Randomized Trial of a Nutritional Supplement in Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Resveratrol with Glucose, and Malate; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Dietary supplement delivered in grape juice; Liquid placebo
Intervention MeSH terms: Resveratrol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Alzheimer's Disease; Dementia; Nutritional Supplement; Resveratrol