Clemastine for Optic Neuritis

(ReCOVER Trial)

Overseen By Harkeerat Halait

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Remyelinating therapies

Disqualifiers: Diabetes, Cancer, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 10

Duration: 3 months

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests clemastine, a drug typically used for allergies, to determine if it can repair optic nerve damage in individuals with optic neuritis, a condition that causes blurry vision due to nerve damage. The study will assess whether clemastine aids nerve healing and its safety for those with this condition. Participants will receive either clemastine or a placebo for three months, followed by monitoring for an additional six months. Suitable candidates for this trial include those diagnosed with optic neuritis in one eye within the last three weeks and without other major eye issues like glaucoma or severe nearsightedness. As a Phase 2 trial, this research focuses on evaluating clemastine's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You can continue taking your standard disease-modifying treatment during the study. However, you cannot use any other remyelinating therapy or participate in another investigational drug study at the same time.

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

Research has shown that clemastine fumarate, originally used to treat allergies, is being studied for a new use: repairing nerves in optic neuritis, a condition affecting the eye nerve. In a study with 25 patients, taking clemastine for 90 days led to noticeable improvements in vision, suggesting a positive effect on the eye.

Regarding safety, studies have found that clemastine is generally well-tolerated. Since the FDA has already approved clemastine for other uses, such as treating allergies, doctors are familiar with typical patient responses. However, its use for optic neuritis remains under investigation.

Overall, past studies have not reported major safety concerns, which reassures those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for optic neuritis?

Clemastine Fumarate is unique because it offers a new approach for treating optic neuritis by potentially promoting myelin repair. Unlike standard treatments that mainly focus on reducing inflammation, such as corticosteroids, Clemastine works by enhancing the regeneration of the protective sheath around nerves, which could improve vision recovery. Researchers are excited about this treatment because it targets the underlying issue of nerve damage rather than just alleviating symptoms, potentially leading to more effective and lasting outcomes for patients.

What evidence suggests that clemastine might be an effective treatment for optic neuritis?

Studies have shown that clemastine fumarate can help treat optic neuritis, a condition affecting the eyes. In a study with 25 patients, those who took clemastine for 90 days experienced significant improvements in their vision. In this trial, some participants will receive clemastine, while others will receive a placebo. Research also suggests that clemastine protects important parts of the eye, such as the retinal nerve fiber layer and ganglion cell layer, often damaged by optic neuritis. This indicates that clemastine might help protect the eyes and improve vision. ^{1 2 5 6 7}

Who Is on the Research Team?

Ari Green, MD, MCR

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for individuals recently diagnosed or suspected to have acute optic neuritis in one eye, who understand and consent to the study. They can be on standard disease-modifying treatments but must use contraception if applicable. Exclusions include major eye diseases, significant health conditions like heart block or cancer, pregnancy, other concurrent studies without approval, and certain lab abnormalities.

Inclusion Criteria

Understand and sign the informed consent

I have or might have optic neuritis in one eye, diagnosed within the last 3 weeks.

Use of appropriate contraception during the period of trial (women)

Exclusion Criteria

I have inflammation in both of my optic nerves at the same time.

Involved with other study protocols simultaneously without prior approval

History of drug or alcohol abuse within the past year

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive clemastine or placebo for 3 months to assess remyelination and tolerability

3 months

Baseline, 1 week, 1 month, 3 months

Off-treatment Observation

Participants are observed off treatment to assess long-term effects and recovery

6 months

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Clemastine Fumarate

Trial Overview The ReCOVER trial is testing clemastine fumarate's ability to repair nerve insulation (remyelination) in patients with acute optic neuritis versus a placebo. The study will monitor remyelination through visual tests and MRI while allowing participants to continue their usual disease-modifying therapies.

How Is the Trial Designed?

Group I: Clemastine Experimental Treatment 1 Intervention

Participants will receive clemastine until 3 months and then will be off treatment until 9 month time point.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo until 3 months and then will be off treatment until 9 month time point.

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+

Moorfields Eye Hospital NHS Foundation Trust

Collaborator

Trials

72

Recruited

290,000+

Published Research Related to This Trial

Clemastine fumarate significantly reduced latency delay in visual-evoked potentials by 1.7 ms per eye in patients with relapsing multiple sclerosis, indicating its efficacy in promoting myelin repair after chronic damage.

The study, which involved 50 patients over 150 days, reported that while clemastine fumarate was associated with fatigue, it did not lead to any serious adverse events, suggesting it is a safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Green, AJ., Gelfand, JM., Cree, BA., et al.[2022]

In a study of 188 patients with anti-aquaporin-4 seropositive optic neuritis, visual acuity improved from a median of 1.30 to 0.70 logMAR over time, indicating some recovery despite the condition's resistance to steroid pulse therapy.

Additional treatments like plasma exchange and immunoadsorption did not show a significant benefit in visual acuity compared to standard care, highlighting the need for further research to evaluate their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[National clinical investigation of anti-aquaporin-4 seropositive optic neuritis]. Endo, T., Fujikado, T., Morimoto, T., et al.[2015]

Optic neuritis is a key symptom of neuromyelitis optica spectrum disorder (NMOSD), and its diagnosis relies on clinical signs, imaging, and the presence of aquaporin-4 antibodies, which trigger an autoimmune response against astrocytes.

Recent phase III clinical trials have shown that three new biologics—eculizumab, inebilizumab, and satralizumab—are safe and effective treatments for NMOSD, targeting the complement system, CD19 B-cells, and the IL6 receptor, respectively, and have been approved for use in multiple countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What's new in neuromyelitis optica spectrum disorder treatment? Chu, YC., Huang, TL.[2022]

A study of 15 adults with idiopathic acute bilateral optic neuritis showed that corticosteroid therapy (intravenous methylprednisolone followed by oral prednisone) led to significant visual recovery, with average visual acuity improving from 1.71 to 0.36 after treatment.

No patients developed neurological problems during a follow-up period averaging 11 months, suggesting that while acute bilateral optic neuritis can occur without a known cause, it is generally associated with a favorable prognosis when treated with steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical profile of simultaneous bilateral optic neuritis in adults. de la Cruz, J., Kupersmith, MJ.[2022]

In a case study of a patient with MOG antibody disease, dimethyl fumarate was found to be ineffective in preventing relapses, as the patient experienced mild optic neuritis after treatment.

Despite its ineffectiveness for MOG antibody disease, dimethyl fumarate did not show harmful effects compared to other disease-modifying drugs used for treating neuromyelitis optica, suggesting it may be a safer option in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl Fumarate Was Ineffective but Not Harmful for a Patient with Myelin Oligodendrocyte Glycoprotein Antibody Disease. Warabi, Y., Takahashi, T., Isozaki, E.[2020]

In a study of 25 patients with acute optic neuritis, treatment with Clemastine for 90 days resulted in a significant recovery of visual function, as indicated by improved visual evoked potential (VEP) measurements compared to the placebo group.

Patients receiving Clemastine experienced less loss of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness compared to those on placebo, suggesting that Clemastine may help protect against retinal damage in optic neuritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized control trial of evaluation of Clemastine effects on visual evoked potential, nerve fiber layer and ganglion cell layer complex in patients with optic neuritis. Moghaddasi, M., Nabovvati, M., Koushki, A., et al.[2021]

In a study of nine patients with optic neuritis treated with high-dose oral corticosteroids (methylprednisolone at 1000 mg/day for 3-5 days), significant improvements in visual acuity, contrast sensitivity, and visual field index were observed as early as day 4 after treatment began.

By day 90, visual acuity improved from an average of 40.1 letters at baseline to 80.3 letters, indicating that high-dose corticosteroids can lead to rapid and substantial recovery of visual function in optic neuritis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rapid improvement in visual function after high-dose oral corticosteroids in patients with inflammatory optic neuropathy]. Poujade, A., Le Page, E., Baudet, D., et al.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32145678/

Randomized control trial of evaluation of Clemastine ... In contrast to treatment group, RNFL and GCL thickness of most quadrants are decreased significantly after three months in patients with ON in control group ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02521311

NCT02521311 | Assessment of Clemastine Fumarate as a ... The primary outcome is to measure the effectiveness of clemastine relative to placebo at preventing the loss of retinal nerve fiber assessed via optical ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0303846720300846

Randomized control trial of evaluation of Clemastine ... Highlights · Thinning of GCL and RNFL happen within 1 and 3–6 months of optic neuritis. · Clemastine could reduce the chance of significant loss in GCL and RNFL.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02521311?cond=Cranial%20nerve%20examination&aggFilters=status:not%20rec%20ava&rank=7

Assessment of Clemastine Fumarate as a Remyelinating ... The primary outcome is to measure the effectiveness of clemastine relative to placebo at preventing the loss of retinal nerve fiber assessed via optical ...

5. withpower.com withpower.com/trial/clemastine-for-optic-neuritis-6a204

Clemastine for Optic Neuritis (ReCOVER Trial) In a study of 25 patients with acute optic neuritis, treatment with Clemastine for 90 days resulted in a significant recovery of visual function, as indicated ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38296293/

Measuring and predicting the effect of remyelinating ... The aim of this trial is to investigate the (long-term) remyelinating effects of clemastine fumarate in patients with MS and INO and to evaluate if treatment ...

7. mstrust.org.uk mstrust.org.uk/a-z/clemastine

Clemastine Treatment with clemastine resulted in a small improvement in the speed of the nerve impulse. The researchers interpret this as showing repair to ...