluation is detected on blood tests the subsequent evaluation will be conducted as standard clinical care.
Subjects who meet eligibility criteria will be baseline within 4 weeks. Eligible subjects will not be asked to stop any medication they may currently be on before the study begins. Eligible subjects will be randomized to receive either a mixture of glucose, malate and resveratrol (RGM) or placebo. At baseline, medical history, physical exam, cognitive tests are obtained. An ECG and a panel consisting CBC, electrolytes, liver and renal function tests will be drawn at the screening visit. Clinical information is obtained from the identified caregiver. The study drug (RGM or placebo, depending on which group the subject is randomly assigned to) is dispensed at baseline. Follow up visits at months 3, 6, 9, and 12 months require physical exam and some cognitive measures. At Month 12 a neurological exam will be performed. Adverse events are collected at each visit. Medication compliance is assessed at months 3, 6, 9, and 12 months and unused study drug is retrieved. At Month 12 unused study drug is retrieved and no more study drug is dispensed. Clinical information is obtained from the caregiver at each visit. At the Month 12 visit, a questionnaire will be completed by the study staff, subject and study partner to assess the adequacy of medication blinding. As noted all of the above tests and procedures are part of the research protocol. At study termination the subject will be referred to ongoing clinical care as appropriate.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00678431
|United States, New York|
|James J. Peters VA Medical Center, Bronx, NY|
|Bronx, New York, United States, 10468|
|Principal Investigator:||Mary Sano, PhD||VA Office of Research and Development|