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Metformin in Amnestic Mild Cognitive Impairment (MCI)
This study is currently recruiting participants.
Verified by Columbia University, November 2008
Sponsors and Collaborators: Columbia University
Institute for the Study of Aging (ISOA)
National Institute on Aging (NIA)
Information provided by: Columbia University
ClinicalTrials.gov Identifier: NCT00620191
  Purpose

Hyperinsulinemia and type 2 diabetes (T2D) are important potential risk factors for cognitive decline and Alzheimer's disease (AD). Two thirds of the US adult population are at risk for hyperinsulinemia and T2D, and half of the population 85 years and older have AD. Peripheral hyperinsulinemia can impair the clearance of amyloid beta in the brain, the main culprit in AD. Thus, we hypothesize the lowering peripheral insulin in overweight persons with amnestic mild cognitive impairment (AMCI), a transition state between normal cognition and AD, can decrease the risk of cognitive decline and progression to AD. We propose to conduct a phase II double blinded placebo controlled randomized clinical trial of metformin, a safe and effective medication that prevents hyperinsulinemia and diabetes, to test this hypothesis among 80 overweight persons aged 55 to 90 years with AMCI. The main outcome of the study will be changes in performance in a memory test and in a composite score of cognition and function. Another aim is to compare brain imaging on an intention-to-treat basis between the metformin and placebo group mean changes from beginning to end among 40 participants using FDG PET scan and MRI.


Condition Intervention Phase
Amnestic Mild Cognitive Impairment
Drug: metformin
Drug: placebo
Phase II

Genetics Home Reference related topics: Alzheimer disease
MedlinePlus related topics: Alzheimer's Disease Diabetes
Drug Information available for: Insulin Metformin Metformin hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title: Metformin in the Prevention of Alzheimer's Disease

Further study details as provided by Columbia University:

Primary Outcome Measures:
  • ADAS-COG [ Time Frame: 12 MONTHS ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • plasma amyloid beta [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: February 2008
Estimated Study Completion Date: January 2010
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
P: Placebo Comparator
placebo identical to metformin.
Drug: placebo
placebo identical to metformin 2 tablets twice a day titrated from one table once a day
metformin: Experimental
metformin 1000 mg twice a day
Drug: metformin
metformin 1000 mg twice a day titrated from 500 mg once a day

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   55 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age range: 55 to 90 years;
  • Sex distribution: men and women;
  • Languages: fluent in English or Spanish.
  • Subjects must score below a pre-determined cut-off score on the logical memory II delayed paragraph recall sub-test of the Wechsler Memory Scale Revised (WMS-R)26:

    1. less than or equal to 8 for 16 or more years of education.;
    2. less than or equal to 4 for 8-15 years of education;
    3. less than or equal to 2 for 0-7 years of education.
  • Global Clinical dementia rating (CDR) score must be 0.5 at screening. The memory box score must be 0.5 or 1.0, with no more than two box scores other than memory rated as high as 1.0 and no box score rated greater than 1.0.
  • Subjects without a known history of diabetes. If diabetes is diagnosed during screening they will also be excluded. The justification for this exclusion is the potential for these subjects to be placed on other diabetes medications that may confound our study.
  • BMI ≥ 25 kg/m2
  • No contraindications to metformin treatment.
  • General cognition and functional performance such that a diagnosis of dementia cannot be made at the time of screening based on DSM-IV criteria.
  • Vision and hearing must be sufficient for compliance with testing procedures.

Exclusion Criteria:

  • Subjects with uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg;
  • Subjects with a history of active cancer or cancer within last five years, with the exception of squamous or basal cell carcinoma of the skin;
  • Subjects who for any reason may not complete the study as judged by the study physician;
  • Abnormal TSH, B12, and RPR.
  • Contraindications to metformin use include a creatinine of > 1.5, liver disease by history or by elevated transaminases, congestive heart failure, and alcohol abuse 11, 20, 27.
  • We will also exclude subjects with a history of intolerance to metformin.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00620191

Contacts
Contact: Jose A Luchsinger, MD 212-3054730 jal94@columbia.edu

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Alex R Sierra, BA     212-305-4126     as2903@columbia.edu    
Contact: Evelyn Arana, MS     646 584 1166     ea2310@columbia.edu    
Principal Investigator: Jose A Luchsinger, MD            
Sponsors and Collaborators
Columbia University
Institute for the Study of Aging (ISOA)
Investigators
Principal Investigator: Jose A Luchsinger, MD Columbia University Medical Center
  More Information

Publications:
Responsible Party: Columbia University Medical Center ( Jose Luchsinger )
Study ID Numbers: ISOA270901, AAAC7231
Study First Received: February 7, 2008
Last Updated: November 17, 2008
ClinicalTrials.gov Identifier: NCT00620191  
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
metformin
mild cognitive impairment
alzheimer's disease
overweight
insulin

Study placed in the following topic categories:
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Metformin
Alzheimer Disease
Central Nervous System Diseases
Overweight
Neurodegenerative Diseases
Brain Diseases
Dementia
Insulin
Cognition Disorders
Delirium

Additional relevant MeSH terms:
Hypoglycemic Agents
Physiological Effects of Drugs
Nervous System Diseases
Tauopathies
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009