Muscle Cramps in Amyotrophic Lateral SclerosisPhase 4NCT01811355
Mexiletine for the Treatment of Muscle Cramps in ALS
A Phase 4 study testing Mexiletine in people with Muscle Cramps in Amyotrophic Lateral Sclerosis, run by Bjorn Oskarsson, MD at 6 sites in United States.
Trial summary
The purpose of this study is to determine if mexiletine is effective for the treatment of muscle cramps in Amyotrophic Lateral Sclerosis (ALS). Read more about this study
- Who is it for?
- Ages 21 to 89 years
- Conditions the study is for
- Muscle Cramps in Amyotrophic Lateral Sclerosis
- What is being tested?
- Mexiletine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 6 sitesUnited States
- Study dates
- May 2013to May 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- ≥2 cramps per week 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 <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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
UCD Telehealth Network - Lake Almanor Clinic
Chester, California, 96020
UCSD Department of Neurosciences ALS Clinical Trials (ACT) Program
La Jolla, California, 92093
UCLA Neuromuscular Research Program
Los Angeles, California, 90095
UCD Telehealth Network
Multiple Locations, California, Various
UC Irvine Health ALS & Neuromuscular Center
Orange, California, 92868
UC, Davis Medical Center ALS Clinic
Sacramento, California, 95817
About this study
The purpose of this study is to determine if mexiletine is effective for the treatment of muscle cramps in Amyotrophic Lateral Sclerosis (ALS).
Read the 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.
- Being tested
- Mexiletine, Placebo
- Keywords
- Muscle cramps, Cramp, ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig's disease, Motor Neuron Disease, MND
- Medical subject headings
- Muscle Cramp, Amyotrophic Lateral Sclerosis, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MexiletineDrug
Also called Mexetil
Sodium channel blocker
PlaceboDrug
Also called Sugar pill
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Mexiletine | Active comparator | Mexiletine, capsule, 150mg, PO BID, 14 days Receives: Drug: Mexiletine |
| Placebo | Placebo comparator | Placebo, capsule, PO BID, 14 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Daily Muscle Cramps
The average of the daily recording of number of muscle cramps that occurred in the last 24 hours- over a 6 week period.
Measured: 6 weeks
Cramp Severity
Daily cramp severity was rated on the 100-unit visual analog scale. Scores ranged from 0 to 100, with 100 being the greatest amount of cramp severity
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2013 (estimated)
- Study startMay 2013
- Primary completionMar 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Muscle Cramps in Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bjorn Oskarsson, MD
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Davis, ALS Association
- Responsible party
- Sponsor-investigator, Bjorn Oskarsson, MD, University of California, Davis
- Investigators
- Bjorn Oskarsson, MD, Principal investigator, UC Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01811355
- Sponsor's protocol ID
- 378164
- Status last verified
- Jul 2017
- First submitted
- 6 Mar 2013
- Last updated
- 28 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mexiletine for the Treatment of Muscle Cramps in ALS
- ClinicalTrials.gov ID
- NCT01811355
- Acronym / sponsor ID
- 378164
- Keywords
- Muscle cramps, Cramp, ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig's disease, Motor Neuron Disease, MND
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Bjorn Oskarsson, MDUniversity, hospital or other
- Collaborators
- University of California, Davis, ALS Association
- Study start
- May 2013
- Primary completion
- Mar 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 14 Mar 2013 (estimated)
- Results
- Posted 27 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if mexiletine is effective for the treatment of muscle cramps in Amyotrophic Lateral Sclerosis (ALS).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mexiletine | Active comparator | Drug: MexiletineMexiletine, capsule, 150mg, PO BID, 14 days |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, capsule, PO BID, 14 days |
Who may qualify
- Ages
- 21 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
- ≥2 cramps per week during run in week
- Life expectancy > 6 months, estimated by clinician
- Able to take drug capsule by mouth
Key exclusion criteria (18 listed)
- Inability to communicate by telephone or email
- Allergy/ known sensitivity to mexiletine
- Prior use of mexiletine
- AV block unless subject has pacemaker
- Cardiac arrhythmia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MexiletineAlso: MexetilSodium channel blocker | Drug | Mexiletine |
| PlaceboAlso: Sugar pillPlacebo | Drug | Placebo |
Primary outcome
Daily Muscle Cramps
Time frame: 6 weeks
The average of the daily recording of number of muscle cramps that occurred in the last 24 hours- over a 6 week period.
Cramp Severity
Time frame: 6 weeks
Daily cramp severity was rated on the 100-unit visual analog scale. Scores ranged from 0 to 100, with 100 being the greatest amount of cramp severity
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bjorn Oskarsson, MD principal investigator
UC Davis
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mexiletine in people with Muscle Cramps in Amyotrophic Lateral Sclerosis, run by Bjorn Oskarsson, MD at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Daily Muscle Cramps (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2017.