Clinical trial NCT02251457: Study of Ranolazine in Myotonia Congenita, Paramyotonia Congenita and Myotonic Dystrophy Type 1
Official title: Open Label Trial of Ranolazine in Myotonia Congenita, Paramyotonia Congenita, & Myotonic Dystrophy Type 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myotonia Congenita
Paramyotonia Congenita
Myotonic Dystrophy 1
Keywords: Myotonia Congenita
ranolazine
Ohio State
Open Label
Paramyotonia Congenita
Myotonic Dystrophy 1
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2014-09-29
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to gather preliminary data to determine if ranolazine is a safe and effective treatment for the symptoms of myotonia congenital, paramyotonia congenita, and myotonic dystrophy type 1. The duration of the study is 5 weeks.

Detailed description: Recent advances in the understanding of myotonia congenita have identified potential areas that could possibly respond to treatment in a drug study. The drug ranolazine (trade name Ranexa) is a FDA-approved medication to treat chest pain in patients with heart disease. Ranolazine has been studied in mice with myotonia congenita. The data from this animal model suggest that ranolazine may improve the symptoms and signs of myotonia. All individuals that participate will be placed on active drug. The investigators want to see if this drug is safe to take without causing too many side effects for people with myotonia congenita, paramyotonia congenital and myotonic dystrophy type 1. Participants will go to The Ohio State University for study visits. Participants will take ranolazine for four weeks. Participants can expect a total of 4 study visits and 2 phone calls over the 5 week period.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of myotonia congenital, paramyotonia congenital or Myotonic Dystrophy Type 1 established by genetic testing in the subject or in a first-degree relative.
* Clinically evident myotonia

Exclusion Criteria:

* Contraindications to ranolazine use:

  * for fungus infection: ketoconazole (Nizoral), itraconazole (Sporanox, Onmel)
  * for infection: clarithromycin (Biaxin)
  * for depression: nefazodone
  * for HIV: nelfinavir (Viracept), ritonavir (Norvir), lopinavir and ritonavir (Kaletra), indinavir (Crixivan), saquinavir (Invirase).
  * for tuberculosis (TB): rifampin (Rifadin), rifabutin (Mycobutin), rifapentine (Priftin)
  * for seizures: phenobarbital, phenytoin (Phenytek, Dilantin, Dilantin-125), carbamazepine (Tegretol)
  * the herbal supplement St. John's wort

    * you have scarring (cirrhosis) of your liver
* Concurrent use of mexiletine, lacosamide, acetazolamide, phenytoin, quinine, procainamide, Saint John wort or tocainide. Patients who were previously treated with these medications may participate. They need to be off of the medication for at least a week prior to enrollment.
* QTc \>470 ms for men and \>480 ms for women.
* Women who are pregnant or breastfeeding
* Direct family history of sudden cardiac death

Primary outcomes:
measure: Questionnaires: Short Form Health Survey (SF-36) and Individualized Neuromuscular Quality of Life Questionnaire (INQoL)
timeFrame: 1 month
measure: Muscle tasks
timeFrame: 1 month
measure: Electromyography (EMG) Myotonia
timeFrame: 1 month
Secondary outcomes:
measure: Electrocardiogram (ECG)
timeFrame: 1 month
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: William D Arnold, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Novak KR, Norman J, Mitchell JR, Pinter MJ, Rich MM. Sodium channel slow inactivation as a therapeutic target for myotonia congenita. Ann Neurol. 2015 Feb;77(2):320-32. doi: 10.1002/ana.24331. Epub 2015 Jan 9.
citation: Lorusso S, Kline D, Bartlett A, Freimer M, Agriesti J, Hawash AA, Rich MM, Kissel JT, David Arnold W. Open-label trial of ranolazine for the treatment of paramyotonia congenita. Muscle Nerve. 2019 Feb;59(2):240-243. doi: 10.1002/mus.26372. Epub 2018 Dec 21.