Multiple sclerosis (MS) Internuclear ophthalmoparesis (INO) MedDRA version: 21.0 Level: LLT Classification code 10080865 Term: Multiple sclerosis lesion System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Clemastine Milstein 1 mg, tabletten
Product Name: Clemastine fumarate
Pharmaceutical Form: Tablet
INN or Proposed INN: CLEMASTINE FUMARATE
CAS Number: 14976-57-9
Concentration unit: mg mil
Sponsors
Amsterdam University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 71 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: -To evaluate whether dysconjugacy reduction after a single-dose Fampridine trial prior to treatment with clemastine can predict treatment response to clemastine. -To investigate whether treatment with clemastine can induce long term protection against degeneration of retinal layers. -To evaluate the effect of clemastine on other eye movement parameters assessed by infrared oculography, such as latency of saccades and proportion of errors in an anti-saccadic task. -To evaluate the effect of clemastine on cognition and general disability in MS. -To evaluate the effect of clemastine treatment on low and high contrast visual acuity. -To evaluate the effect of clemastine treatment on reported subjective visual functioning, fatigue and quality of life. ;Primary end point(s): 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) and multiple follow-up periods (12, 24 and 36 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. Other VDI measures (PV, Pv/Am) will be included in the secondary study parameters.;Timepoint(s) of evaluation of this end point: The relative change in VDI 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). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Changes in other VDI measures (peak velocity (PV) and peak velocity divided by amplitude (PV/Am)). - Changes in VDI in response to single dose of Fampridine. - Changes in other eye movement parameters measured by infrared oculography, such as: saccade latency, proportion of errors in an anti-saccadic task, proportion of correct double-step saccades and error of the final eye position and infrared pupillary asymmetry - Changes in retinal layer thickness on longitudinal OCT, such as (peripheral) retinal nerve fibre layer (pRNFL) and (macular) ganglion cell inner plexiform layer (mGCIPL). - Changes in SDMT. - Changes in EDSS. - Changes in high and low contrast visual acuity (HCVA and LCVA). - Changes in subjective visual functioning visual complaints measured by NEI-VFQ-25 and NOV-AU. - Changes in quality of life measured by EQ5D-5L. - Prevalence and changes in fatigue measured by CIS20R and NFI-MS. ;Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated at the end of treatment (6 months) and multiple follow-up periods (12, 24 and 36 months). | — |
Countries
Netherlands
Contacts
Public ContactInvestigators Office
MS Center Amsterdam
Outcome results
None listed