Clemastine for Optic Neuritis

(ReCOVER Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Ari Green, MD, MCR

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of California, San Francisco

Must not be taking: Remyelinating therapies

Disqualifiers: Diabetes, Cancer, Pregnancy, others

Prior Safety Data

Approved in 3 Jurisdictions

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.

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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.

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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

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California San Francisco San Francisco, CA

Who Is Running the Clinical Trial?

University of California, San Francisco Lead Sponsor

Moorfields Eye Hospital NHS Foundation Trust Collaborator

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] Optic neuritis (ON) is the most common cause of optic neuropathy; typically presenting with a unilateral visual loss in young adults, with incidence of 1-5 in 100,000 per year. We evaluated the effect of Clemastine, a first-generation and CNS (central nervous system)-penetrant H1 receptor antagonist on visual evoked potential (VEP), retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) complex in patients with optic neuritis.

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] Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis.

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

[Rapid improvement in visual function after high-dose oral corticosteroids in patients with inflammatory optic neuropathy]. [2017] To study the progression of visual acuity and visual function parameters in patients with optic neuritis (ON) treated with high-dose oral corticosteroid therapy.

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

What's new in neuromyelitis optica spectrum disorder treatment? [2022] Optic neuritis, an optic nerve inflammatory disease presenting with acute unilateral or bilateral visual loss, is one of the core symptoms of neuromyelitis optica spectrum disorder (NMOSD). The diagnosis of NMOSD-related optic neuritis is challenging, and it is mainly based on clinical presentation, optical coherence tomography, magnetic resonance imaging scans, and the status of serum aquaporin-4 antibodies. In the pathogenesis, aquaporin-4 antibodies target astrocytes in the optic nerves, spinal cord and some specific regions of the brain eliciting a devastating autoimmune response. Current pharmacological interventions are directed against various steps within the immunological response, notably the terminal complement system, B-cells, and the pro-inflammatory cytokine Interleukin 6 (IL6). Conventional maintenance therapies were off-label uses of the unspecific immunosuppressants azathioprine and mycophenolate mofetil as well as the CD20 specific antibody rituximab and the IL6 receptor specific antibody tocilizumab. Recently, four phase III clinical trials demonstrated the safety and efficacy of the three novel biologics eculizumab, inebilizumab, and satralizumab. These monoclonal antibodies are directed against the complement system, CD19 B-cells and the IL6 receptor, respectively. All three have been approved for NMOSD in the US and several other countries worldwide and thus provide convincing treatment options.

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

Clinical profile of simultaneous bilateral optic neuritis in adults. [2022] To establish the clinical profile of simultaneous bilateral optic neuritis in adults, the efficacy of steroid therapy, extent of visual recovery, and neurological outcome.

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] We treated a myelin oligodendrocyte glycoprotein (MOG) antibody disease patient who had been prescribed dimethyl fumarate because she was thought to have been suffering from multiple sclerosis (MS). Mild optic neuritis relapsed at one year and four months after the administration of dimethyl fumarate. Therefore, dimethyl fumarate was ineffective for preventing relapse of MOG antibody disease. However, dimethyl fumarate for MOG antibody disease was not harmful compared with when disease-modifying drugs (DMDs) of MS were used for anti-aquaporin-4 antibody-positive neuromyelitis optica. If MS patients repeat relapses even after the start of DMDs, a differential diagnosis including MOG antibody disease should be made.

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

[National clinical investigation of anti-aquaporin-4 seropositive optic neuritis]. [2015] We carried out a national clinical investigation of anti-aquaporin-4 seropositive optic neuritis which is resistant to steroid pulse therapy.