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

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to assess clemastine as a remyelinating agent in patients with acute optic neuritis.The study will also evaluate the tolerability of clemastine, originally approved as first-generation antihistamine, in patients with optic neuritis. Study procedures will include assessments for evidence of remyelination in the anterior visual pathway and in the brain using electrophysiologic techniques and magnetic resonance imaging. If they are on one, patients in this study can remain on their standard disease modifying treatment during the course of the study. However, patients cannot participate in any other investigational new drug research study concurrently.

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.

What data supports the effectiveness of the drug Clemastine for treating optic neuritis?

Research shows that Clemastine, a drug that affects the central nervous system, has been studied for its impact on visual functions in patients with optic neuritis. Additionally, Clemastine fumarate has shown promise in stimulating myelin repair in multiple sclerosis, which is related to nerve protection and could suggest potential benefits for optic neuritis. ^{1 2 3 4 5}

How does the drug Clemastine differ from other treatments for optic neuritis?

Clemastine is unique because it is a first-generation antihistamine that can penetrate the central nervous system and may help repair myelin, the protective covering of nerves, which is not a typical approach for treating optic neuritis. ^{1 2 4 6 7}

Research Team

Ari Green, MD, MCR

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

References

1. Netherlands 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Rapid improvement in visual function after high-dose oral corticosteroids in patients with inflammatory optic neuropathy]. [2017]

4. India pubmed.ncbi.nlm.nih.gov

What's new in neuromyelitis optica spectrum disorder treatment? [2022]

5. England pubmed.ncbi.nlm.nih.gov

Clinical profile of simultaneous bilateral optic neuritis in adults. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Dimethyl Fumarate Was Ineffective but Not Harmful for a Patient with Myelin Oligodendrocyte Glycoprotein Antibody Disease. [2020]

7. Japan pubmed.ncbi.nlm.nih.gov

[National clinical investigation of anti-aquaporin-4 seropositive optic neuritis]. [2015]