Clemastine Fumarate as Remyelinating Treatment in Internuclear Ophthalmoparesis and Multiple Sclerosis
Status:
Not yet recruiting
Trial end date:
2026-11-01
Target enrollment:
Participant gender:
Summary
Rationale: Clemastine fumarate has been identified as potential remyelinating therapy for
multiple sclerosis (MS). The (long-term) effects of clemastine need to be confirmed in
clinical models for MS. Internuclear ophthalmoparesis (INO) may be used as a clinical model
for investigating remyelinating therapies by measuring horizontal eye movements with infrared
oculography. Furthermore, infrared oculography combined with a single dose of fampridine may
be used to identify individuals with MS that are most likely to benefit from remyelinating
therapy.
Objective: To assess the (long-term) efficacy of clemastine fumarate in improving
dysconjugacy of eye movements in patients with internuclear ophthalmoparesis and multiple
sclerosis. Secondly, to assess whether a response to a single dose of fampridine can predict
the effects of clemastine treatment.
Study design: A single-centre double-blind randomized placebo-controlled trial consisting of
a 6 months (180 days) treatment period followed by a 30 months follow-up period.
Study population: 80 MS patients, age 18-70 years, with INO.
Intervention: The intervention group will receive 4 mg of clemastine fumarate twice daily (8
mg/day) for 6 months (180 days), the control group will receive an equivalent amount of
placebo. At baseline all participants will receive a single 10 mg dose of fampridine.
Main study parameters/endpoints: The primary outcome measure is the change in versional
dysconjugacy index (VDI) of area under the curve (AUC) measured by infrared oculography.
Secondary outcome measures include changes in other VDI measures (peak velocity per amplitude
(PV/Am) and peak velocity (PV)), changes in VDI after single fampridine dose, other
oculography parameters (e.g. saccadic latency, anti-saccades), (peripheral) retinal nerve
fibre layer (pRNFL) and (macular) ganglion cell inner plexiform layer (mGCIPL) thickness
measured by OCT, SDMT, EDSS, high and low contrast visual acuity, subjective visual
functioning (NEI-VFQ-25 and NOV-AU questionnaire), quality of life (EQ5D-5L) and fatigue
(CIS20R and NFI-MS questionnaire).
Nature and extent of the burden and risks: Participation in the study will consist of a total
of 7 study visits. Study visits will include physical/neurological examination, infrared
oculography, OCT, visual acuity tests, a cognition test (SDMT), 5 questionnaires and blood
samples for safety laboratory tests. Considering both clemastine and fampridine are
registered and well-established drugs and have been used in clinical practice, the estimated
risk of unexpected adverse reactions is low.