The late breaker we have all been waiting for metformin and clemastin. It was presented a short while ago and it was positive in that the primary endpoint was met and there was improvement and.it was statistically positive…So this is great news. But the effect was not great.
There was an increase in the optic nerve transmission but there was no detectable clinical benefit. Some of the other markers failed to change significantly. This should not be a downer as they have not been truly validated. Whole brain atrophy was questionable in the O hand trial. It is a start and perhaps people with earlier disease are more likely to respond but it warms that the effects are not transformative and the best way is to stop disease and stop the damage in the first place
Abstract Number: 152/O133 Evaluating the remyelinating efficacy and safety of the combination of metformin and clemastine in people Evaluating the remyelinating efficacy and safety of the combination of metformin and clemastine in people with relapsing remitting multiple sclerosis with relapsing remitting multiple sclerosis (CCMR-Two CCMR-Two): a randomised, placebo-controlled, double-blind, : a randomised, placebo-controlled, double-blind, phase 2 clinical trial. phase
Nick G. Cunniffe et al.
Introduction: Preclinical research has shown that metformin can promote remyelination by reversing an age-associated deficit in the responsiveness of oligodendrocyte progenitor cells (OPCs) to pro-differentiation factors. Clemastine, a repurposed anti-histamine, has previously been shown to promote OPC differentiation and led to improvements in visual evoked potential (VEP) latency in a phase 2 trial.
Objectives/Aims: The purpose of the Cambridge Centre for Myelin Repair trial Two (CCMR-Two) is to evaluate the efficacy of the combination of metformin and clemastine to promote remyelination in people with MS. Methods: Methods: CCMR-Two is a single-centre, randomised, placebo-controlled, double-blind phase 2 trial conducted in Cambridge, UK. Key eligibility criteria were: relapsing remitting MS (RRMS), stable on a disease modifying treatment for at least 6 months, age 25-50 years, Expanded Disability Status Scale (EDSS) score ≤ 6.0, and evidence of chronic stable optic neuropathy in at least one eye (defined by P100 latency of the full-field pattern-reversal VEP ≥118 ms, and the absence of a history of acute optic neuritis in the preceding two years). Participants are allocated to the combination of metformin 1g and clemastine 5.36mg twice daily or matched placebos in a 1:1 ratio for 6 months of treatment. The primary outcome measure is the change in the P100 latency of the full-field VEP between baseline and week 26. Secondary endpoints include safety, change in multi-focal VEP and change in the magnetization transfer ratio (MTR) characteristics of MS lesions.Trial registration: Trial registration: NCT05131828. CCMR-Two was funded by the UK MS Society
Results: Between March 2022 and September 2024, 178 participants were screened with 70 participants randomised. The baseline characteristics (mean (standard deviation)) were: age 41.6 years (5.4), duration of MS 12.9 years (6.9), EDSS 2.6 (1.4) and 70% were female. Three participants discontinued the investigational medicinal product (2 withdrew consent, 1 experienced disabling sedation). The remaining 67 participants completed 6 months of treatment.
Conclusion: Conclusion: Top-line results of primary and major secondary outcomes, as well as safety data, will be reported in this session.
Source: multiple-sclerosis-research.org