Clemastine fumarate as remyelinating treatment in internuclear ophthalmoparesis and multiple sclerosis

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 80

Inclusion Criteria

1. A clinically definite diagnosis of multiple sclerosis.
2. 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.
3. Age 18-70 (inclusive)
4. Use of disease modifying therapies is not a contraindication.
5. Ability to understand the purpose and risks of the study and provide signed
and dated informed consent.

Exclusion Criteria

MS-related exclusion criteria:
1. Changes in immunomodulatory therapy for multiple sclerosis in the 6 months
before inclusion into the study.
2. Clinical relapse of MS or high dosage corticosteroid use within 30 days
before inclusion into the study.

IMP and medication related exclusion criteria:
3. Contraindications to clemastine use, such as known porphyria or
hypersensitivity to clemastine, other antihistamines with a similar chemical
structure or any of the excipients.
4. 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.
5. Concomitant use of Fampridine or any other formulation of 4-aminopyridine
(4AP) or diamino4ap that cannot be temporarily suspended prior to each study
visit.
6. 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.
7. 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:
8. History of significant cardiac conduction block.
9. 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.
10. Estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2; AST, ALT,
or alkaline phosphatase > 3 times the upper limit of normal.
11. Any ophthalmological disease which may prevent accurate infrared
oculography assessment.
12. Suicidal ideation or behaviour in 6 months prior to baseline.
13. History of drug or alcohol abuse within the past year.
14. 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.
15. 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:
16. Pregnancy at the time of inclusion into the study or planning on
breastfeeding within the first 7 months after inclusion in the study.
17. Involvement in other study protocol simultaneously without prior approval.
18. Insufficient proficiency in reading Dutch or English.
19. Unable or unwilling to suspend driving for a duration of 6 months.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary outcome measure is the change in versional dysconjugacy index (VDI)<br /><br>of area under the curve (AUC) measured by infrared oculography.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary outcome measures include changes in other VDI measures (peak velocity<br /><br>per amplitude (PV/Am) and peak velocity (PV)), changes in VDI after single<br /><br>fampridine dose, other oculography parameters (e.g. saccadic latency,<br /><br>anti-saccades), (peripheral) retinal nerve fibre layer (pRNFL) and (macular)<br /><br>ganglion cell inner plexiform layer (mGCIPL) thickness measured by Optical<br /><br>Coherence Tomography (OCT), Symbol Digit Modalities Test (SDMT), Expanded<br /><br>Disability Status Scale (EDSS), high and low contrast visual acuity, subjective<br /><br>visual functioning (NEI-VFQ-25 and NOV-AU questionnaire), quality of life<br /><br>(EQ5D-5L) and fatigue (CIS20R and NFI-MS questionnaire).</p><br>

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