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

Multiple Sclerosis Clinical Trial

Official title:

Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS): Randomized, Placebo-controlled Pilot Study.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06463743
• Other study ID #: STUDY00007603
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 2024
• Est. completion date: May 2026

Study information

• Verified date: June 2024
• Source: State University of New York at Buffalo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: May 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• metformin
metformin
• Placebo
Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
State University of New York at Buffalo

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Brief Visuospatial Memory Test ( BVMT)	correct number of figures out of 6 - immediate and delayed after 20 min	1 year
Secondary	California Verbal Learning Test (CVLT)	Number of words remembered immediate and delayed out of a list of 16 words- (max is 16)	1 year
Secondary	Conventional MRI outcomes	Conventional MRI metrics: lesion burden: number and volume of lesions	9 months
Secondary	Timed 25-foot walk test (T25FWT)	Eval of gait, Change of 20% in the T25FWT (seconds) represents a meaningful change	1 year
Secondary	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
Secondary	Myelin water fraction (MWF)	Non-conventional MRI metrics : myelin water fraction (MWF)	9 months