Clemastine Fumarate as Remyelinating Treatment in Internuclear Ophthalmoparesis and Multiple Sclerosis (RESTORE)

This is an interventional treatment trial for Multiple Sclerosis focused on measuring clemastine, fampridine, remyelination, eye-tracking, infrared oculography Read More

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.