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Metformin in Amnestic Mild Cognitive Impairment (MCI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00620191
Recruitment Status : Completed
First Posted : February 21, 2008
Last Update Posted : March 14, 2013
Institute for the Study of Aging (ISOA)
National Institute on Aging (NIA)
Information provided by (Responsible Party):
José A. Luchsinger, Columbia University

Brief Summary:
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 (total recall of the Selective Reminding Test) and the Score a test of general cognitive function used in clinical trials (the Alzheimer's Disease Assessment Scale-cognitive subscale-ADAS-Cog). . Another aim is to compare brain function in an area affected by Alzheimer's disease between the metformin and placebo group mean changes from beginning to end among 40 participants using a PET scan.

Condition or disease Intervention/treatment Phase
Amnestic Mild Cognitive Impairment Drug: metformin Drug: placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Metformin in the Prevention of Alzheimer's Disease
Study Start Date : February 2008
Actual Primary Completion Date : February 2012
Actual Study Completion Date : February 2012

Arm Intervention/treatment
Placebo Comparator: P
placebo identical to metformin.
Drug: placebo
placebo identical to metformin 2 tablets twice a day titrated from one table once a day

Experimental: metformin
metformin 1000 mg twice a day
Drug: metformin
metformin 1000 mg twice a day titrated from 500 mg once a day
Other Name: glucophage

Primary Outcome Measures :
  1. Total Recall in the Selective Reminding Test [ Time Frame: 12 MONTHS ]
  2. ADAS-cog [ Time Frame: 12 months ]
    Alzheimer's Disease Assessment Scale-cognitive subscale

Secondary Outcome Measures :
  1. rCMRgl in the posterior cingulate-precuneus. [ Time Frame: 12 months ]
    Change in relative glucose uptake (rCMRgl) in the posterior cingulate-precuneus measured with subscale (ADAS-Cog). The secondary outcome was brain [18]F-labeled 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET).

Other Outcome Measures:
  1. Plasma Amyloid beta-42 [ Time Frame: 12 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 or diabetes that has never been treated with medications. If diabetes is diagnosed during screening or they have a history of diabetes not treated in the last 12 months they will be excluded if their HbA1c is > 6.5.
  • 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.
  • We will also exclude subjects with a history of intolerance to metformin.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00620191

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United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Institute for the Study of Aging (ISOA)
National Institute on Aging (NIA)
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Principal Investigator: Jose A Luchsinger, MD Columbia University

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Responsible Party: José A. Luchsinger, Associate Professor of Medicine and Epidemiology at NYPH/CUMC, Columbia University Identifier: NCT00620191    
Other Study ID Numbers: AAAC7231
R0153596 ( Other Grant/Funding Number: NIA )
First Posted: February 21, 2008    Key Record Dates
Last Update Posted: March 14, 2013
Last Verified: March 2013
Keywords provided by José A. Luchsinger, Columbia University:
mild cognitive impairment
alzheimer's disease
Additional relevant MeSH terms:
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Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Hypoglycemic Agents
Physiological Effects of Drugs