Preventing Cognitive Decline with Metformin (MetMemory)

Preventing Cognitive Decline with Metformin:: the MetMemory Study

A randomised control study of metformin in people with mild cognitive impairment and without diabetes mellitus to determine effects on cognitive decline and neuroimaging over 3 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Cognitive Decline
• Intervention / Treatment: Drug: Metformin XR, 500-2000mg nocte

Detailed Description

A randomised placebo-control study of metformin in people with mild cognitive impairment and without diabetes mellitus to determine effects on cognitive decline, neuroimaging and biomarkers over 3 years.

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • Garvan Institute of Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• overweight or obese (body mass index >25.0 kg/m2, waist: women>80 cm, men>94cm;
• Mild cognitive impairment (Mild Neurocognitive Disorder), based on DSM-5 criteria;
• Fasting blood glucose <7.0 mmol/L and HbA1c <6.5%;
• Able to undertake neurocognitive testing in English.
• Not participating in another trial of drugs or lifestyle modification to reduce cognitive decline.

Exclusion Criteria:

• Life-threatening illnesses to preclude participation in a 3-year study;
• Contraindications to the use of metformin (severe heart failure or eGFR <40).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Metformin XR, 500-2000mg nocte; Metformin XR, 500-2000mg nocte; Other Names: Placebo
Active Comparator: Intervention; Metformin	Drug: Metformin XR, 500-2000mg nocte; Metformin XR, 500-2000mg nocte; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in memory Z-score	memory domain Z-score, derived from the following neuropsychological tests: i. Rey Auditory Verbal Learning Test (RAVLT); ii. Total Learning and Delayed recall; iii. the Logical Memory Story A- Immediate Recall; and iv. Delayed Recall tests.	3 years
changes in executive function Z-score	executive function domain Z-score, derived from the following neuropsychological tests: i. Alphabet test; ii. D-KEFS Stroop; iii. Trail Making Test Part B; iv. Weschler Adult Intelligence Scale-IV (WAIS-IV) Digit Span Backward test.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in processing speed domain Z-score	processing speed domain measured by the i. WAIS-IV Coding; and ii. Trail Making Test part B	3 years
changes in language performance domain Z-score	language performance domain measured by the Category Fluency (Animals) neuropsychological test	3 years
changes in attention performance domain Z-score	attention performance domain Z-score, measured by the WAIS-IV Digit Span Forward neuropsychological test	3 years
changes in Cogstate brief battery performance Z-score	computerised cognition testing using the on-line test, the Cogstate brief battery (CBB)	3 years
changes in total brain volume (cubic millimetres)	total grey and white matter volume	3 years
changes in hippocampal volume (cubic millimetres)	volume of the right and left hippocampal regions of the brain	3 years
changes in parahippocampal volume (cubic millimetres)	volume of the right and left parahippocampal regions of the brain	3 years
changes in brain white matter hyperintensity number	the number of white matter hyperintensities visualised in bain imaging by magnetic resonance imaging	3 years
changes in cerebral blood flow (mL / 100 g / min)	Cerebral blood flow will be measured using arterial spin labelling	3 years
changes in cerebral amyloid tracer standardized uptake value ratio (SUVR)	standardized uptake value ratio of amyloid tracer using positron emission tomography	3 years
changes in cognitive performance Z-score using the NIH tool box	The NIH Toolbox currently contains the following cognitive tests: Flanker, Pattern Comparison, Picture Sequence Memory and Dimensional Change Card Sort.	3 years
change in BOLD (blood-oxygen-level-dependent) time-series signals measured by functional magnetic resonance imaging	change blood oxygen-level-dependent time-series signals, measured by functional MRI	3 years
changes in biomarkers, including fasting glucose (mmol/L) and insulin (mIU/L), insulin resistance (HOMA-IR index)	fasting glucose (mmol/L) and insulin (mIU/L), insulin resistance (HOMA-IR index)	3 years

Collaborators and Investigators

• Sponsor: Garvan Institute of Medical Research
• Collaborators: National Health and Medical Research Council, Australia

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 2, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: diabetes; dementia; neurodegeneration; inflammation; insulin resistance; cognitive decline; cerebrovascular disease
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 1 (Mobile Health and Wellness Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No