Preventing Cognitive Decline With Metformin

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Preventing Cognitive Decline With Metformin:: The MetMemory Study

Conditions
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Cognitive Decline

Intervention / Treatment
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* Drug: Metformin XR, 500-2000mg nocte


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomised placebo controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Metformin | Drug: Metformin XR, 500-2000mg nocte<br>* anti diabetic medication<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Metformin XR, 500-2000mg nocte<br>* anti diabetic medication<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognitive decline, dementia, cerebrovascular disease, insulin resistance, neurodegeneration, inflammation, diabetes