Assessment of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis (ReBUILD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02040298
First received: January 10, 2014
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis, Relapsing-Remitting
Drug: Clemastine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Full Field Visual Evoked Potential [ Time Frame: Baseline, 1 month, 3 month, 5 month ] [ Designated as safety issue: No ]
    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. VEPs are used primarily to measure the functional integrity of the visual pathways from the retina to the visual cortex of the brain.


Secondary Outcome Measures:
  • Tolerability of Clemastine in Multiple Sclerosis Patients [ Time Frame: Baseline, 1 month, 3 month, 5 month ] [ Designated as safety issue: No ]
    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 at all four visits throughout the study.

  • Myelin Water Volume and Magnetization Transfer Ratios [ Time Frame: Baseline, 3 month, 5 month time points ] [ Designated as safety issue: No ]

    To evaluate the efficacy of Clemastine relative to placebo in increasing magnetization transfer ratios derived from magnetic resonance imaging 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 during the period of exposure to active medication.


  • Expanded Disability Status Scale score [ Time Frame: Baseline, 3 months, 5 months ] [ Designated as safety issue: No ]

    To evaluate the efficacy of Clemastine relative to placebo in reducing the EDSS score at 90 days compared to placebo (Group A) and at 150 days compared to day 90 (Group B).

    The EDSS is an ordinal scale used for assessing neurological impairment of MS based on a neurological examination. It consists of scores in each of seven functional systems (FS) and 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, and Cerebral functions. The FSs and EDSS steps will be assessed in a standardized manner. EDSS is a widely used and accepted instrument to evaluate disability status at a given time and longitudinally, to assess disability progression in clinical studies in MS.



Other Outcome Measures:
  • Serum Creatinine Level [ Time Frame: Baseline, 1 month, 3 month, 5 month ] [ Designated as safety issue: Yes ]
    Blood sample will be collected at each visit to evaluate health status.

  • Serum Triglyceride Level [ Time Frame: Baseline, 1 month, 3 month, 5 month ] [ Designated as safety issue: Yes ]
    Blood sample will be collected at each visit to evaluate health status.

  • Vitamin B-12 Level [ Time Frame: Baseline, 1 month, 3 month, 5 month ] [ Designated as safety issue: Yes ]
    Blood sample will be collected at each visit to evaluate health status.

  • Human Chorionic Gonadotropin (hCG) level in Female patients of Childbearing potential [ Time Frame: Baseline, 1 month, 3 month, 5 month ] [ Designated as safety issue: Yes ]
    Blood and urine sample will be collected to assess pregnancy status of all female participants of child bearing potential.

  • Number of Patients with Adverse Events [ Time Frame: 1 month, 3 month, 5 month from baseline ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: January 2014
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 3 months Clemastine, 2 months Placebo
4mg clemastine twice daily for first 3 months -- crossover -- equivalent quantity/frequncy of placebo for last 2 months
Drug: Clemastine
4mg tablet twice daily
Other Names:
  • Clemastine Fumarate,
  • Tavist -1
Drug: Placebo
Placebo tablet twice daily
Other Name: Placebo
Active Comparator: 3 months Placebo , 2 months Clemastine
Placebo for first 3 months -- crossover -- 4mg clemastine twice daily for last 2 months.
Drug: Clemastine
4mg tablet twice daily
Other Names:
  • Clemastine Fumarate,
  • Tavist -1
Drug: Placebo
Placebo tablet twice daily
Other Name: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 VEP in at least one eye (electrophysiological evidence of demyelination)
  • RNFL > 70 microns on 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.
  • 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 Dalfamprdine 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 alemtuzamab, mitoxantrone, or cyclophosphamide
  • Serum creatinine > 1.5 mg/dL; AST, ALT or alkaline phosphatase > 2 times the upper limit of normal
  • History of drug or alcohol abuse within the past year
  • Untreated 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02040298

Contacts
Contact: Aya Abounasr, BS 415-502-7204 aya.abounasr@ucsf.edu
Contact: Sam Arnow, BS Samuel.Arnow@ucsf.edu

Locations
United States, California
UCSF Multiple Sclerosis Center Recruiting
San Francisco, California, United States, 94518
Contact: Sam Arnow, BS    415-353-2707    samuel.arnow@ucsf.edu   
Contact: Justin Inman, BS       justin.inman@ucsf.edu   
Principal Investigator: Ari J Green, MD, MCR         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Ari J. Green, MD, MCR University of California, San Francisco
  More Information

Additional Information:
Publications:
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02040298     History of Changes
Other Study ID Numbers: ReBUILD
Study First Received: January 10, 2014
Last Updated: July 10, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Clemastine
Antipruritics
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Allergic Agents

ClinicalTrials.gov processed this record on September 16, 2014