Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple Sclerosis

NCT02391961 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: F1180-W1IK2RX001180-01A2
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Primary fatigue represents a major cause of disability in patients with multiple sclerosis (MS), being reported in about 90% of cases. Fatigue interferes with everyday functioning but, unfortunately, little is known about its mechanisms. The investigators propose a characteristic eye movement abnormality (internuclear ophthalmoparesis, INO), commonly encountered in MS, as a simple model for primary motor fatigue. The investigators described worsening of ocular performance in MS patients with INO following visual tasks (ocular motor fatigue), which is likely due to decreased neural conduction along brain pathways injured by MS. This mechanism could represent a major component of MS-related primary motor fatigue. Relevant to Veterans' care, INO is a significant cause of visual disability, especially when complicated by ocular fatigue, and limits daily activities such as reading and driving. The investigators propose a medical treatment to improve ocular performance/fatigue in INO, which can reduce visual disability and improve quality of life in Veterans with MS.

Conditions

Multiple Sclerosis; Internuclear Ophthalmoplegia; Fatigue

Outcome Measures

Primary Outcomes (2)

• Pulse Size Ratio (PSR): Abducting/Adducting Eye Ratio for Saccadic Peak Velocity.

  For each saccade made by the subject, the ratio of the maximum velocity (deg/sec) of the eye moving away from the nose and of the eye moving towards the nose was calculated. Subjects' horizontal saccades were recorded for 10 minutes, and an average of PSR for all saccades recorded was taken.

  Average PSR values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

• Pulse Time Delay (PTD): Time Difference Between Onset of the Saccade in the Adducting Eye and Onset of the Saccade in the Abducting Eye.

  For each saccade made by the subject, we calculated the difference (in sec) between the onset (based on a velocity threshold) of the movement in the adducting eye (the eye moving towards the nose) and the onset of the movement in the abducting eye (the eye moving away from the nose). Subjects' horizontal saccades were recorded for 10 minutes, and an average of PTD for all saccades recorded was taken.

  Average PTD values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

Secondary Outcomes (5)

• Reading Acuity (RA)

  Average RA values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

• Maximum Reading Speed (MRS)

  Average MRS values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

• Gait Assessment

  Measures were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

• National Eye Institute (NEI) Visual Function Questionnaire 25 (VFQ-25)

  VFQ25 was administered on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks).

• 10-Item Neuro-Ophthalmic Supplement (NOS)

  10-Item NOS was administered on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks).

Study Arms (2)

dalfampridine

EXPERIMENTAL

10-week randomized, placebo controlled, double-blind, crossover trial, which includes a period of wash out of two weeks between treatment with dalfampridine and placebo. Within the trial, each patient serves as his own control.

Drug: Dalfampridine

placebo

PLACEBO COMPARATOR

10-week randomized, placebo controlled, double-blind, crossover trial, which includes a period of wash out of two weeks between treatment with dalfampridine and placebo. Within the trial, each patient serves as his own control.

Drug: Placebo

Interventions

Dalfampridine DRUG

10-week randomized, placebo controlled, double-blind, crossover trial, which includes a period of wash out of two weeks between treatment with dalfampridine and placebo.

dalfampridine

Placebo DRUG

10-week randomized, placebo controlled, double-blind, crossover trial, which includes a period of wash out of two weeks between treatment with dalfampridine and placebo.

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of MS of any course and duration
• Evidence of mild to moderate internuclear ophthalmoparesis (INO), that is slowing of the adducting eye on physical examination of saccadic speed, whether INO is unilateral or bilateral, symmetrical or asymmetrical
• Medically stable conditions, ability to give informed consent and understand and cooperate with the testing
• Dalfampridine-naive as well as history of taking dalfampridine in the past, whether there was benefit in gait impairment or not, after a washout period of at least 2 weeks

You may not qualify if:

• Lack of evidence of INO (slowing of the adducting eye) on physical examination of saccadic speed
• Severe INO (i.e., exotropia in primary gaze) on physical examination
• Medically unstable conditions, inability to give informed consent and understand and cooperate with the testing
• History of side effects from dalfampridine
• History of seizures
• Moderate or severe renal failure, assessed by clearance of creatinine

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• Serra A, Chisari CG, Matta M. Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment. Front Neurol. 2018 Feb 5;9:31. doi: 10.3389/fneur.2018.00031. eCollection 2018.

  PMID: 29467711 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Ocular Motility Disorders; Fatigue

Interventions

4-Aminopyridine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Central Nervous System Diseases; Cranial Nerve Diseases; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Alessandro Serra
• Organization: Louis Stokes VAMC

Alessandro.Serra@va.gov

2167913800

Study Officials

• Alessandro Serra, MD PhD

  Louis Stokes VA Medical Center, Cleveland, OH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2015
• First Posted: March 18, 2015
• Study Start: April 1, 2015
• Primary Completion: January 31, 2019
• Study Completion: March 31, 2019
• Last Updated: September 4, 2020
• Results First Posted: September 4, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)