Controlled Trial of 3,4-Diaminopyridine (3-4DAP) in Lambert-Eaton Myasthenic Syndrome (LEMS)

Phase 2

Terminated

• Conditions: Muscle Weakness
• Interventions: Drug: 3-4 Diaminopyridine

• Registration Number: NCT02090725
• Lead Sponsor: Jeffrey A. Cohen, MD

Brief Summary

The main purpose for this study is to provide access to 3,4 DAP, a drug which has demonstrated to be effective in treating weakness associated with Lambert-Eaton Myasthenic Syndrome. LEMS is a rare autoimmune cause of a defect in neuromuscular transmission. The disorder is clinically characterized by fluctuating muscle weakness, hyporeflexia and autonomic dysfunction.

Detailed Description

More than half of LEMS cases are associated with malignancy, usually small cell lung cancer. These paraneoplastic cases progress more quickly than primary autoimmune LEMS. An overlap syndrome with other autoimmune diseases is often detected in LEMS patients.

3,4 DAP is effective in LEMS because it increases calcium influx into the nerve terminal by blocking potassium efflux and thereby prolonging the presynaptic action potential. 3,4 DAP is less likely to provoke epileptic seizures than its precursor, 4-aminopyridine, because it is less able to cross the blood-brain barrier. 3,4 DAP is effective in increasing strength and improving autonomic symptoms in LEMS patients of both the primary autoimmune and paraneoplastic etiologies.

Study Timeline

• Study Start: 2004-02
• Study First Submitted: 2014-03-14
• Study First Submitted QC: 2014-03-14
• Study First Posted: 2014-03-18
• Primary Completion: 2018-07
• Study Completion: 2018-11-28
• Results First Submitted: 2019-03-26
• Status Verified: 2019-05
• Results First Submitted QC: 2019-05-01
• Last Update Submitted: 2019-05-01
• Results First Posted: 2019-05-21
• Last Update Posted: 2019-05-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

-Male or female majority between 45 and 60 years of age

• diagnosed with Lambert-Eaton Myasthenic Syndrome.
• subjects must be taking full dose of pyridostigmine

Exclusion Criteria

• does subject have a history of liver problems?

• does subject have a history of prolonged QTc syndrome (which is a condition where there is prolongation between the start of the Q wave and the end of the T wave in the heart's electrical cycle).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
3-4 Diaminopyridine (DAP)	3-4 Diaminopyridine	-

Primary Outcome Measures

Name	Time	Method
Number of Participants That Showed Improvement in Muscle Weakness During Their Last Study Related Visit	Participants were followed until they withdrew or the study ended. Time frame ranged from 1 month to 3 years.	Muscle weakness will be assessed monthly for the first 3 months based on clinical assessment during office visits. Muscle weakness will then be assessed every 6 months once the patient is stabilized based on clinical assessments during office visits. The assessment of whether there was an improvement in muscle weakness, based on the PI's clinical judgment, was noted during the last study visit completed by the participant.

Trial Locations

Locations (1)

Dartmouth-Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States