Clinical Trial: Assessment of Clemastine Fumarate as a Remyelinating Agent in Acute Optic Neuritis (ReCOVER)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomized, Double-Blind, Parallel-Group, Placebo Controlled Trial to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Clemastine Fumarate as a Remyelinating Agent in Acute Optic N

Brief Summary: The main purpose of this study is to assess clemastine as a remyelinating agent in patients with acute optic neuritis.The study will also evaluate the tolerability of clemastine, originally approved as first-generation antihistamine, in patients with optic neuritis. 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. If they are on one, 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.

Detailed Summary:
Sponsor: University of California, San Francisco

Current Primary Outcome:

• Change in P100 latency on full-field visual evoked potential [ Time Frame: baseline, 1 week, 1 month, 3 months, 9 months ]
  To evaluate the efficacy of clemastine relative to placebo for reducing P100 latencies on full field transient pattern reversal visual evoked potentials. Measure will be reported as difference in P100 latency from baseline to 9 months.
• Change in low contrast visual acuity [ Time Frame: baseline, 1 week, 1 month, 3 months, 9 months ]
  The second primary outcome is to measure the effectiveness of clemastine relative to placebo at improving patient performance on ETDRS low contrast visual acuity chart testing (2.5% black on white) during the recovery from an acute optic neuritis. Measure will be reported as difference in ETDRS score from baseline to 9 months.

Original Primary Outcome:

• Change in retinal nerve fiber layer thickness on optical coherence tomography [ Time Frame: baseline, 1 week, 1 month, 3 months, 9 months ]
  The primary outcome is to measure the effectiveness of clemastine relative to placebo at preventing the loss of retinal nerve fiber assessed via optical coherence tomography (OCT). Measure will be reported as difference in nerve fiber thickness between baseline and 9 months.
• Change in low contrast visual acuity [ Time Frame: baseline, 1 week, 1 month, 3 months, 9 months ]
  The second primary outcome is to measure the effectiveness of clemastine relative to placebo at improving patient performance on ETDRS low contrast visual acuity chart testing (2.5% black on white) during the recovery from an acute optic neuritis. Measure will be reported as difference in ETDRS score from baseline to 9 months.

Current Secondary Outcome:

• Change in retinal nerve fiber layer thickness on optical coherence tomography [ Time Frame: baseline, 1 week, 1 month, 3 months, 9 months ]
  The primary outcome is to measure the effectiveness of clemastine relative to placebo at preventing the loss of retinal nerve fiber assessed via optical coherence tomography (OCT). Measure will be reported as difference in nerve fiber thickness between baseline and 9 months.
• Radiological outcomes assessed by magnetic resonance imaging [ Time Frame: baseline, 9 month ]
  To evaluate the efficacy of clemastine relative to placebo in increasing magnetization transfer ratios and myelin water fraction derived from magnetic resonance imaging of the brain during the period of exposure to active treatment. Measures will be reported as change between baseline and 9 months.
• Pupillary light response: pupillometry [ Time Frame: baseline, 1-week, 1-month, 3-month, 5-month ]
  To use pupillometry to evaluate the effectiveness of Clemastine in preventing a decreased light response in optic neuritis. Pupillometry has been shown to be an effective and sensitive way to evaluate changes in optic nerve function. Measure will be reported as the difference in light sensitivity as evaluated by pupillometry at baseline and 9 months.
• Expanded Disability Status Scale score [ Time Frame: baseline, 9 months ]
  To evaluate the efficacy of Clemastine relative to placebo in reducing the EDSS score at 9 months.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.

Original Secondary Outcome:

• Change in P100 latency on full-field visual evoked potential [ Time Frame: baseline, 3 months, 9 months ]
  To evaluate the efficacy of clemastine relative to placebo for reducing P100 latencies on full field transient pattern reversal visual evoked potentials. Measure will be reported as difference in P100 latency from baseline to 9 months.
• Radiological outcomes assessed by magnetic resonance imaging [ Time Frame: baseline, 9 month ]
  To evaluate the efficacy of clemastine relative to placebo in increasing magnetization transfer ratios and myelin water fraction derived from magnetic resonance imaging of the brain during the period of exposure to active treatment. Measures will be reported as change between baseline and 9 months.
• Pupillary light response: pupillometry [ Time Frame: baseline, 1-week, 1-month, 3-month, 5-month ]
  To use pupillometry to evaluate the effectiveness of Clemastine in preventing a decreased light response in optic neuritis. Pupillometry has been shown to be an effective and sensitive way to evaluate changes in optic nerve function. Measure will be reported as the difference in light sensitivity as evaluated by pupillometry at baseline and 9 months.
• Expanded Disability Status Scale score [ Time Frame: baseline, 9 months ]
  To evaluate the efficacy of Clemastine relative to placebo in reducing the EDSS score at 9 months.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.

Dates:
Date Received: August 10, 2015
Date Started: August 2016
Date Completion: January 2018
Last Updated: March 13, 2017
Last Verified: March 2017