Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
NCT Number: NCT06463743
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Multiple Sclerosis
Interventions: DRUG: metformin|DRUG: Placebo
Sponsor: State University of New York at Buffalo
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 30
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2026-05

Summary:
The goal of the study is to learn about treating older people with multiple sclerosis (MS) with metformin. Metformin may be used as a single therapy or as an add-on therapy. The investigators want to learn:

* The safety and tolerability of metformin extended release (1500 mg/day) as a single therapy or as an add-on therapy in older people with MS compared to placebo
* How well metformin protects the nervous system against injury compared with placebo measured by brain MRI over a 9 month treatment period
* The effect of metformin to protect brain tissue from age and MS related injury when compared to the placebo group over a 9 month treatment period

Primary Outcome Measures: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0., The adverse events (AE) will be collected using standardized Adverse Events Form. The severity of the AE will be determined using 5-level grading system where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE.

Additional information regarding the relation to the study medication (related/non related), treatment required (none/drug/non-drug) and the outcome of the AE will be recorded, 1 year|Percent change in N-Acetyl Aspartate (NAA) in the cortex over 9 months, The MRI scans will be acquired at baseline and 9-month follow-up using magnetic resonance spectroscopy (MRS)., 9 months
Secondary Outcome Measures: Disability progression as measured with Expanded Disability Status Scale (EDSS), Disability quantification using Expanded Disability Status Scale (EDSS) (evaluation performed at baseline, 3, 6 and 9 and 12 months). Disability progression will be determined as an increase of 1.0 points in EDSS if the baseline EDSS is \<5.5 and increase of 0.5 points in EDSS over the follow-up period if baseline EDSS is ≥5.5 points., 1 year|Symbol Digit Modality Test (SDMT), A neuropsychological assessment will be included using the Brief International Cognitive Assessment in MS (BICAMS) battery at baseline, and 9 months.

Within the BICAMS battery, the cognitive performance will be evaluated using the Symbol Digit Modalities Test (SDMT)-measuring the correct number match within 90 sec ( higher is better- over 60 normal) . Group difference of 4-points in the SDMT test will be considered as significantly meaningful cognitive difference between the metformin-treated and placebo group., 1 year|Brief Visuospatial Memory Test ( BVMT), correct number of figures out of 6 - immediate and delayed after 20 min, 1 year|California Verbal Learning Test (CVLT), Number of words remembered immediate and delayed out of a list of 16 words- (max is 16), 1 year|Conventional MRI outcomes, Conventional MRI metrics: lesion burden: number and volume of lesions, 9 months|Timed 25-foot walk test (T25FWT), Eval of gait, Change of 20% in the T25FWT (seconds) represents a meaningful change, 1 year|9-hole peg test (9HPT), 9HPT measured in seconds performed at baseline, 3, 6 and 9 and 12 months. Change of 20% in the 9HPT (seconds) represents a meaningful change, 1 year|Myelin water fraction (MWF), Non-conventional MRI metrics : myelin water fraction (MWF), 9 months
Other Outcome Measures: Exploratory/tertiary MRI metrics, Exploratory/tertiary MRI metrics assessment of cortical lesion burden using synthetic DIR sequence and perfusion-based imaging using arterial spin labeling (ASL)., 9 months