Myelin Repair Therapy for Multiple Sclerosis

(ReINFORCE Trial)

Overseen By Ari J Green, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Francisco

Must not be taking: Corticosteroids, Alemtuzumab, Mitoxantrone, others

Disqualifiers: Brain atrophy, Cardiac block, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a potential new treatment, clemastine fumarate (an antihistamine), to determine if it can repair damaged myelin, the protective covering of nerves, in people with multiple sclerosis (MS). Researchers aim to discover if it can fix brain damage caused by MS. The trial compares clemastine fumarate to a placebo (a sugar pill with no active medicine) to evaluate effectiveness. People with relapsing-remitting MS who have had the disease for less than 15 years might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this potential new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use any other remyelinating therapy or have had certain treatments like alemtuzumab, mitoxantrone, or cyclophosphamide. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research suggests that clemastine fumarate, a common allergy medicine, might help repair nerve damage in people with multiple sclerosis (MS). However, safety remains a concern. Some studies have found that clemastine could accelerate disability progression in certain types of MS. For example, one study showed that some patients' conditions worsened more quickly after taking clemastine.

In another study, researchers stopped the clemastine treatment because it was linked to increased disability in patients with a type of MS not associated with new brain lesions. While clemastine shows promise for nerve repair, these safety issues require careful consideration. Always consult a healthcare provider about the risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple sclerosis?

Researchers are excited about clemastine fumarate for multiple sclerosis (MS) because it represents a fresh approach to treating the disease. Unlike many current MS treatments that focus on modulating the immune system, clemastine is believed to promote myelin repair. Myelin is the protective sheath around nerve fibers that gets damaged in MS, leading to symptoms. Clemastine’s potential to repair myelin could mean addressing the root of the damage rather than just managing symptoms. This could be a game-changer for patients, offering hope for not just slowing progression but possibly restoring function.

What evidence suggests that Clemastine Fumarate might be an effective treatment for multiple sclerosis?

Research shows that clemastine fumarate, a common allergy medicine, might help repair damage in multiple sclerosis (MS) by encouraging the regrowth of myelin, the protective layer around nerves. An earlier study found that clemastine improved the speed of nerve signals in people with MS-related vision problems, suggesting the drug might help restore myelin, which gets damaged in MS. The study also indicated a possible improvement in vision, highlighting its potential benefits. This trial will evaluate clemastine fumarate as a promising option for myelin repair, with participants receiving either clemastine followed by a placebo or a placebo followed by clemastine. Since current treatments don't repair myelin, clemastine fumarate offers a promising new option. ^{1 2 6 7 8}

Who Is on the Research Team?

Ari J Green, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with relapsing-remitting multiple sclerosis and disease duration under 15 years. Participants must use effective birth control, not be pregnant or breastfeeding, and have no severe medical issues or recent drug/alcohol abuse. They can't have certain treatments like corticosteroids within the last month or a new lesion on their latest MRI.

Inclusion Criteria

Written informed consent must be obtained prior to any assessment being performed

I have relapsing-remitting MS diagnosed within the last 15 years.

I am a woman not at risk of becoming pregnant due to menopause, surgery, effective birth control, or not having heterosexual sex.

Exclusion Criteria

Pregnancy, breastfeeding or planning to become pregnant

Any dental braces or permanent or undetachable metals in the jaw or face

I have not taken corticosteroids in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Clemastine Fumarate or placebo for 90 days, with dosage adjustments during the period

12 weeks

Regular visits for monitoring and MRI assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, with MRI assessments at 3 and 6 months

6 months

Visits at 3-month and 6-month intervals

What Are the Treatments Tested in This Trial?

Interventions

• Clemastine Fumarate
• Placebo

Trial Overview The study tests Clemastine Fumarate as a potential myelin repair therapy against a placebo in patients with acute demyelinating brain lesions using advanced MRI techniques to measure its effects.

How Is the Trial Designed?

Group I: Placebo, then Clemastine 12 mg, then Clemastine 8 mg Experimental Treatment 2 Interventions

Group 1 will receive the placebo for the first 90 days. Then, they will switch to clemastine (treatment) for 90 days. They will receive clemastine 12 mg for 14 days followed by clemastine 8 mg for the remaining 76 days.

Group II: Clemastine 12 mg, then clemastine 8 mg, then Placebo Experimental Treatment 2 Interventions

Group 1 will receive the treatment (clemastine) for the first 90 days. They will receive clemastine 12 mg for 14 days followed by clemastine 8 mg for 76 days, and then switch to the placebo (a sugar pill) for the remaining 90 days

Clemastine Fumarate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Clemastine for:

• Allergic rhinitis
• Urticaria
• Pruritus

Approved in European Union as Clemastine for:

• Allergic rhinitis
• Urticaria
• Pruritus

Approved in Canada as Clemastine for:

• Allergic rhinitis
• Urticaria
• Pruritus

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a study of 735 patients with relapsing-remitting multiple sclerosis, dimethyl-fumarate (DMF) reduced the annual relapse rate by 63.2%, with 85% of patients relapse-free at 12 months.

DMF was found to be safe, with the most common side effects being flushing (37.2%) and gastro-enteric issues (31.1%), and it showed significant benefits for both treatment-naïve patients and those switching from other therapies due to tolerability or efficacy concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study. Mallucci, G., Annovazzi, P., Miante, S., et al.[2018]

In a study of 2113 patients with relapsing-remitting multiple sclerosis (RRMS), dimethyl fumarate and fingolimod were found to have similar effectiveness in reducing relapse rates and preventing disability worsening, with no significant differences in outcomes.

Both treatments showed comparable results for both treatment-naïve patients and those switching from other disease-modifying therapies, indicating that either medication can be a viable first-line option for managing RRMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of dimethyl fumarate and fingolimod in relapsing-remitting multiple sclerosis. Lorscheider, J., Benkert, P., Lienert, C., et al.[2021]

Dimethyl fumarate has been shown to significantly reduce relapse rates in patients with relapsing-remitting multiple sclerosis (MS), with a reduction of 34% to 49% in the proportion of patients experiencing relapses over two years, based on two phase III trials (DEFINE and CONFIRM).

The safety profile of dimethyl fumarate is comparable to placebo, with serious adverse effects occurring at similar rates; however, some patients experienced intolerable flushing and gastrointestinal issues, leading to discontinuation in 3% and 4% of cases, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis. Venci, JV., Gandhi, MA.[2015]

In a study of patients with multiple sclerosis, dimethyl fumarate (DMF) treatment led to a significant decrease in CD4(+) and CD8(+) memory T cells, suggesting a targeted effect on these immune cells.

DMF treatment also resulted in a shift in T helper cell populations, increasing anti-inflammatory TH2 cells while decreasing pro-inflammatory TH1 cells, which may benefit patients with TH1-driven disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate treatment alters circulating T helper cell subsets in multiple sclerosis. Gross, CC., Schulte-Mecklenbeck, A., Klinsing, S., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40371642/

Clemastine fumarate accelerates accumulation of disability in ... Clemastine fumarate, the over-the-counter antihistamine and muscarinic receptor blocker, has remyelinating potential in MS.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02040298

NCT02040298 | Assessment of Clemastine Fumarate as a ... The main purpose of this study is to assess clemastine as a remyelinating agent in patients with relapsing forms of multiple sclerosis.

3. cam.ac.uk cam.ac.uk/research/news/common-diabetes-drug-and-antihistamine-could-together-repair-multiple-sclerosis-damage-trial-finds

Diabetes drug and antihistamine could together repair ... Diabetes drug and antihistamine could together repair multiple sclerosis damage, trial finds. Dr Nick Cunniffe running a 'visual evoked ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05338450

NCT05338450 | Clemastine Fumarate as Remyelinating ... Objective: To assess the (long-term) efficacy of clemastine fumarate in improving dysconjugacy of eye movements in patients with internuclear ophthalmoparesis ...

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05359653

Assessing Changes in Multi-parametric MRI in MS Patients ... This clinical trial is intended to assess magnetic resonance imaging evidence of remyelination using Clemastine Fumarate in patients with chronic demyelinated ...

6. practicalneurology.com practicalneurology.com/news/otc-antihistamine-clemastine-may-accelerate-disability-in-those-with-progressive-ms/2470414/

OTC Antihistamine Clemastine May Accelerate Disability in ... In terms of results, 3 patients increased disability 5-times faster compared to their 18-months “baseline” progression slopes. This outcome ...

7. neurologylive.com neurologylive.com/view/clemastine-arm-trap-ms-trial-halted-following-increased-disability-accumulation-progressive-ms

Clemastine Arm of TRAP-MS Trial Halted Following ... New data from the TRAP-MS trial showed clemastine fumarate's association with increased disability accumulation in cases of non-lesional multiple sclerosis.

8. rarediseaseadvisor.com rarediseaseadvisor.com/news/clemastine-fumarate-drives-disease-progression-progressive-ms/

Clemastine Fumarate Drives Disease Progression in ... Overall, 6 of 9 patients with MS in the CLM arm experienced faster disability progression compared to their baseline rates, whereas most ...