Clemastine Fumarate for Multiple Sclerosis

(ReVIVE Trial)

Overseen By Angelica Montevirgen

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)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Clemastine Fumarate can repair nerve damage in individuals with relapsing-remitting multiple sclerosis (MS). The goal is to determine if this medication can restore the protective covering of nerves (myelin) using advanced MRI scans. Individuals with MS who have had the condition for less than 15 years and exhibit noticeable nerve damage might be suitable candidates. Participants will begin with either Clemastine or a placebo (a sugar pill) and switch after 90 days. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and to measure its effectiveness in an initial, smaller group.

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 been treated with certain medications like corticosteroids within 30 days before the trial. It's best to discuss your current medications with the trial team to see if they might affect your participation.

Is there any evidence suggesting that Clemastine Fumarate is likely to be safe for humans?

Research has shown that clemastine fumarate, a common allergy medicine, might help treat multiple sclerosis (MS) by repairing the protective layer around nerves. However, some studies have raised concerns. For instance, a recent study found that clemastine could increase disability in people with progressive MS. This suggests that while it might help repair nerve damage, it could also worsen some symptoms. These findings apply to specific types of MS, and further research is needed to fully understand clemastine's effects. Prospective trial participants should discuss these findings with their doctor. ^{1 2 3 4 5}

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

Clemastine Fumarate is unique because it offers a potential new approach for treating multiple sclerosis (MS). Unlike standard treatments like interferons or glatiramer acetate, which primarily aim to modulate the immune system, clemastine works as an antihistamine that may promote remyelination, the process of repairing damaged nerve coverings. This new mechanism of action could help restore nerve function rather than just slowing disease progression. Researchers are excited about this potential to not only halt the disease but also reverse some of the damage it causes, offering hope for improved outcomes for people living with MS.

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

Research has shown that clemastine fumarate might help repair nerve damage in people with multiple sclerosis (MS). In a previous study, this medication improved nerve function by reducing the time it takes for signals to travel through nerves by 1.7 milliseconds per eye. The study focused on optic neuropathy, a condition linked to MS. Although clemastine fumarate is usually used as an antihistamine, it also blocks certain receptors, which might help repair the myelin, the protective layer around nerves. In the current trial, participants will receive clemastine fumarate or a placebo in a crossover design, allowing researchers to assess its effects on MS. While clemastine fumarate seems promising for some types of MS, other trials have noted increased disability in different forms, indicating that its effects can vary. ^{1 2 4 6 7}

Who Is on the Research Team?

Ari J Green, MD, MCR

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 (MS) diagnosed within the last 15 years. Participants must use effective birth control and provide informed consent. Excluded are those with recent MS lesions, hypersensitivity to clemastine, steroid treatment within 30 days, cancer history, suicidal behavior in past 6 months, pregnancy or breastfeeding intentions, other concurrent study involvement without approval.

Inclusion Criteria

- Not heterosexually active (patients who are not heterosexually active at screening must agree to utilize a highly effective method of birth control if they become heterosexually active during their participation in the study)

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

I have been post-menopausal for at least one year.

Exclusion Criteria

I have a history of serious heart rhythm problems.

You have had issues with drugs or alcohol in the past year.

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, followed by a switch to the alternate treatment for another 90 days

6 months

Baseline, 3-month, and 6-month visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Clemastine Fumarate

Trial Overview The trial tests Clemastine Fumarate as a potential myelin repair therapy against a placebo in MS patients. It measures changes using multi-parametric MRI and a new technique called Ultrashort Echo Time (UTE) MRI to assess remyelination of chronic brain lesions.

How Is the Trial Designed?

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

Group 2 will receive the placebo (a sugar pill) for the first 90 days and then switch to the treatment (clemastine 8mg/day) for the remaining 90 days

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

Group 1 will receive the treatment (clemastine 8mg/day) for the first 90 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+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

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]

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]

Dimethyl-fumarate, an approved treatment for relapsing-remitting Multiple Sclerosis, was well-tolerated by a 55-year-old woman, with the only notable side effect being moderate flushing.

Although transient hair loss was not previously reported as a side effect of dimethyl-fumarate, it was observed in this patient after starting the therapy, but it resolved after two months, suggesting a possible link to the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient hair loss during treatment with dimethyl-fumarate for multiple sclerosis. Losavio, FA., Lucchini, M., De Fino, C., et al.[2017]

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]

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. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673617323462

Articles Clemastine fumarate as a remyelinating therapy for ... The primary efficacy endpoint was met with clemastine fumarate treatment, which reduced the latency delay by 1·7 ms/eye (95% CI 0·5–2·9; p=0·0048) when ...

4. 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.

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

Clemastine Fumarate Drives Disease Progression in ... Clemastine fumarate amplifies disease progression in progressive MS by amplifying innate immune responses.

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 ... Clemastine fumarate, an over-the-counter (OTC) antihistamine thought to have remyelinating potential in MS, may actually accelerate disability accumulation.

7. mdedge.com mdedge.com/neurologyreviews/article/268320/multiple-sclerosis/unexpected-finding-clemastine-fumarate-linked

In Unexpected Finding, Clemastine Fumarate Linked to ... An over-the-counter antihistamine that had shown potential for treatment of multiple sclerosis (MS) in animal studies was linked to significant worsening of ...