Metformin Add-on Clinical Study in Multiple Sclerosis to Evaluate Brain Remyelination And Neurodegeneration

NCT05893225 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: MACSiMiSE-BRAIN2023-503190-38-00
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 5

Brief Summary

This clinical trial aims to demonstrate that metformin can prevent clinical disability in patients with progressive MS by stopping or slowing down neurodegeneration by enhancing endogenous remyelination. Patients will continue their DMT treatment: metformin or placebo will be used as add-on study treatment.

Conditions

Multiple Sclerosis; Primary Progressive Multiple Sclerosis; Secondary-progressive Multiple Sclerosis

Keywords

Multiple Sclerosis; Primary Progressive Multiple Sclerosis; Secondary Progressive Multiple Sclerosis; Sclerosis; Metformin; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Brain Remyelination; Neurodegeneration

Outcome Measures

Primary Outcomes (1)

• Change in walking speed

  Change in walking speed as measured by the Timed 25 Foot Walk (T25FW) between baseline and 96 weeks of treatment

  From baseline to 96 weeks

Secondary Outcomes (7)

• Change in cognitive function

  From baseline to 96 weeks

• Change in hand function

  From baseline to 96 weeks

• Change in EDSS

  From baseline to 96 weeks

• Change in brain volume

  From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks

• Change in T2 lesion volume

  From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks

Other Outcomes (7)

• Change in quality of life measured by EQ-5D-5L

  From baseline to 96 weeks

• Change in quality of life measured by MSIS-29

  From baseline to 96 weeks

• Change in the Composite endpoint

  From baseline to 96 weeks

Study Arms (2)

Treatment group

ACTIVE COMPARATOR

The treatment group will receive Metformin Hydrochloride oral tablets 850mg tid or bid, during a maximum of 96 weeks.

Drug: Metformin Hydrochloride 850 mg Oral Tablet

Control group

PLACEBO COMPARATOR

The control group will receive a matching placebo, during a maximum of 96 weeks.

Drug: Placebo

Interventions

Metformin Hydrochloride 850 mg Oral Tablet DRUG

Metformin Hydrochloride oral tablets 850 mg t.i.d. or b.i.d.

Treatment group

Placebo DRUG

Placebo matching Metformin Hydrochloride oral tablets t.i.d. or b.i.d.

Control group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of non-active progressive Multiple Sclerosis (PPMS and SPMS), as evidenced by:
• the absence of relapses and new T2 lesions on brain MRI in the past year or longer (No Evidence of Disease Activity-2)
• progression of disability independent of relapses in the past 1-2 years or longer
• If progression is defined as one of the following, over the past 1-2 years or less, the patient can be included without additional review:
• minimum increase in the EDSS of 1.0, or 0.5 from a baseline level of 2.0-5.0, and 5.5-6.0, respectively
• ≥20% in the T25FW
• ≥20% 9HPT
• reduction of ≥4 points or a 10% worsening in the Symbol Digit Modality Test without concomitant depression or fatigue.
• If the investigator is in the opinion that the patient is clearly progressing, but not enough data are available to demonstrate this, a narrative needs to be provided, which will be judged by at least 2 members of the Trial Steering Committee, from a center that is not submitting the case for review.
• Age 18-70 years inclusive
• EDSS 2.0-6.5 inclusive
• Able to give informed consent (signed, written) and to adhere to study procedures
• Dutch/Flemish speaking (patient reported outcomes and questionnaires available in Dutch/Flemish)
• Stable use of Disease Modifying Treatment (DMT) or no treatment in the past year or longer
• Use of adequate contraceptive measures in women of childbearing potential (WOCBP)

You may not qualify if:

• A medical or neurological problem other than MS that is a cause of progressive or fluctuating gait dysfunction
• Diagnosis of diabetes mellitus or fasting glucose level of 126mg/dl or more; random glucose level of 200mg/dl or more; HbA1C of 6.5% or more at screening
• Unable to complete T25FW
• Unable to undergo MRI
• Current major disease or disorder other than MS (e.g., active malignancy, significant renal insufficiency eGFR (estimated Glomerular Filtration Rate) \<60 mL/min/1.73 m2, end-stage cardiopulmonary disease, alcoholism, liver insufficiency with AST (aspartate aminotransferase) \>3 times Upper Limit of Normal (ULN), chronic active infection etc.) that may interfere with study procedures and/or intake of study drug
• Pregnant or breast-feeding or planning pregnancy
• Use of an experimental therapy in the past 6 months
• Expected change in ongoing DMT or start of DMT if untreated
• Current use of metformin or known intolerance for metformin
• Known sensitivity to the active substance or to any of the excipients listed in section 6.1 of the Summary of Product Characteristics.
• All forms of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis), diabetic precoma.
• Acute conditions where there is a risk of alteration of renal function, such as: dehydration, severe infection, shock occurring between screening and randomization.
• Chronic use of NSAID

Sponsors & Collaborators

• University Hospital, Antwerp: lead
• University Hospital, Ghent: collaborator
• Hasselt University: collaborator
• AZ Sint-Jan AV: collaborator
• Noorderhart Pelt: collaborator
• National MS Center Melsbroek: collaborator

Study Sites (5)

AZ Sint-Jan Brugge

Bruges, Belgium

Location

Antwerp University Hospital

Edegem, Belgium

Location

University Hospital Ghent

Ghent, Belgium

Location

National MS Center Melsbroek

Melsbroek, Belgium

Location

Noorderhart

Overpelt, Belgium

Location

Related Publications (1)

• De Keersmaecker AV, Van Doninck E, Popescu V, Willem L, Cambron M, Laureys G, D' Haeseleer M, Bjerke M, Roelant E, Lemmerling M, D'hooghe MB, Derdelinckx J, Reynders T, Willekens B. A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial. Front Immunol. 2024 Feb 21;15:1362629. doi: 10.3389/fimmu.2024.1362629. eCollection 2024.

  PMID: 38680485 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nerve Degeneration

Interventions

Metformin; Tablets

Condition Hierarchy (Ancestors)

Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathological Conditions, Signs and Symptoms; Leukoencephalopathies; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Barbara Willekens, MD, PhD

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2022
• First Posted: June 7, 2023
• Study Start: November 23, 2023
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: June 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After peer-reviewed publication of study protocol and clinical trial results
• Access Criteria: See protocol section 14.9 Access to the Study Data

Locations

BE (5)