Clinical trial NCT06463743: Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
Official title: Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS): Randomized, Placebo-controlled Pilot Study.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: metformin
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2024-06-18
Enrollment: 30
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. age between 55 and 75 years old
2. having a diagnosis of MS based on the latest McDonald criteria
3. 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
4. EDSS score \<7.0

Exclusion Criteria:

1. inability to undergo MRI scans
2. inability to participate in the study during the study period
3. diabetes or uncontrolled cardiovascular disease
4. unable to consent

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
timeFrame: 1 year
measure: Percent change in N-Acetyl Aspartate (NAA) in the cortex over 9 months
timeFrame: 9 months
Secondary outcomes:
measure: Disability progression as measured with Expanded Disability Status Scale (EDSS)
timeFrame: 1 year
measure: Symbol Digit Modality Test (SDMT)
timeFrame: 1 year
measure: Brief Visuospatial Memory Test ( BVMT)
timeFrame: 1 year
measure: California Verbal Learning Test (CVLT)
timeFrame: 1 year
measure: Conventional MRI outcomes
timeFrame: 9 months
measure: Timed 25-foot walk test (T25FWT)
timeFrame: 1 year
measure: 9-hole peg test (9HPT)
timeFrame: 1 year
measure: Myelin water fraction (MWF)
timeFrame: 9 months
Other outcomes:
measure: Exploratory/tertiary MRI metrics
timeFrame: 9 months
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