Assessment of Clemastine Fumarate as a Remyelinating Agent in Acute Optic Neuritis (ReCOVER)

NCT ID: NCT02521311

Last Updated: 2024-07-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-28
• Study Completion Date: 2026-08-31

Brief Summary

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.

Detailed Description

Optic neuritis is an inflammatory, demyelinating disease of the optic nerve. It is most often characterized by visual loss or blurred vision along with dyschromatopsiaaccompanied by pain (especially with eye movement) and no demonstrable evidence of an alternate diagnosis such as ischemia or retinal disease. It can also be associated with a swollen optic disc (Optic Neuritis Study Group 1991, Hutchinson, W.M. 1976) and optic nerve enhancement on MRI (Kupersmith 2002).

Functional high-throughput screening for compounds that promote remyelination presents a major unmet need in the therapeutic arsenal for multiple sclerosis and other demyelinating conditions such as optic neuritis. Screening for myelin repair is problematic, as functional remyelination requires the presence of intact neuronal axons. Standard methods are not suited for high-throughput formats. We performed a detailed screen of over 1500 FDA approved small molecule drugs to identify agents that could be promising for remyelination. Engineered with conical dimensions, our micropillar technology permitted resolution of the extent and length of membrane wrapping from a single 2-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for the fluorescence detection of concentric wrapping observed as "rings" of myelin membrane. The platform was formatted in 96-well plates, amenable to semi-automated random acquisition and automated detection and quantification. Upon initiating a screen of 1500 bioactive molecules, we identified Clemastine as a compound that potentially enhances oligodendrocyte differentiation and remyelination. We then validated this and other drugs in preclinical assays as well as in animal models of primary myelination and remyelination after inflammatory and chemical demyelination. Together, our findings illustrate the proof of concept for a novel high-throughput screening platform for potential regenerative therapeutics in MS (Chan JR et al. 2014).

This study is intended to assess for clinical evidence of remyelination using Clemastine Fumarate in patients with acute inflammatory injury causing demyelination of the anterior visual pathway as a consequence of acute demyelinating optic neuritis. The study is designed to assess tolerability and clinical efficacy of Clemastine using outcomes intended to assess for (a) adverse events and (b) recovery of myelin. This study is complementary to an earlier study evaluating clemastine in chronic demyelinated optic neuropathy and serves as part of a proof of concept program intended to evaluate methods for conducting remyelination trials in MS.

Conditions

Optic Neuritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Clemastine

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

Group Type: EXPERIMENTAL

Clemastine

Intervention Type: DRUG

12mg (4mg 3x/day) clemastine for 7 days followed by 8mg clemastine (4mg 2x/day) until 3 months. Patients will be off treatment from 3-9 months and will be reevaluated at 9 months.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Equivalent placebo. 12mg (4mg 3x/day) placebo for 7 days followed by 8mg placebo (4mg 2x/day) until 3 months. Patients will be off treatment from 3-9 months and will be reevaluated at 9 months.

Interventions

Clemastine

12mg (4mg 3x/day) clemastine for 7 days followed by 8mg clemastine (4mg 2x/day) until 3 months. Patients will be off treatment from 3-9 months and will be reevaluated at 9 months.

Intervention Type: DRUG

Placebo

Equivalent placebo. 12mg (4mg 3x/day) placebo for 7 days followed by 8mg placebo (4mg 2x/day) until 3 months. Patients will be off treatment from 3-9 months and will be reevaluated at 9 months.

Intervention Type: DRUG

Other Intervention Names

Tavist; Clemastine fumarate; Walhist

Eligibility Criteria

Inclusion Criteria

• Patients diagnosed or suspected to have an acute demyelinating optic neuritis in at least one eye within 3 weeks from the onset of any visual symptom other than pain
• Use of disease-modifying therapies is not a contraindication
• Use of appropriate contraception during the period of trial (women)
• Understand and sign the informed consent

Exclusion Criteria

• Other major ophthalmologic diseases / concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia, etc)
• Disc hemorrhages in the qualifying eye
• No light perception in qualifying eye
• Simultaneous bilateral optic neuritis
• Cotton wool spots in the qualifying eye
• Macular star in the qualifying eye
• History of significant cardiac conduction block
• History of cancer
• Suicidal ideation or behavior in 6 months prior to baseline
• Pregnancy, breastfeeding or planning to become pregnant
• Involved with other study protocols simultaneously without prior approval
• Concomitant use of any other putative remyelinating therapy as determined by the investigator
• Serum creatinine > 1.5 mg/dL; aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase > 2 times the upper limit of normal
• History of drug or alcohol abuse within the past year
• Untreated B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid (MMA) and homocysteine) or untreated hypothyroidism
• Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal, or other major diseases that, in the PI's judgment, may affect the interpretation of study results or patient safety
• History or presence of clinically significant medical illness or laboratory abnormality that, in the opinion of the investigator would preclude participation in the study.
• Positive for NMO antibody discovered within the first 2 weeks after randomization.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Moorfields Eye Hospital NHS Foundation Trust

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ari Green, MD, MCR

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California San Francisco

San Francisco, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Harkeerat Halait

Role: CONTACT

Harkeerat.Halait@ucsf.edu

415.353.2707

Angelica Montevirgen, BS

Role: CONTACT

Angelica.Montevirgen@ucsf.edu

415.745.1304

Facility Contacts

Harkeerat Halait

Role: primary

Harkeerat.Halait@ucsf.edu

415-353-2707

Angelica Montevirgen, BS

Role: backup

Angelica.Montevirgen@ucsf.edu

415.745.1304

References

Mei F, Fancy SPJ, Shen YA, Niu J, Zhao C, Presley B, Miao E, Lee S, Mayoral SR, Redmond SA, Etxeberria A, Xiao L, Franklin RJM, Green A, Hauser SL, Chan JR. Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med. 2014 Aug;20(8):954-960. doi: 10.1038/nm.3618. Epub 2014 Jul 6.

Reference Type: BACKGROUND

PMID: 24997607 (View on PubMed)

Other Identifiers

15-17428

Identifier Type: -

Identifier Source: org_study_id