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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Jacobus Pharmaceutical
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT02090725
First received: March 14, 2014
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Muscle Weakness
Drug: 3-4 Diaminopyridine

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Controlled Trial of 3,4-Diaminopyridine in LEMS

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Change in muscle weakness [ Time Frame: Month 1, Month 2, Month 3, then changing to every 6 months once patient is stable ] [ Designated as safety issue: Yes ]
    Muscle weakness will be assessed monthly for the first 3 months based on office visits and blood tests (complete blood count (CBC), electrolytes, glucose, liver function tests, blood urea nitrogen (BUN), creatinine). Muscle weakness will then be assessed every 6 months once the patient is stabilized based on office visits and blood tests (CBC, electrolytes, glucose, liver function tests, BUN, creatinine).


Enrollment: 3
Study Start Date: February 2004
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 3-4 Diaminopyridine (DAP) Drug: 3-4 Diaminopyridine
Other Name: 3-4 DAP

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.

  Eligibility

Ages Eligible for Study:   45 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  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: NCT02090725

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03221
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Jacobus Pharmaceutical
Investigators
Principal Investigator: Jeffrey A. Cohen, MD Dartmouth-Hitchcock Medical Center
  More Information

No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT02090725     History of Changes
Other Study ID Numbers: 16767
Study First Received: March 14, 2014
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:
fluctuating muscle weakness
hyporeflexia
autonomic Dysfunction

Additional relevant MeSH terms:
Lambert-Eaton Myasthenic Syndrome
Paraneoplastic Syndromes, Nervous System
Paraneoplastic Syndromes
Asthenia
Muscle Weakness
Paresis
Signs and Symptoms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Pathologic Processes
3,4-diaminopyridine
4-Aminopyridine
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014