Metformin Treatment in Progressive Multiple Sclerosis

A Double-blind, Placebo Controlled Trial of Metformin Treatment in Progressive Multiple Sclerosis

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

Study Overview

• Status: Recruiting
• Conditions: Primary Progressive Multiple Sclerosis; Secondary Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: Metformin 500 Mg Oral Tablet, up to 4 tablets a day; Drug: Placebo oral tablet identical to metformin, up to 4 tablets a day

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.

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Kevin R Patel, MD; Phone Number: 310 205 2176; Email: KevinPatel@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles
      • Contact: Michael Montag; Phone Number: 310-205-2176; Email: mmontag@mednet.ucla.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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
Placebo Comparator: 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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with adverse events between baseline and conclusion (month 0 and month 12)	number of patients with adverse events comparing the two treatment groups	between month 0 and month 12
number of patients with laboratory abnormalities between baseline and conclusion (month 0 and month 12)	number of patients with laboratory abnormalities comparing the two treatment groups	between month 0 and month 12
number of patients with new T2 lesions on MRI from baseline to conclusion (month 0 and month 12)	number of patients with new T2 lesions comparing the two treatment groups	between month 0 and month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
a reduction in localized cortical thinning on brain MRI between baseline and conclusion (month 0 and month 12)	a reduction in localized cortical thinning on brain MRI comparing the two treatment groups	between month 0 and month 12
a reduction in thalamic atrophy on brain MRI between baseline and conclusion (month 0 and month 12)	a reduction in thalamic atrophy on brain MRI comparing the two treatment groups	between month 0 and month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
improvement in SDMT-oral score between baseline and conclusion (month 0 and month 12)	improvement in SDMT-oral score between comparing the two treatment groups	between month 0 and month 12
improvement in CVLT-II score between baseline and conclusion (month 0 and month 12)	improvement in CVLT-II score between comparing the two treatment groups	between month 0 and month 12
improvement in PACC score between baseline and conclusion (month 0 and month 12)	improvement in PACC score between comparing the two treatment groups	between month 0 and month 12
improvement in PASAT score between baseline and conclusion (month 0 and month 12)	improvement in PASAT score between comparing the two treatment groups	between month 0 and month 12
decrease in plasma neurofilament light chain levels between baseline and conclusion (month 0 and month 12)	decrease in plasma neurofilament light chain levels comparing the two treatment groups	between month 0 and month 12
decrease in number of phase rimmed lesions between baseline and conclusion (month 0 and month 12)	decrease in number of phase rimmed lesions comparing the two treatment groups	between month 0 and month 12

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Kevin R Patel, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2022
• Primary Completion (Anticipated): May 26, 2025
• Study Completion (Anticipated): May 26, 2026

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 27, 2022

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 3, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Demyelinating disease
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 22-000020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No