Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)

University at Buffalo (UB)

Status and phase: Begins enrollment in 2 months; Phase 2

Conditions: Multiple Sclerosis

Treatments: Drug: metformin; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06463743

UL1TR001412 (U.S. NIH Grant/Contract)

STUDY00007603

Details and patient eligibility

About

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

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 55 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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30 participants in 2 patient groups, including a placebo group

metformin

Experimental group

Description:

metformin

Treatment:

Drug: metformin

placebo

Placebo Comparator group

Description:

placebo

Treatment:

Drug: Placebo