Multiple SclerosisPhase 2NCT05893225
Metformin Add-on Clinical Study in Multiple Sclerosis to Evaluate Brain Remyelination And Neurodegeneration
A Phase 2 study testing Metformin Hydrochloride 850 mg Oral Tablet in people with Multiple Sclerosis and Primary Progressive Multiple Sclerosis, run by University Hospital, Antwerp at 5 sites in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Secondary-progressive Multiple Sclerosis
- What is being tested?
- Metformin Hydrochloride 850 mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 5 sitesBelgium
- Study dates
- 23 Nov 2023to 28 Feb 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- ≥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)
Who cannot join
- 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
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- Use of an experimental therapy in the past 6 months
- Ongoing immune reconstitution therapy schedule (cladribine second course ended at least 12 months before inclusion, alemtuzumab second/last course at least 12 months before inclusion, Autologous Hematopoietic Stem Cell Transplantation at least 12 months before inclusion)
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Belgium5 sites
AZ Sint-Jan Brugge
Bruges
Antwerp University Hospital
Edegem
University Hospital Ghent
Ghent
National MS Center Melsbroek
Melsbroek
Noorderhart
Overpelt
About this study
Official title: MACSiMiSE-BRAIN: Metformin add-on Clinical Study in Multiple Sclerosis to Evaluate Brain Remyelination and Neurodegeneration: a Phase II Placebo-controlled Randomized Clinical Trial
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.
Read the detailed description
Multiple Sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease leading to focal and diffuse damage of myelin sheath and axons in the central nervous system (CNS). Pathophysiologically, the adaptive and innate immune system are involved in the inflammatory process, while mitochondrial dysfunction, oxidative stress and failure of remyelination are important mechanisms leading to chronic neurodegeneration. Despite currently available disease modifying treatments (DMTs) that target the immune system, patients continue to accumulate disability. Unfortunately, no neuroprotective or remyelinating agents are available to treat progressive MS. Hence, drugs to tackle disease progression in MS represent a major unmet need. In this respect, metformin is a very interesting drug to investigate in MS patients as a neuroprotective and remyelinating therapy. Several preclinical studies in animal models of MS have shown that metformin has both anti-inflammatory, neuroprotective and remyelinating properties. A clinical study with metformin in a limited sample of MS patients did not demonstrate significant adverse events. The aim of this clinical trial is to provide evidence for the neuroprotective and remyelinating effects of metformin (I) in MS patients (P) via measurement of clinical and MRI outcome measures (O), via a multicentre randomized placebo-controlled (C) clinical trial.
- Conditions
- Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Secondary-progressive Multiple Sclerosis
- Being tested
- Metformin Hydrochloride 850 mg Oral Tablet, Placebo
- 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
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Sclerosis, Pathologic Processes, Demyelinating Autoimmune Diseases, CNS, Autoimmune Diseases of the Nervous System, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin Hydrochloride 850 mg Oral TabletDrug
Metformin Hydrochloride oral tablets 850 mg t.i.d. or b.i.d.
PlaceboDrug
Placebo matching Metformin Hydrochloride oral tablets t.i.d. or b.i.d.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Active comparator | The treatment group will receive Metformin Hydrochloride oral tablets 850mg tid or bid, during a maximum of 96 weeks. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in walking speed
Change in walking speed as measured by the Timed 25 Foot Walk (T25FW) between baseline and 96 weeks of treatment
Measured: From baseline to 96 weeks
Secondary outcomes (7)
Change in cognitive function
Change in cognitive function as measured by Symbol Digit Modalities Test (SDMT) between baseline and 96 weeks of treatment
Measured: From baseline to 96 weeks
Change in hand function
Change in hand function as measured by Nine-Hole Peg Test (9HPT) between baseline and 96 weeks of treatment
Measured: From baseline to 96 weeks
Change in EDSS
Change in Expanded Disability Status Scale. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10.0 (death) and is determined based on functional system scores (FSS) that are assigned after a standardized clinical neurological examination.
Measured: From baseline to 96 weeks
Change in brain volume
Change in brain volume (whole brain volume and gray matter volume) from baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Measured: From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Change in T2 lesion volume
Change in T2 lesion volume from baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Measured: From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Change in T1 lesion volume
Change in T1 lesion volume from baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Measured: From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Change in brain magnetic resonance imaging diffusion tensor imaging (MRI-DTI) metrics
Change in brain MRI-DTI metrics from baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Measured: From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2023
- Study start23 Nov 2023
- Primary completion28 Feb 2027 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Ghent, Hasselt University, AZ Sint-Jan AV, Noorderhart Pelt, National MS Center Melsbroek
- Responsible party
- Sponsor
- Investigators
- Barbara Willekens, MD, PhD, Principal investigator, University Hospital, Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05893225
- Sponsor's protocol ID
- MACSiMiSE-BRAIN
- Other IDs
- 2023-503190-38-00, 2023
- Status last verified
- Apr 2025
- First submitted
- 28 Feb 2022
- Last updated
- 24 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Protocol section 14.9 Access to the Study Data describes this in detail.
Publications
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.
PubMed 38680485
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MACSiMiSE-BRAIN: Metformin add-on Clinical Study in Multiple Sclerosis to Evaluate Brain Remyelination and Neurodegeneration: a Phase II Placebo-controlled Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05893225
- Acronym / sponsor ID
- MACSiMiSE-BRAIN
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- University Hospital, Ghent, Hasselt University, AZ Sint-Jan AV, Noorderhart Pelt, National MS Center Melsbroek
- Study start
- 23 Nov 2023 (actual)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 7 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Multiple Sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease leading to focal and diffuse damage of myelin sheath and axons in the central nervous system (CNS). Pathophysiologically, the adaptive and innate immune system are involved in the inflammatory process, while mitochondrial dysfunction, oxidative stress and failure of remyelination are important mechanisms leading to chronic neurodegeneration. Despite currently available disease modifying treatments (DMTs) that target the immune system, patients continue to accumulate disability. Unfortunately, no neuroprotective or remyelinating agents are available to treat progressive MS. Hence, drugs to tackle disease progression in MS represent a major unmet need. In this respect, metformin is a very interesting drug to investigate in MS patients as a neuroprotective and remyelinating therapy. Several preclinical studies in animal models of MS have shown that metformin has both anti-inflammatory, neuroprotective and remyelinating properties. A clinical study with metformin in a limited sample of MS patients did not demonstrate significant adverse events. The aim of this clinical trial is to provide evidence for the neuroprotective and remyelinating effects of metformin (I) in MS patients (P) via measurement of clinical and MRI outcome measures (O), via a multicentre randomized placebo-controlled (C) clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Active comparator | Drug: Metformin Hydrochloride 850 mg Oral TabletThe treatment group will receive Metformin Hydrochloride oral tablets 850mg tid or bid, during a maximum of 96 weeks. |
| Control group | Placebo comparator | Drug: PlaceboThe control group will receive a matching placebo, during a maximum of 96 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- A diagnosis of non-active progressive Multiple Sclerosis (PPMS and SPMS), as evidenced by:
- 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:
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin Hydrochloride 850 mg Oral TabletMetformin Hydrochloride oral tablets 850 mg t.i.d. or b.i.d. | Drug | Treatment group |
| PlaceboPlacebo matching Metformin Hydrochloride oral tablets t.i.d. or b.i.d. | Drug | Control group |
Primary outcome
Change in walking speed
Time frame: From baseline to 96 weeks
Change in walking speed as measured by the Timed 25 Foot Walk (T25FW) between baseline and 96 weeks of treatment
7 secondary outcomes
Change in cognitive function
Time frame: From baseline to 96 weeks
Change in hand function
Time frame: From baseline to 96 weeks
Change in EDSS
Time frame: From baseline to 96 weeks
Change in brain volume
Time frame: From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Change in T2 lesion volume
Time frame: From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Change in T1 lesion volume
Time frame: From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Change in brain magnetic resonance imaging diffusion tensor imaging (MRI-DTI) metrics
Time frame: From baseline to 48 weeks, from baseline to 96 weeks and from 48 to 96 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2025.
- Background: PubMed 38680485De 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.
- Individual participant dataSharing planned: Yes. Protocol section 14.9 Access to the Study Data describes this in detail.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbara Willekens, MD, PhD principal investigator
University Hospital, Antwerp
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin Hydrochloride 850 mg Oral Tablet in people with Multiple Sclerosis and Primary Progressive Multiple Sclerosis, run by University Hospital, Antwerp at 5 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in walking speed (time frame: From baseline to 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05893225, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2025.