Sporadic Amyotrophic Lateral SclerosisPhase 2MX-ALS-001NCT01849770
Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (SALS)
A Phase 2 study testing Mexiletine in people with Sporadic Amyotrophic Lateral Sclerosis, run by University of Washington at 10 sites in United States.
Trial summary
The purpose of this research is to find out if mexiletine is safe and effective in people with Amyotrophic Lateral Sclerosis (ALS). In this trial, participants will be taking either 300 milligrams per day of mexiletine, 900 milligrams per day of mexiletine or placebo (non-active study drug). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sporadic 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
- 75 participants
- Where
- 10 sitesUnited States
- Study dates
- Jul 2013to Aug 2014
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sporadic Amyotrophic Lateral Sclerosis (SALS) diagnosed as possible, laboratory-supported probable, probable, or definite ALS as defined by revised El Escorial criteria.
- Age 18 years or older.
- Disease duration ≤ 36 months from ALS symptom onset.
- Capable of providing informed consent and following trial procedures.
- Subjects must not have taken riluzole for at least 30 days or be on a 50 milligrams twice daily dose of riluzole for at least 60 days prior to randomization (riluzole-naïve subjects are permitted in the study).
- Subjects must not have taken medication for muscle cramping such as cyclobenzaprine, baclofen, carisoprodol, or methocarbamol, for at least 30 days prior to randomization or be on a stable dose for at least 60 days prior to randomization.
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- Geographic accessibility to the site.
- Women must not become pregnant for the duration of the study and must be willing to use two contraceptive therapies and have a negative pregnancy test throughout the course of the study.
- Slow vital capacity (SVC) measure greater than or equal to 50% of predicted for gender, height, and age at the screening visit.
- Subjects medically able to undergo lumbar puncture (LP) as determined by the investigator (for example, no bleeding disorder, allergy to local anesthetics, a skin infection at or near the LP site, or evidence of high intracranial pressure).
- Must be able to swallow capsules throughout the course of the study, according to Principal Investigator (PI) judgment.
- Must have a caregiver assist with dispensing the study drug.
Who cannot join
- Invasive ventilator dependence, such as tracheostomy.
- Creatinine level greater than 1.5 milligram/deciliter.
- Serum glutamic oxaloacetic transaminase or (aspartate transaminase) / serum glutamic pyruvic transaminase (alanine aminotransferase) greater than 3 times the upper limit of normal at screening.
- History of known sensitivity or intolerability to mexiletine or lidocaine.
- Any history of either substance abuse within the past year, unstable psychiatric disease, cognitive impairment, or dementia.
- Clinically significant conduction abnormalities on electrocardiogram or a known history of cardiac arrhythmia.
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- Known history of epilepsy.
- Known history of congestive heart failure (CHF) or history of myocardial infarction within the past 24 months.
- Use of mexiletine for 60 days prior to Baseline Visit.
- Exposure to any other experimental agent (off-label use or investigational) including high dose creatine (greater than 10 grams a day) within 30 days prior to Baseline Visit.
- Use of amiodarone, flecainide, duloxetine, tizanidine, or clozapine.
- Pregnant women or women currently breastfeeding.
- Placement of Diaphragm Pacing System (DPS) device less than 60 days prior to Baseline Visit.
- Planned DPS device implantation after Baseline Visit.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390-8897
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Iowa
Iowa City, Iowa, 52242
University of Kansas Medical Center
Kansas City, Kansas, 66160
UCLA, Neuromuscular Research Center
Los Angeles, California, 90095
University of Washington Medical Center
Seattle, Washington, 98195
Washington University Medical School
St Louis, Missouri, 63110
SUNY Upstate Medical Center
Syracuse, New York, 13210
University of Massachusetts (Worcester) Memorial Medical Center
Worcester, Massachusetts, 01655
About this study
Official title: A Safety and Tolerability Study of Mexiletine in Patients With Sporadic Amyotrophic Lateral Sclerosis (SALS)
The purpose of this research is to find out if mexiletine is safe and effective in people with Amyotrophic Lateral Sclerosis (ALS). In this trial, participants will be taking either 300 milligrams per day of mexiletine, 900 milligrams per day of mexiletine or placebo (non-active study drug). The safety and efficacy of these doses will be compared to see if one dose is better than the other.
Read the detailed description
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting primarily motor neurons, for which treatment designed to slow or arrest progression remains lacking. Mexiletine is a use-dependent sodium channel blocker that has been FDA-approved for decades for the treatment of cardiac arrhythmias and more recently to treat neuropathic pain in diabetic polyneuropathy. Mexiletine has been shown also to be protective of neurons following spinal cord, head injury, and cerebral ischemia, largely by blocking excitotoxicity. Based on previous studies, mexiletine appears to penetrate into the central nervous system at concentrations sufficient to confer significant protection. Recent unpublished studies in the laboratory of Dr. Robert Brown at the University of Massachusetts have also demonstrated that mexiletine ingestion in mice genetically engineered to express high levels of mutant cytosolic copper-zinc superoxide dismutase-1 (SOD1) transgene prolongs survival in these animals. As mexiletine already has FDA-approval as an anti-arrhythmic agent, much is known about the pharmacology and safety of this drug in non-ALS patients. We anticipate that by excluding subjects with a known history of cardiac disease and with the known neuroprotectant properties of this medication, mexiletine is a good choice for further study in an ALS clinical trial.
- Conditions
- Sporadic Amyotrophic Lateral Sclerosis
- Being tested
- Mexiletine, Placebo
- Keywords
- SALS, Mexiletine, Safety
- Medical subject headings
- Amyotrophic lateral sclerosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MexiletineDrug
Also called Mexitil
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Mexiletine, 300 milligrams | Active comparator | Mexiletine, 300 milligrams by mouth per day for 12 weeks. Receives: Drug: Mexiletine |
| Mexiletine, 900 milligrams | Active comparator | Mexiletine, 900 milligrams by mouth per day for 12 weeks. Receives: Drug: Mexiletine |
| Placebo | Placebo comparator | Placebo, by mouth per day for 12 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants That Discontinued Study Drug
Information on adverse effects of mexiletine will be determined at each visit by direct questioning of the subjects, clinical examination, review of concomitant medications, vital signs and laboratory test results.
Measured: Screening, Baseline Visit Pre-Dose and Post-Dose, Weeks 2, 6, and 12, and at the Final Safety Visit, if a subject discontinues study drug early. Adverse Events will be assessed via telephone Weeks 1, 10, and 16.
Secondary outcomes (10)
Trough Plasma Concentration (Cmin) of Mexiletine
Subjects will have blood drawn to assess mexiletine concentrations for pharmacokinetics (PK) at the Week 6 Visit.
Measured: Week 6 Visit (pre-dose, hours 1, 2, 3, and 6 post-dose on Week 6)
Peak Plasma Concentration (Cmax) of Mexiletine
Subjects will have blood drawn to assess mexiletine concentrations for pharmacokinetics (PK) at the Week 6 Visit.
Measured: Week 6 Visit (pre-dose, hours 1, 2, 3, and 6 post-dose on Week 6)
Area Under the Concentration Time Curve (AUC) of Mexiletine in Plasma.
Subjects will have blood drawn to assess mexiletine concentrations for pharmacokinetics (PK) at the Week 6 Visit.
Measured: Week 6 Visit (up to 6 hours post dose)
Mean Cerebrospinal Fluid (CSF)/Plasma Ratio
The concentrations of Mexiletine were measured in cerebrospinal fluid (CSF) and plasma.
Measured: Week 6 Visit (up to 6 hours post dose)
Mean Weekly Cramp Frequency
Measured: Week 3-12, post titration of study medication
Maximal Pain Severity
At the Baseline Visit, subjects will be asked to recount the maximum intensity experienced with a muscle cramp in the previous 24 hours and the maximum intensity experienced with a muscle cramp in the previous 30 days.
The visual analog scale (VAS) will be used to measures pain associated with muscle cramping. It will be used to measure muscle cramp intensity in this study. The scale rating is from 0-10; 0 equals no symptoms, 10 equals most severe symptoms.
Subject will be provided with a muscle cramp diary to record muscle cramp intensity at home, daily.
Measured: Weeks 3-12, post titration of study medication
Cramp Frequency - Ratios for Comparisons of Doses for Weeks 3-12
Measured: Week 3-12, post titration of study medication
Maximal Pain Severity - Ratios for Comparisons of Doses for Weeks 3-12
Measured: Week 3-12, post titration of study medication
Mean Pain Severity
At the Baseline Visit, subjects will be asked to recount the maximum intensity experienced with a muscle cramp in the previous 24 hours and the maximum intensity experienced with a muscle cramp in the previous 30 days.
The visual analog scale (VAS) will be used to measures pain associated with muscle cramping. It will be used to measure muscle cramp intensity in this study. The scale rating is from 0-10; 0 equals no symptoms, 10 equals most severe symptoms.
Subject will be provided with a muscle cramp diary to record muscle cramp intensity at home, daily.
Measured: Weeks 3-12, post titration of study medication
Mean Pain Severity - Ratios for Comparisons of Doses for Weeks 3-12
Measured: Week 3-12, post titration of study medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2013 (estimated)
- Study startJul 2013
- Primary completionAug 2014
- Study completionAug 2014
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 Sporadic Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael D Weiss, University of Washington
- Investigators
- Michael D Weiss, MD, Principal investigator, University of Washington Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01849770
- Sponsor's protocol ID
- 43708
- Acronym
- MX-ALS-001
- Status last verified
- Sep 2021
- First submitted
- 6 May 2013
- Last updated
- 29 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Tolerability Study of Mexiletine in Patients With Sporadic Amyotrophic Lateral Sclerosis (SALS)
- ClinicalTrials.gov ID
- NCT01849770
- Acronym / sponsor ID
- MX-ALS-001 / 43708
- Conditions
- Sporadic Amyotrophic Lateral Sclerosis
- Keywords
- SALS, Mexiletine, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 8 May 2013 (estimated)
- Results
- Posted 12 Oct 2015
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 research is to find out if mexiletine is safe and effective in people with Amyotrophic Lateral Sclerosis (ALS). In this trial, participants will be taking either 300 milligrams per day of mexiletine, 900 milligrams per day of mexiletine or placebo (non-active study drug). The safety and efficacy of these doses will be compared to see if one dose is better than the other.
Detailed description
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting primarily motor neurons, for which treatment designed to slow or arrest progression remains lacking. Mexiletine is a use-dependent sodium channel blocker that has been FDA-approved for decades for the treatment of cardiac arrhythmias and more recently to treat neuropathic pain in diabetic polyneuropathy. Mexiletine has been shown also to be protective of neurons following spinal cord, head injury, and cerebral ischemia, largely by blocking excitotoxicity. Based on previous studies, mexiletine appears to penetrate into the central nervous system at concentrations sufficient to confer significant protection. Recent unpublished studies in the laboratory of Dr. Robert Brown at the University of Massachusetts have also demonstrated that mexiletine ingestion in mice genetically engineered to express high levels of mutant cytosolic copper-zinc superoxide dismutase-1 (SOD1) transgene prolongs survival in these animals. As mexiletine already has FDA-approval as an anti-arrhythmic agent, much is known about the pharmacology and safety of this drug in non-ALS patients. We anticipate that by excluding subjects with a known history of cardiac disease and with the known neuroprotectant properties of this medication, mexiletine is a good choice for further study in an ALS clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Mexiletine, 300 milligrams | Active comparator | Drug: MexiletineMexiletine, 300 milligrams by mouth per day for 12 weeks. |
| Mexiletine, 900 milligrams | Active comparator | Drug: MexiletineMexiletine, 900 milligrams by mouth per day for 12 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, by mouth per day for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Sporadic Amyotrophic Lateral Sclerosis (SALS) diagnosed as possible, laboratory-supported probable, probable, or definite ALS as defined by revised El Escorial criteria.
- Age 18 years or older.
- Disease duration ≤ 36 months from ALS symptom onset.
- Capable of providing informed consent and following trial procedures.
- Subjects must not have taken riluzole for at least 30 days or be on a 50 milligrams twice daily dose of riluzole for at least 60 days prior to randomization (riluzole-naïve subjects are permitted in the study).
Key exclusion criteria (14 listed)
- Invasive ventilator dependence, such as tracheostomy.
- Creatinine level greater than 1.5 milligram/deciliter.
- Serum glutamic oxaloacetic transaminase or (aspartate transaminase) / serum glutamic pyruvic transaminase (alanine aminotransferase) greater than 3 times the upper limit of normal at screening.
- History of known sensitivity or intolerability to mexiletine or lidocaine.
- Any history of either substance abuse within the past year, unstable psychiatric disease, cognitive impairment, or dementia.
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: Mexitil | Drug | Mexiletine, 300 milligrams, Mexiletine, 900 milligrams |
| Placebo | Drug | Placebo |
Primary outcome
Percentage of Participants That Discontinued Study Drug
Time frame: Screening, Baseline Visit Pre-Dose and Post-Dose, Weeks 2, 6, and 12, and at the Final Safety Visit, if a subject discontinues study drug early. Adverse Events will be assessed via telephone Weeks 1, 10, and 16.
Information on adverse effects of mexiletine will be determined at each visit by direct questioning of the subjects, clinical examination, review of concomitant medications, vital signs and laboratory test results.
10 secondary outcomes
Trough Plasma Concentration (Cmin) of Mexiletine
Time frame: Week 6 Visit (pre-dose, hours 1, 2, 3, and 6 post-dose on Week 6)
Peak Plasma Concentration (Cmax) of Mexiletine
Time frame: Week 6 Visit (pre-dose, hours 1, 2, 3, and 6 post-dose on Week 6)
Area Under the Concentration Time Curve (AUC) of Mexiletine in Plasma.
Time frame: Week 6 Visit (up to 6 hours post dose)
Mean Cerebrospinal Fluid (CSF)/Plasma Ratio
Time frame: Week 6 Visit (up to 6 hours post dose)
Mean Weekly Cramp Frequency
Time frame: Week 3-12, post titration of study medication
Maximal Pain Severity
Time frame: Weeks 3-12, post titration of study medication
Cramp Frequency - Ratios for Comparisons of Doses for Weeks 3-12
Time frame: Week 3-12, post titration of study medication
Maximal Pain Severity - Ratios for Comparisons of Doses for Weeks 3-12
Time frame: Week 3-12, post titration of study medication
Mean Pain Severity
Time frame: Weeks 3-12, post titration of study medication
Mean Pain Severity - Ratios for Comparisons of Doses for Weeks 3-12
Time frame: Week 3-12, post titration of study medication
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Northeast ALS Consortium WebsiteLink provided by the sponsor.
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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.
Michael D Weiss, MD principal investigator
University of Washington Medical School
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mexiletine in people with Sporadic Amyotrophic Lateral Sclerosis, run by University of Washington at 10 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 12 inclusion and 14 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 29 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 12 Oct 2015). 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?
Percentage of Participants That Discontinued Study Drug (time frame: Screening, Baseline Visit Pre-Dose and Post-Dose, Weeks 2, 6, and 12, and at the Final Safety Visit, if a subject discontinues study drug early. Adverse Events will be assessed via telephone Weeks 1, 10, and 16.). 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 29 Sep 2021.