NCT05131828

CCMR Two: A Phase IIa, Randomised, Double-blind, Placebo-controlled Trial of the Ability of the Combination of Metformin and Clemastine to Promote Remyelination in People With Relapsing-remitting Multiple Sclerosis Already on Disease-modifying Therapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: Cambridge University Hospitals NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 25 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

The greatest unmet need for people with multiple sclerosis is an effective therapy for the progressive phase. Current treatments suppress the damage caused by the immune system but there is only a limited window in which these can work. Consequently, much of the research community is turning its attention to the process of repair, called remyelination, in which the lining of nerve cells is reformed. This protects nerves from dying and therefore can delay, prevent, or even reverse, disability progression. It has previously been shown that stem cells are already present in the brain that can carry out this process. Clemastine, an anti-histamine drug, can instruct them to become active and has already shown a beneficial effect in a phase 2 trial. Now, more recent experiments have shown that changes take place within these stem cells as they age, which prevents them responding to drugs like clemastine, but that this can be reversed by treatment with metformin, a commonly used anti-diabetes drug. Our goal is to establish whether the combination of metformin and clemastine can promote remyelination in people with MS. We will focus on people with relapsing MS as they will have a greater proportion of nerves healthy enough to allow remyelination to take place, which will maximise the chance of detecting an effect with a smaller sample size. Participants will also continue treatment with a current disease-modifying MS treatment, to reduce the chance of developing new areas of damage, allowing the trial to focus on the repair process. The treatment duration will be 24 weeks, but given the established safety of the proposed medications, we are able to limit the number of visits to the trial centre to ensure participation is not overly burdensome.

Conditions

• Multiple Sclerosis

Interventions

Type	Name	Description
DRUG	Metformin and clemastine in combination	Metformin hydrochloride 500 mg prolonged release (SR) tablet for oral administration. Clemastine hydrogen fumarate 1.34 mg tablet for oral administration.
DRUG	Placebo	Placebo tablets to match both metformin and clemastine tablets.

Timeline

• Start date: 2022-03-08
• Primary completion: 2025-03-31
• Completion: 2025-09-26
• First posted: 2021-11-23
• Last updated: 2025-12-11

Locations

1 site across 1 country: United Kingdom