Metformin Treatment in Progressive Multiple Sclerosis

NCT ID: NCT05349474

Last Updated: 2025-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-26
• Study Completion Date: 2025-05-30

Brief Summary

The purpose of this study is to assess the safety of metformin for treatment of progressive multiple sclerosis

Detailed Description

This will be a single site 1:1 randomized, placebo controlled trial of metformin treatment vs matching placebo in 44 men and women with primary progressive multiple sclerosis and secondary multiple sclerosis, without diabetes, not treated with metformin aged 30-65. The trial will last 12 months and have 3 study visits, baseline, 6 months, and 12 months. The trial will be preceded by a screening period. Over the initial 30 day titration period subjects will be titrated from 500 mg a day to 2,000 mg of metformin in increments of 500 mg every 10 days. Patients will remain on their tolerated dose and included in analysis on an intent to treat basis. Brain MRI, cognitive testing and clinical measures will be collected at baseline, month 6 and month 12. OCT will be collected at baseline and month 12. The primary outcomes are the following safety outcomes: 1) number of patients with adverse events 2) number of patients with laboratory abnormalities 3) number of patients with new T2 lesions on MRI. The secondary outcomes include reduction in localized cortical thinning on brain MRI; reduction in thalamic atrophy on brain MRI. Further exploratory outcomes include 1) improvement in SDMT-oral score, 2) improvement in CVLT-II score, 3) improvement in PACC score 4) improvement in PASAT score. Exploratory outcomes include 1) Decrease in plasma neurofilament light chain levels, 2) Reginal nerve fiber layer preservation on OCT, 3) Ganglion cell inner plexiform layer preservation, and 4) Percentage of phase rim lesions.

Conditions

Secondary Progressive Multiple Sclerosis; Primary Progressive Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo Treatment

Placebo tablets identical to metformin 500 mg tablets divided into two doses. Patients will be started on 1 tablet a day and a titration to maximum dose (4 tablets) will be attempted during the first 30 day period of the study.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet identical to metformin, up to 4 tablets a day

Intervention Type: DRUG

Placebo tablets identical to metformin tablets. To be titrated to four tablets divded over two doses or maximum tolerated dose

Metformin Treatment

Metformin 500 mg tablets up to 2,000 mg (4 tablets) a day divided into two doses. Patients will start on 500 mg Qday and a titration to maximum dose will be attempted during the first 30 day period of the study.

Group Type: EXPERIMENTAL

Metformin 500 Mg Oral Tablet, up to 4 tablets a day

Intervention Type: DRUG

Metformin 500 mg oral tablets to be titrated to 2000 mg/day divided over two doses or maximum tolerated dose

Interventions

Metformin 500 Mg Oral Tablet, up to 4 tablets a day

Metformin 500 mg oral tablets to be titrated to 2000 mg/day divided over two doses or maximum tolerated dose

Intervention Type: DRUG

Placebo oral tablet identical to metformin, up to 4 tablets a day

Placebo tablets identical to metformin tablets. To be titrated to four tablets divded over two doses or maximum tolerated dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient signed informed consent.

2. Age 30-65

3. Primary Progressive Multiple Sclerosis or Secondary Progressive Multiple Sclerosis as defined by the 2017 McDonald Criteria

4. Intent to maintain current MS disease modifying treatment through the trial duration

Exclusion Criteria

1. Clinical relapse in prior 12 months

2. New T2 lesion or gadolinium enhancing lesion in prior 12 months

3. Glucocorticoid use in prior six months outside the context of premedication for disease modifying treatment

4. Changes in disease modifying therapy in prior three months

5. Plans to change current disease modifying therapy

6. Contraindication to MRI, inability to tolerate MRI

7. Use of metformin for any other indication

8. Renal dysfunction (GFR < 60)

9. Hepatic dysfunction (AST or ALT > 1.5 x upper limit of normal)

10. B12 deficiency

11. Prior poor reaction to metformin

12. Congestive heart failure

13. Alcohol abuse

14. Metabolic acidosis

15. Females who are pregnant or who plan to become pregnant during the 12 months of enrollment, or who wish to breastfeed during any part of the 12 months of enrollment

16. Concomitant use of drugs with drug-drug interactions with metformin

17. Previous adverse effect with metformin treatment

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Kevin Patel

Assistant Professor, Department of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kevin R Patel, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

University of California, Los Angeles

Los Angeles, California, United States

Countries

United States

Other Identifiers

22-000020

Identifier Type: -

Identifier Source: org_study_id