Clemastine fumarate treatment for eye movement issues in multiple sclerosis

Clemastine Fumarate as Remyelinating Treatment in Internuclear Ophthalmoparesis and Multiple Sclerosis

This study is testing if clemastine fumarate can improve eye movement problems in people with multiple sclerosis and internuclear ophthalmoparesis.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Amsterdam UMC, location VUmc (other)
• Locations: 1 site (Amsterdam)
• Trial ID: NCT05338450 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the long-term effects of clemastine fumarate as a remyelinating therapy for patients with multiple sclerosis (MS) and internuclear ophthalmoparesis (INO). The study employs a double-blind, randomized, placebo-controlled design over a 6-month treatment period, assessing improvements in eye movement dysconjugacy using infrared oculography. Additionally, it aims to determine if a response to fampridine can predict the efficacy of clemastine treatment in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with a clinically definite diagnosis of multiple sclerosis and confirmed internuclear ophthalmoparesis.

Not a fit: Patients who have experienced a clinical relapse of MS or have changed their immunomodulatory therapy within the last 6 months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve eye movement coordination and overall quality of life for patients with MS.

How similar studies have performed: Previous studies have shown promise in using clemastine for remyelination, but this specific approach in the context of INO is novel.

Eligibility criteria

Inclusion criteria:

* A clinically definite diagnosis of multiple sclerosis.
* Diagnosis of internuclear ophthalmoparesis determined by the first infrared oculography at screening with either cut-off of 1.174 of the versional dysconjugacy index area under the curve (VDI-AUC) of 15° saccades or 1.180 of the versional dysconjugacy index peak velocity/saccadic amplitude (VDI-PV/Am) of 15° saccades.
* Age 18-70 (inclusive)
* Use of disease modifying therapies is not a contraindication.
* Ability to understand the purpose and risks of the study and provide signed and dated informed consent.

Exclusion criteria:

MS-related exclusion criteria:

* Changes in immunomodulatory therapy for multiple sclerosis in the 6 months before inclusion into the study.
* Clinical relapse of MS or high dosage corticosteroid use within 30 days before inclusion into the study.

IMP and medication related exclusion criteria:

* Contraindications to clemastine use, such as known porphyria or hypersensitivity to clemastine, other antihistamines with a similar chemical structure or any of the excipients.
* Contraindications to fampridine use, such as hypersensitivity to fampridine or any of the excipients, history of epilepsy, kidney disease (GFR \<50 ml/min absolute contraindication; GFR = 50-80 ml/min relative contraindication), use of Organic Cation Transporter 2 (OCT2) inhibitors or history of significant cardiac arrhythmias or conduction block.
* Concomitant use of Fampridine or any other formulation of 4-aminopyridine (4AP) or diamino4ap that cannot be temporarily suspended prior to each study visit.
* Changes in the use of medication currently being investigated in remyelination trials within 6 months before screening, including but not limited to domperidone, liothyronine, quetiapine, testosterone and bazedoxifene.
* Non-incidental use of central nervous system depressants including but not limited to hypnotics, anxiolytics, monoamine-oxidase inhibitors (MAOI'S), tricyclic antidepressants, opioid analgesics and other antihistamines with sedating properties (e.g. promethazine).

Other medical history and concomitant disease exclusion criteria:

* History of significant cardiac conduction block.
* History of malignancy of any organ system (other than localized squamous or basal cell carcinoma of the skin or adequately treated cervical cancer), treated or untreated, within the past 3 years, regardless of whether there is evidence of local recurrence or metastases.
* Estimated glomerular filtration rate (eGFR) \< 50 ml/min/1.73 m2; AST, ALT, or alkaline phosphatase \> 2 times the upper limit of normal.
* Any ophthalmological disease which may prevent accurate infrared oculography assessment.
* Suicidal ideation or behaviour in 6 months prior to baseline.
* History of drug or alcohol abuse within the past year.
* Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal or other major diseases that in the PI's judgement may affect interpretation of study results or patient safety.
* History of or presence of clinically significant medical illness or laboratory abnormality that, in the opinion of the investigator would preclude participation in the study.

General exclusion criteria:

* Pregnancy at the time of inclusion into the study or planning on breastfeeding within the first 7 months after inclusion in the study.
* Involvement in other study protocol simultaneously without prior approval.
* Insufficient proficiency in reading Dutch.
* Unable or unwilling to suspend driving for a duration of 6 months.

Where this trial is running

Amsterdam

• Amsterdam UMC, location VUmc — Amsterdam, Netherlands (RECRUITING)

Study contacts

• Principal investigator: Axel Petzold, Dr. — Amsterdam UMC, location VUmc
• Study coordinator: Sam Hof, MSc

Conditions: Multiple Sclerosis, Internuclear Ophthalmoplegia, clemastine, fampridine, remyelination, eye-tracking, infrared oculography