Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
- Registration Number
- NCT06463743
- Lead Sponsor
- State University of New York at Buffalo
- Brief 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
- Detailed Description
Specific aims and rationale:
The main aim of this study is to determine the safety of metformin as monotherapy or as an add-on therapy to the disease modifying treatment in aging people with multiple sclerosis (pwMS). While the tolerability of metformin has been studies in the general population, data specific to the MS population is not currently available. Moreover, understanding the gastrointestinal tolerability of metformin when added on MS disease modifying treatment is needed. Secondly, the study aims at understating the potential neuroprotective properties of metformin as measured through magnetic resonance spectroscopy and change in N-acetyl-aspartate (NAA) levels over a 9-month study period. This pilot study will provide valuable insights into the efficacy and safety of add-on or monotherapy metformin therapy as a potential therapeutic approach to address the complex pathophysiology of MS and offer new avenues for promoting neuroprotection along with potential support for neural repair and remyelination in individuals with this debilitating condition. Previous pre-clinical studies have shown that metformin can promote neuroprotection by reducing oxidative stress and inflammation and is able to enhance the reparative mechanisms within the central nervous system (CNS). Currently there are no neuroprotective interventions available for pwMS that directly target the neurodegenerative component of MS, with particular emphasis for the aging MS population. The investigators hypothesize that older pwMS that are treated with metformin will have a significantly lower decline in N-acetylaspartate levels when compared to pwMS not treated with metformin.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
- age between 55 and 75 years old
- having a diagnosis of MS based on the latest McDonald criteria
- non-active disease course (no relapses and no MRI activity) in the last 2 years as determined by the MS provider and based on the 2020 revised clinical course criteria
- EDSS score <7.0
- inability to undergo MRI scans
- inability to participate in the study during the study period
- diabetes or uncontrolled cardiovascular disease
- unable to consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo Placebo placebo metformin metformin metformin
- Primary Outcome Measures
Name Time Method Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. 1 year 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 recordedPercent change in N-Acetyl Aspartate (NAA) in the cortex over 9 months 9 months The MRI scans will be acquired at baseline and 9-month follow-up using magnetic resonance spectroscopy (MRS).
- Secondary Outcome Measures
Name Time Method Brief Visuospatial Memory Test ( BVMT) 1 year correct number of figures out of 6 - immediate and delayed after 20 min
Conventional MRI outcomes 9 months Conventional MRI metrics: lesion burden: number and volume of lesions
9-hole peg test (9HPT) 1 year 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
Symbol Digit Modality Test (SDMT) 1 year 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.California Verbal Learning Test (CVLT) 1 year Number of words remembered immediate and delayed out of a list of 16 words- (max is 16)
Timed 25-foot walk test (T25FWT) 1 year Eval of gait, Change of 20% in the T25FWT (seconds) represents a meaningful change
Disability progression as measured with Expanded Disability Status Scale (EDSS) 1 year 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.
Myelin water fraction (MWF) 9 months Non-conventional MRI metrics : myelin water fraction (MWF)