Clemastine fumarate as remyelinating treatment in internuclear ophthalmoparesis and multiple sclerosis

Phase 3

Active, not recruiting

• Conditions: Internuclear ophthalmoparesis; Multiple sclerosis

• Registration Number: 2024-513099-17-00
• Lead Sponsor: Amsterdam UMC Stichting

Brief Summary

Our primary objective is to longitudinally evaluate the efficacy of clemastine fumarate to reduce dysconjugacy of horizontal eye movements measured by infrared oculography in patients with MS and internuclear ophthalmoplegia (INO) and to evaluate whether effects meaningfully persist after treatment, representing lasting remyelination.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-08-14
• Last Update Posted: 2025-01-30

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 80

Inclusion Criteria

A clinically definite diagnosis of multiple sclerosis

Diagnosis of internuclear ophthalmoplegia 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

Changes in immunomodulatory therapy for multiple sclerosis in the 6 months before inclusion into the study

Estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2; AST, ALT, or alkaline phosphatase > 3 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.

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 or English.

Unable or unwilling to suspend driving for a duration of 6 months.

Clinical relapse of MS or high dosage corticosteroid use within 30 days before inclusion into the study.

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).

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The relative change in Versional Dysconjugacy Index (VDI) of Area under the Curve (AUC) from baseline will be compared between the treatment and control group at the end of treatment (6 months) and multiple follow-up periods (12, 24 and 36 months)		The relative change in Versional Dysconjugacy Index (VDI) of Area under the Curve (AUC) from baseline will be compared between the treatment and control group at the end of treatment (6 months) and multiple follow-up periods (12, 24 and 36 months)

Trial Locations

Locations (1)

VUmc Stichting; 🇳🇱 Amsterdam, Netherlands

VUmc Stichting

🇳🇱Amsterdam, Netherlands

Axel Petzold

Site contact

+31204441160

a.petzold@amsterdamumc.nl