Clemastine Fumarate as Remyelinating Treatment in Internuclear Ophthalmoparesis and Multiple Sclerosis
- Conditions
- Multiple SclerosisInternuclear Ophthalmoplegia
- Interventions
- Drug: Placebo
- Registration Number
- NCT05338450
- Lead Sponsor
- Amsterdam UMC, location VUmc
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Clemastine Fumarate Clemastine Fumarate - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Versional Dysconjugacy Index (VDI) - Area Under the Curve (VDI-AUC) (36 months) 36 months The relative change in VDI from baseline will be compared between the treatment and control group at the end of follow-up (36 months).
Versional Dysconjugacy Index (VDI) - Area Under the Curve (VDI-AUC) (6 months) 6 months Our main study parameter is the versional dysconjugacy index (VDI) measured by infrared oculography. The relative change in VDI from baseline will be compared between the treatment and control group at the end of treatment (6 months). The VDI of Area Under the Curve (AUC) will be our primary study parameter. This describes the area under the saccadic trajectory of the horizontal eye position.
- Secondary Outcome Measures
Name Time Method Symbol Digit Modalities Test (SDMT) 6 months and 36 months Subjective visual functioning (NEI-VFQ-25) 6 months and 36 months Changes in subjective visual functioning measured by the National Eye Institute Visual Functioning Questionnaire - 25 (NEI-VFQ-25) questionnaire.
Fatigue - NFI-MS 6 months and 36 months Prevalence and changes in fatigue measured by the Neurological Fatigue Index MS (NFI-MS) questionnaire.
High and Low Contrast Visual Acuity (HCVA and LCVA) 6 months and 36 months Versional Dysconjugacy Index (VDI) - Response to Fampridine Baseline Changes in VDI in response to single dose of Fampridine.
Quality of life (EQ5D-5L) 6 months and 36 months Changes in quality of life measured by EuroQol 5-Dimension 5-Level (EQ5D-5L) questionnaire.
Other Versional Dysconjugacy Index (VDI) measures - Peak Velocity (VDI-pV + VDI-pV/Am) 6 and 36 months Changes in other VDI measures (peak velocity (PV) and peak velocity divided by amplitude (PV/Am)).
Other infrared oculography parameters - Saccadic Latency 6 months and 36 months Changes in saccadic latency measured by infrared oculography.
Other infrared oculography parameters - Proportion of errors in an anti-saccadic task 6 months and 36 months Changes in proportion of errors in an anti-saccadic task measured by infrared oculography.
Other infrared oculography parameters - Proportion of correct double-step saccades 6 months and 36 months Changes in the proportion of correct double-step saccades measured by infrared oculography.
Expanded Disability Status Scale (EDSS) 6 months and 36 months Changes in the Expanded Disability Status Scale (EDSS), which ranges from 0 (normal neurological exam, no disability) to 10.0 (death due to MS).
Other infrared oculography parameters - Error of the final eye position in double-step saccades 6 months and 36 months Changes in the error of the final eye position in double-step saccades measured by infrared oculography.
Visual complaints (NOV-AU) 6 months and 36 months Changes in visual complaints measured by the Neuro-Ophthalmology Questionnaire Amsterdam UMC (NOV-AU) questionnaire.
Fatigue - CIS20R 6 months and 36 months Prevalence and changes in fatigue measured by the Checklist Individual Strength (CIS20R) questionnaire.
Trial Locations
- Locations (1)
Amsterdam UMC, location VUmc
🇳🇱Amsterdam, Netherlands