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Randomized Trial of a Nutritional Supplement in Alzheimer's Disease

This study has been completed.
Sponsor:
Collaborators:
Alzheimer's Association
Mount Sinai School of Medicine
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00678431
First received: January 7, 2008
Last updated: November 13, 2012
Last verified: November 2012

January 7, 2008
November 13, 2012
January 2008
December 2010   (final data collection date for primary outcome measure)
Alzheimer Disease Assessment Scale (ADAScog) [ Time Frame: one year ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00678431 on ClinicalTrials.gov Archive Site
CGIC [ Time Frame: one year ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Randomized Trial of a Nutritional Supplement in Alzheimer's Disease
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'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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Alzheimer's Disease
  • Dietary Supplement: Resveratrol with Glucose, and Malate
    Dietary supplement delivered in grape juice
  • Dietary Supplement: Placebo
    Liquid placebo
  • Placebo Comparator: Arm 1
    Liquid placebo
    Intervention: Dietary Supplement: Placebo
  • Experimental: Arm 2
    Liquid Resveratrol with Glucose, and Malate
    Intervention: Dietary Supplement: Resveratrol with Glucose, and Malate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
27
June 2011
December 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Consenting individuals as defined by IRB guidelines
  2. NINCDS/ADRDA criteria for probable AD
  3. Community dwelling
  4. Age: greater than or equal to 50 years
  5. MMSE between 12 and 26, inclusive
  6. Stable medical condition for 3 months prior to screening visit
  7. Stable doses of (non excluded) medications with central nervous system activity for 4 weeks prior to the screening visit (For cholinesterase inhibitors there should be no plan of dose escalation)
  8. Physically acceptable for this study as confirmed by medical history, physical exam, neurologic exam and clinical laboratory tests
  9. Supervision available for administration of study medications
  10. Study partner to accompany subject to all scheduled visits and complete informant-based assessments.
  11. Fluent in English or Spanish
  12. Modified Hachinski < 4
  13. CT or MRI since onset of memory impairment demonstrating absence of clinically significant focal lesion (One lacune in a non-critical brain region is acceptable)
  14. Able to complete baseline assessments
  15. 6 years of education, or work history sufficient to exclude mental retardation
  16. Able to ingest oral medication

Exclusion Criteria:

  1. Active liver disease or persistent elevation in serum transaminase
  2. Severe renal disease
  3. - Hx of diabetes mellitus (both insulin-dependent and non-insulin-dependent) or blood glucose >150 mg/dl
  4. Active neoplastic disease (skin tumors other than melanoma are not exclusionary; subjects with stable prostate cancer or other stable cancers may be included at the discretion of the PI (Sano))
  5. Use of another investigational agent within 2 months of the screening visit
  6. History of clinically significant stroke
  7. Current evidence or history in the past 2 years of seizures, head injury with loss of consciousness and/or immediate confusion after the injury
  8. Current DSM-IV criteria-based diagnosis for major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse.
  9. Blindness, deafness, language difficulties or any other disability which may interfere with testing ability
  10. In female subjects, no history of menopause
  11. Use of medications containing aluminum hydroxide, including anti-ulcer antacids such as Alternagel, Amphojel, Alu-tab, Maalox and Mylanta
Both
50 Years to 90 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00678431
0553-06-071
No
Department of Veterans Affairs
Department of Veterans Affairs
  • Alzheimer's Association
  • Mount Sinai School of Medicine
Principal Investigator: Mary Sano, PhD Department of Veterans Affairs
Department of Veterans Affairs
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP