Assessment of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

— ReBUILD  

Official title:

A Phase II Randomized, Double-Blind, Parallel-Group, Placebo Controlled Crossover Trial to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02040298
• Other study ID #: ReBUILD
• Status: Completed
• Phase: Phase 2
• Start date: January 2014
• Est. completion date: April 2016

Study information

• Verified date: September 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to assess clemastine as a remyelinating agent in patients with relapsing forms of multiple sclerosis. The study will also evaluate the tolerability of clemastine, originally approved as first-generation antihistamine, in patients with multiple sclerosis. Study procedures will include assessments for evidence of remyelination in the anterior visual pathway and in the brain using electrophysiologic techniques and magnetic resonance imaging. The study will also assess the robustness and stability of this clinical effect in patients taking clemastine for up to 3 months. Patients in this study can remain on their standard disease modifying treatment during the course of the study. However, patients cannot participate in any other investigational new drug research study concurrently.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: April 2016
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Relapsing remitting Multiple Sclerosis by 2010 Revised McDonald Criteria

• Age 18-60.

• Latency delay > 125 milliseconds on baseline full-field transient pattern reversal visual evoked potential (VEP) in at least one eye (electrophysiological evidence of demyelination)

• Retinal nerve fiber layer (RNFL) > 70 microns on Spectralis Domain Optical Coherence Topography (SD-OCT) in the same eye meeting criteria for latency delay (sufficient axons)

• No optic neuritis in prior 6 months

• Stable immunomodulatory therapy - no switch or planned switch in > 6 months and no change in doses in 30 days prior to screening

• Use of appropriate contraception during period of trial (females of child bearing potential)

• Understand and sign informed consent.

• Expanded disability status scale (EDSS) 0-6.0 (inclusive)

Exclusion Criteria:

• Major ophthalmologic disease / Concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia , etc).

• Myopia > -7 Diopters (Severe myopia)

• History of significant cardiac conduction block

• History of cancer

• Known optic neuritis in involved eye > 5 years ago OR disease duration > 15 years

• Suicidal ideation or behaviour in 6 months prior to screening

• Pregnancy, breastfeeding, or planning to become pregnant.

• Involved with other study protocol simultaneously without prior approval. 9. Concomitant use of Dalfampridine (4AP or diamino4AP) or any other formulation of 4AP or diamino4AP.

• Concomitant use of any other putative remyelinating therapy as determined by investigator.

• Treatment with corticosteroids within 30 days prior to screening

• Prior treatment with total lymphoid irradiation, T cell or T cell receptor vaccination

• Prior treatment with alemtuzumab, mitoxantrone, or cyclophosphamide

• Serum creatinine > 1.5 mg/dL; aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase > 2 times the upper limit of normal

• History of drug or alcohol abuse within the past year

• Untreated vitamin B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid (MMA) and homocysteine) or untreated hypothyroidism

• Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, psychiatric allergic, renal or other major diseases that in the PI's judgment 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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Clemastine
4mg tablet twice daily
• Placebo
Placebo tablet twice daily

Locations

Country	Name	City	State
United States	UCSF Multiple Sclerosis Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (2)

Fischer JS, LaRocca NG, Miller DM, Ritvo PG, Andrews H, Paty D. Recent developments in the assessment of quality of life in multiple sclerosis (MS). Mult Scler. 1999 Aug;5(4):251-9. Review. — View Citation

Green AJ, Gelfand JM, Cree BA, Bevan C, Boscardin WJ, Mei F, Inman J, Arnow S, Devereux M, Abounasr A, Nobuta H, Zhu A, Friessen M, Gerona R, von Büdingen HC, Henry RG, Hauser SL, Chan JR. Clemastine fumarate as a remyelinating therapy for multiple sclero — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum Creatinine Level	Blood sample will be collected at each visit to evaluate health status...	Baseline, 1 month, 3 month, 5 month
Other	Serum Triglyceride Level	Blood sample will be collected at each visit to evaluate health status.	Baseline, 1 month, 3 month, 5 month
Other	Vitamin B-12 Level	Blood sample will be collected at each visit to evaluate health status.	Baseline, 1 month, 3 month, 5 month
Other	Human Chorionic Gonadotropin (hCG) Level in Female Patients of Childbearing Potential	Blood and urine sample will be collected to assess pregnancy status of all female participants of child bearing potential.	Baseline, 1 month, 3 month, 5 month
Primary	Full Field Visual Evoked Potential (VEP)	The primary objective is to evaluate the efficacy of Clemastine relative to placebo for reducing P100 latencies on full field transient pattern reversal visual evoked potentials.Visual evoked potentials (VEP) are used primarily to measure the functional integrity of the visual pathways from the retina to the visual cortex of the brain. VEP latencies were collected at Baseline, Month 1, Month 3, and Month 5.	Treatment start to treatment end, up to 3 months.
Secondary	Tolerability of Clemastine in Multiple Sclerosis (MS) Patients	Will demonstrate the tolerability of Clemastine in this population. This will include special focus with regards to fatigue as this is a major symptom for patients suffering from multiple sclerosis.This will be assessed by administering a fatigue questionnaire called the Multidimensional Assessment of Fatigue (MAF) at all four visits throughout the study. MAF scale range is 0-50. Lower scores indicate lower levels of fatigue and higher scores indicate higher levels of fatigue.	Treatment start to treatment end, up to 3 months.
Secondary	Myelin Water Fraction (MWF) and Magnetization Transfer Ratios (MTR)	To evaluate the efficacy of Clemastine relative to placebo in increasing magnetization transfer ratios derived from magnetic resonance imaging (MRI) of the brain during the period of exposure to active treatment.; To evaluate the efficacy of Clemastine relative to placebo at reducing radial diffusivity derived from diffusion tensor imaging as assessed by magnetic resonance imaging (MRI) during the period of exposure to active medication.	Treatment start to treatment end, up to 3 months.
Secondary	Expanded Disability Status Scale (EDSS) Score	To evaluate the efficacy of Clemastine relative to placebo in reducing the EDSS score at 90 days compared to placebo (Group A) & at 150 days compared to day 90 (Group B). EDSS is an ordinal scale for assessing neurological impairment of MS based on a neurological examination. It consists of scores in each of seven functional systems (FS) & an ambulation score that are then combined to determine the EDSS [ranging from 0 (normal) to 10 (death due to MS)]. The FSs are the Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, & Cerebral functions. FSs & EDSS steps assessed in a standardized manner. EDSS is a widely used &accepted instrument to evaluate disability status at a given time & longitudinally, to assess disability progression in clinical studies in MS.	Start of treatment to end of treatment, up to 3 months

External Links

•   ReBUILD trial description University of California, San Francisco Multiple Sclerosis Center