Trial record 3 of 10 for:    Open Studies | "Muscle Cramp"

Mexiletine for the Treatment of Muscle Cramps in ALS

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of California, Davis
Sponsor:
Collaborators:
University of California, Davis
ALS Association
Information provided by (Responsible Party):
Bjorn Oskarsson, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT01811355
First received: March 6, 2013
Last updated: June 22, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to determine if mexiletine is effective for the treatment of muscle cramps in Amyotrophic Lateral Sclerosis (ALS).


Condition Intervention Phase
Muscle Cramps in Amyotrophic Lateral Sclerosis
Drug: Mexiletine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mexiletine for the Treatment of Muscle Cramps in ALS

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Cramp diary [ Time Frame: Daily during the 6 week study ] [ Designated as safety issue: No ]
    Daily recording of number of muscle cramps that occurred in the last 24 hours.


Estimated Enrollment: 30
Study Start Date: May 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Mexiletine
Mexiletine, capsule, 150mg, PO BID, 14 days
Drug: Mexiletine
Other Name: Mexetil
Placebo Comparator: Placebo
Placebo, capsule, PO BID, 14 days
Drug: Placebo
Other Name: Sugar pill

Detailed Description:

Background:

Many ALS patients suffer from painful muscle cramps, but unfortunately we do not have any medication proven to help muscle cramps in ALS. Reducing the pain caused by cramps - which can be debilitating - could help people living with ALS.

Muscle cramps are sudden, painful, and involuntary contractions of a muscle. They are caused by nerve dysfunction. When we examine nerves and muscles electrically, we see cramps as bursts of high-frequency (up to150 Hz) firing of the motor nerve cells. Cramps in ALS are believed to be the result of an increase of persistent sodium currents in the sick lower motor nerve cells.

A medication called Quinine was for many years the commonly used drug for controlling cramps in ALS, but the FDA has advised against its use for cramps because of its potential risks (e.g., death). Today there is no agreement on how to treat cramps in the ALS. The American Academy of Neurology recently encouraged further studies of the treatment of muscle cramps and suggested lidocaine as one of a few drugs of special interest.

Mexiletine:

Mexiletine is a medication closely related to lidocaine that can be taken by mouth (instead of being injected). Mexiletine stops the type of sodium currents that are thought to cause muscle cramps. Mexiletine is a relatively older medication that has been extensively studied in humans. It has been shown to reduce the electrical measures of muscle cramps for other disease conditions. For example, in patients with another severe nerve disease - Machado-Joseph disease (SCA3) - mexiletine treatment led to a decrease in the average number of muscle cramps from 24 to 3 cramps per month.. The safety profile of mexiletine is good, with the most frequent side effects being nausea or other abdominal symptoms. These side effects are rare at the doses (300 mg/day) used in this study. In patients with normal heart function, mexiletine has a minimal effect on heart rhythm. In previous clinical trials, no subject developed any serious heart rate problem.

Experimental Plan:

Using multiple sites within the State of California we will quickly enroll a small number (N=30) of ALS patients with severe muscle cramps. The study is a double-blinded, placebo controlled (i.e., the investigator and the participant does not know if the pills contain mexiletine or placebo), crossover (all subjects receive two weeks of mexiletine and two weeks of placebo) study.

After a one week run in, participants will be evaluated on their ability to fill out the cramp diary. Participants who filled out their diary will be randomly assigned to either mexiletine or placebo for their first two weeks. For the first three days of each 2-week period, one 150mg capsule will be taken at bed time. For day 4 to 14 one capsule twice per day will be taken. Each treatment period will be 2 weeks with an intervening 1 week washout period - for a total study length of 6 weeks. Safety will be monitored with liver function studies and EKG's.

  Eligibility

Ages Eligible for Study:   21 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ALS diagnosed according to El Escorial criteria (Awaji version) as: Possible, Probable, or Definite.
  • Experiencing cramps as a moderate or severe symptom as defined by willingness to take a medication for the symptom
  • ≥4 cramps per day on average during run in week
  • Life expectancy > 6 months, estimated by clinician
  • Able to take drug capsule by mouth
  • No significant EKG abnormality on screening
  • aspartate aminotransferase / alanine aminotransferase / alkaline phosphatase <2x upper limit of normal measured at screening
  • Having successfully filled out the cramp diary and cramp and fasciculation scales on six out of the last seven days of run in period

Exclusion Criteria:

  • Inability to communicate by telephone or email
  • Allergy/ known sensitivity to mexiletine
  • Prior use of mexiletine
  • AV block unless subject has pacemaker
  • Cardiac arrhythmia
  • Prior myocardial infarction
  • Other significant EKG abnormality
  • Liver disease
  • History of leucopenia (WBC <3,500/mm3)
  • Epilepsy
  • Other serious and unstable medical condition
  • Pregnant woman
  • Breastfeeding woman
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Use of quinidine (alone or as a component of Nuedexta®) during the study
  • Inability or unwillingness of subject to give written informed consent
  • Woman of childbearing potential, not willing to use at least two approved methods of contraception
  • Use of a prohibited medication during study
  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: NCT01811355

Contacts
Contact: Bjorn Oskarsson, MD 916 734 4660 bjorn.oskarsson@ucdmc.ucdavis.edu
Contact: Michelle Cregan (916) 734-6304 michelle.cregan@ucdmc.ucdavis.edu

Locations
United States, California
UCD Telehealth Network - Lake Almanor Clinic Enrolling by invitation
Chester, California, United States, 96020
UCSD Department of Neurosciences ALS Clinical Trials (ACT) Program Not yet recruiting
La Jolla, California, United States, 92093
Contact: Ivy Chippendale    858-246-0247    ichippendale@ucsd.edu   
Contact: Aaryn Belfer    858-246-0247    abelfer@ucsd.edu   
Principal Investigator: John Ravits, MD         
UCLA Neuromuscular Research Program Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Rebecca Alvarez    310-825-5232    rralvarez@mednet.ucla.edu   
Principal Investigator: Martina Wiedau-Pazos, MD         
UCD Telehealth Network Recruiting
One hundred sites, California, United States, Various
Contact: Bjorn Oskarsson, MD    9167346304    bjorn.oskarsson@ucdmc.ucdavis.edu   
Contact: Michelle Cregan Oskarsson, MD    9167346304    michelle.cregan@ucdmc.ucdavis.edu   
Principal Investigator: Bjorn Oskarsson, MD         
UC Irvine Health ALS & Neuromuscular Center Not yet recruiting
Orange, California, United States, 92868
Contact: Brian Minton    714-456-8520    bminton@uci.edu   
Contact: Veronica Martin    7144562332    vero@uci.edu   
Principal Investigator: Tahseen Mozaffar, MBBS         
UC, Davis Medical Center ALS Clinic Recruiting
Sacramento, California, United States, 95817
Contact: Bjorn Oskarsson, MD       bjorn.oskarsson@ucdmc.ucdavis.edu   
Principal Investigator: Bjorn Oskarsson, MD         
Sponsors and Collaborators
Bjorn Oskarsson, MD
University of California, Davis
ALS Association
Investigators
Principal Investigator: Bjorn Oskarsson, MD UC Davis
  More Information

Additional Information:
No publications provided

Responsible Party: Bjorn Oskarsson, MD, Assistant Professor of Clinical Neurology, University of California, Davis
ClinicalTrials.gov Identifier: NCT01811355     History of Changes
Other Study ID Numbers: 378164-3
Study First Received: March 6, 2013
Last Updated: June 22, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of California, Davis:
Muscle cramps
Cramp
ALS
Amyotrophic Lateral Sclerosis
Lou Gehrig's disease
Motor Neuron Disease
MND

Additional relevant MeSH terms:
Muscle Cramp
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms
Pathologic Processes
Mexiletine
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014