Assessment of Chronic Guillain-Barre Syndrome Improvement With Use of 4-aminopyridine

Assessment of Chronic GBS Improvement With Use of 4-AP

In developed countries, Guillain-Barre Syndrome (GBS) is the most common cause of acute neuromuscular paralysis, afflicting about 5,000 persons annually in the United States. Over 20% of GBS patients have permanent residual motor deficits that affect their activities of daily living.

The goal of this study is to assess the potential usefulness and safety of 4-aminopyridine (4-AP) in those patients who suffer chronic functional deficits from GBS.This medication is a potassium channel blocker that has the potential to improve nerve conduction, particularly across partially demyelinated axons. It is felt that by increasing nerve conduction there will be improved motor performance for walking and activities of daily living, as well as decreased fatiguability. This medication has demonstrated potential usefulness in central demyelinating diseases such as multiple sclerosis.Because the peripheral nervous system is much more accessible to systemic medication delivery it is felt that this medication may improve the functional status of those patients who are suffering from the residual side effects of this medication.

Study Overview

• Status: Completed
• Conditions: Guillain-Barre Syndrome
• Intervention / Treatment: Drug: 4-aminopyridine (4-AP)

Detailed Description

Objective.- To determine the safety and efficacy of orally delivered 4-aminopyridine for motor weakness due to Guillain-Barre Syndrome (GBS) under a FDA approved protocol (IND No: 58,029).

Setting.- Tertiary care outpatient rehabilitation center directly attached to a university hospital.

Subjects.- Subjects who are unable to ambulate more than 200 feet without assistive devices and have residual nonprogressive motor weakness due to GBS more than one year out from the initial episode.

Design.- Subjects will be randomized to a double-blind, placebo-controlled, cross-over design, which had two eight-week treatment arms with a three-week washout. The average dosage at 4 weeks will be 30 milligrams (mg) per day.

Patients who demonstrate improvement will be continued on the medication for an additional three months. Assessments will be performed every two weeks during the randomized trial and every month for those continued for up to three months on the medication.

• Study Type: Interventional
• Enrollment: 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-2417
      • Rehabilitation Institute of Michigan at Detroit Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Male or Female, 19 to 75 years of age, irrespective of race.
• Subject is able to and has voluntarily given informed consent prior to the performance of any study specific procedures.
• Subject has neurological impairment secondary to GBS, which has been stable for more than 12 months.
• Subject has motor strength that averages less than 5.0 but greater than 3.0 on the ASIA motor scale.
• Subject is able and willing to comply with protocol.
• Subjects will agree to no change in their outpatient therapy, or home exercise programs during enrollment in the study.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
American Spinal Injury Association (ASIA) Motor Score at 8 weeks and 19 weeks
Functional Independence Measure (FIM) Motor scale at 8 weeks and 19 weeks

Secondary Outcome Measures

Outcome Measure
The following are all at 8 weeks and 19 weeks: Hand Dynamometer
Visual Analog Pain Scale
McGill Pain Questionnaire-Short Form
Neuromuscular Functional Assessment Index
Jebsen-Taylor Hand Function Test
Minnesota Rate of Manipulation and Manual Dexterity Tests
The Get Up and Go Test
6-Minute Walk Test
Craig Handicap Assessment and Reporting Technique (CHART
SF-12 Health Survey
Center for Epidemiological Studies Depression Scale (CES-D)
Positive and Negative Affect Schedule (PANAS)

Collaborators and Investigators

• Sponsor: FDA Office of Orphan Products Development

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Study Completion: May 1, 2005

Study Registration Dates

• First Submitted: March 24, 2003
• First Submitted That Met QC Criteria: March 24, 2003
• First Posted (Estimate): March 25, 2003

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: May 1, 2006

More Information

Terms related to this study

• Keywords: Guillain Barre Syndrome; 4-aminopyridine
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyradiculoneuropathy; Polyneuropathies; Syndrome; Guillain-Barre Syndrome; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: 2129