Clinical trial: Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (NCT02781454)

Eligibility criteria:
Inclusion Criteria:

          1. Sporadic ALS diagnosed as possible, laboratory-supported probable, probable, or
             definite ALS as defined by revised El Escorial criteria.

          2. Age 18 years or older.

          3. Symptom onset of weakness or spasticity due to ALS ≤ 60 months prior to Screening
             Visit.

          4. Slow vital capacity (SVC) measure ≥50% of predicted for gender, height, and age at the
             screening visit.

          5. Must be able to swallow capsules throughout the course of the study, according to Site
             Investigator judgment.

          6. Capable of providing informed consent and following trial procedures.

          7. For TMS: a resting motor threshold defined as 50% of pulses eliciting a motor evoked
             potential (MEP) of amplitude ≥ 50 µV.

          8. For TTNCS: median Compound Muscle Action Potential (CMAP) ≥ 1.5 mV.

          9. Subjects must not have taken riluzole for at least 30 days or be on a stable dose of
             riluzole for at least 30 days prior to the Screening Visit and continue on the stable
             dose throughout the course of the study (riluzole-naïve subjects are permitted in the
             study).

         10. Subjects must not have taken medication for muscle cramping such as cyclobenzaprine,
             baclofen, carisoprodol, or methocarbamol, for at least 30 days prior to screening or
             be on a stable dose for at least 60 days prior to screening.

         11. Geographic accessibility to the site.

         12. 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.

         13. Use of medications known to affect the neurophysiology measures in the study must be
             scheduled, not as needed (pro re nata, PRN). A subject must have been on a fixed dose
             for 30 days prior to the Screening Visit, and there must be no reason to believe that
             a subsequent change would be necessary during the course of the study. These
             medications include: benzodiazepines, muscle relaxants, tricyclic antidepressants,
             selective serotonin reuptake inhibitors, non-selective serotonin reuptake inhibitors,
             hypnotics (including anti-histamines) and anti-cholinergics.

        Exclusion Criteria:

          1. Invasive ventilator dependence, such as tracheostomy.

          2. Creatinine level greater than 1.5 mg/dL at screening.

          3. Serum Glutamic-Oxaloacetic (SGOT/AST) / Serum Glutamic-Pyruvic (SGPT/ALT) greater than
             3 times the upper limit of normal at screening.

          4. History of known sensitivity or intolerability to mexiletine or lidocaine.

          5. Any history of either substance abuse within the past year, unstable psychiatric
             disease, cognitive impairment, or dementia.

          6. Clinically significant conduction abnormalities on electrocardiogram or a known
             history of cardiac arrhythmia.

          7. Known history of epilepsy.

          8. Known history of congestive heart failure (CHF) or history of myocardial infarction
             within the past 24 months.

          9. Use of mexiletine for 30 days prior to Screening Visit.

         10. Exposure to any other experimental agent (off-label use or investigational) including
             high dose creatine (>10 grams a day) within 30 days prior to Screening Visit.

         11. Metal in the head and neck region, cardiac pacemaker or brain stimulator, cochlear
             implants, implanted infusion device or personal history of epilepsy.

         12. Use of amiodarone, flecainide, duloxetine, tizanidine, or clozapine.

         13. Pregnant women or women currently breastfeeding.

         14. Placement of Diaphragm Pacing System (DPS) device < 60 days prior to Screening Visit.

         15. Planned DPS device implantation during study participation
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient description (patient's own words): I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Does the patient match the trial criteria? Entailment