Preventing Cognitive Decline with Metformin

Phase 3

Active, not recruiting

• Conditions: Cognitive Decline
• Interventions: Drug: Metformin XR, 500-2000mg nocte

• Registration Number: NCT04511416
• Lead Sponsor: Garvan Institute of Medical Research

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-07-02
• Study First Submitted QC: 2020-08-10
• Study First Posted: 2020-08-13
• Study Start: 2022-07-15
• Status Verified: 2024-07
• Last Update Submitted: 2024-10-01
• Last Update Posted: 2024-10-02
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 242

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Metformin XR, 500-2000mg nocte	Metformin
Placebo	Metformin XR, 500-2000mg nocte	Placebo

Primary Outcome Measures

Name	Time	Method
changes in memory Z-score	3 years	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.
changes in executive function Z-score	3 years	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Garvan Institute of Medical Research; 🇦🇺 Sydney, New South Wales, Australia