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Metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration: a phase IIb triple-blind placebo-controlled randomized clinical trial (MACSiMiSE-BRAIN)
EU CTIS ID: 2023-503190-38-00
What this study is testing
The primary objective is to determine if treatment with metformin is able to delay disease progression in comparison to placebo in patients with non-active progressive multiple sclerosis. It is hypothesized that metformin, as add-on treatment, in patients with PMS is superior to placebo in slowing disease progression. This will be measured by the primary outcome that is change in walking speed as measured by the T25FW between baseline and 96 weeks of treatment, between the control (placebo) and intervention (metformin) group.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- A diagnosis of non-active progressive multiple sclerosis (including PPMS and SPMS, in accordance with 2017 revisions of McDonald criteria and disease course definitions of Lublin 2013), as evidenced by: a. the absence of relapses and new T2 lesions and/or enhancing T1 lesions on brain MRI in the past 1-2 years or longer (NEDA-2) b. 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 T25W • ≥20% 9HPT (on average of both hands and/or the dominant hand and/or the non-dominant hand) • 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 TSC, 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 and French speaking (patient reported outcomes and questionnaires available in Dutch/Flemish and French)
- Stable use of DMT or no treatment in the past year or longer
You likely can't join if
- A medical or neurological problem other than MS that is a cause of progressive or fluctuating gait dysfunction
- Current use of metformin or known intolerance for metformin
- 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 <60 mL/min/1.73 m2, end-stage cardiopulmonary disease, alcoholism, liver insufficiency with AST >3 times ULN, chronic active infection etc.) that may interfere with study procedures and/or intake of study drug.
See the full eligibility criteria
- A diagnosis of non-active progressive multiple sclerosis (including PPMS and SPMS, in accordance with 2017 revisions of McDonald criteria and disease course definitions of Lublin 2013), as evidenced by: a. the absence of relapses and new T2 lesions and/or enhancing T1 lesions on brain MRI in the past 1-2 years or longer (NEDA-2) b. 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 T25W • ≥20% 9HPT (on average of both hands and/or the dominant hand and/or the non-dominant hand) • 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 TSC, 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 and French speaking (patient reported outcomes and questionnaires available in Dutch/Flemish and French)
- Stable use of DMT or no treatment in the past year or longer
- Use of adequate contraceptive measures in females of reproductive age
- A medical or neurological problem other than MS that is a cause of progressive or fluctuating gait dysfunction
- Current use of metformin or known intolerance for metformin
- 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 <60 mL/min/1.73 m2, end-stage cardiopulmonary disease, alcoholism, liver insufficiency with AST >3 times 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
- 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, AHSCT at least 12 months before inclusion)
- Expected change in ongoing DMT or start of DMT if untreated
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.