Metformin in Amnestic Mild Cognitive Impairment (MCI)

This study has been completed.
Sponsor:
Collaborators:
Institute for the Study of Aging (ISOA)
Information provided by (Responsible Party):
José A. Luchsinger, Columbia University
ClinicalTrials.gov Identifier:
NCT00620191
First received: February 7, 2008
Last updated: March 13, 2013
Last verified: March 2013
  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 (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 Intervention Phase
Amnestic Mild Cognitive Impairment
Drug: metformin
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Metformin in the Prevention of Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Total Recall in the Selective Reminding Test [ Time Frame: 12 MONTHS ] [ Designated as safety issue: No ]
  • ADAS-cog [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Alzheimer's Disease Assessment Scale-cognitive subscale


Secondary Outcome Measures:
  • rCMRgl in the posterior cingulate-precuneus. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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:
  • Plasma Amyloid beta-42 [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: February 2008
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: placebo
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

  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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00620191

Locations
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)
Investigators
Principal Investigator: Jose A Luchsinger, MD Columbia University
  More Information

Publications:
Responsible Party: José A. Luchsinger, Associate Professor of Medicine and Epidemiology at NYPH/CUMC, Columbia University
ClinicalTrials.gov Identifier: NCT00620191     History of Changes
Other Study ID Numbers: AAAC7231, R0153596
Study First Received: February 7, 2008
Last Updated: March 13, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
Mild Cognitive Impairment
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014