Combining N-of-1 trials to estimate population clinical effectiveness of drugs using Bayesian hierarchical modeling. The case of Mexilitin for patients with Non-Dystrophic Myotonia. - Mex vs. placebo in NDMs

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2010-024026-38-NL
• Date of registration: 09/02/2011
• Prospective Registration: Yes
• Primary sponsor: Radboud University Nijmegen Medical Center
• Public title: Combining N-of-1 trials to estimate population clinical effectiveness of drugs using Bayesian hierarchical modeling. The case of Mexilitin for patients with Non-Dystrophic Myotonia. - Mex vs. placebo in NDMs
• Scientific title: Combining N-of-1 trials to estimate population clinical effectiveness of drugs using Bayesian hierarchical modeling. The case of Mexilitin for patients with Non-Dystrophic Myotonia. - Mex vs. placebo in NDMs
• Date of first enrolment: 10/01/2012
• Target sample size: 30
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024026-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: yes Other: yes Other trial design description: combined N-of-1 trials If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
1. At least 18 years of age
2. Genetically confirmed diagnosis of NDMs
3. Participation in the “Genetical variability of the Non-dystrophic Myotonia” study of J. Trip or a new patient with genetically confirmed NDM.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Inability or unwillingness to provide informed consent.

2. Other neurological conditions that might affect the assessment of the study
measurements.

3. Genetic confirmed DM1 (CTG > 50 repeats), or DM2.

4. Patients with existing cardiac conduction defects, evidenced on ECG including but
not limited to the following conditions: malignant arrhythmia or cardiac conduction
disturbances (such as second degree AV block, third degree AV block, or prolonged
QT interval >500 ms or QRS duration > 150 msec).

5. Current use of the following antiarrhythmic medication for a cardiac disorder:
flecainide acetate, encainide, disopyramide, procainamide, quinidine, propafenone
or mexiletine.

6. Women who are pregnant or lactating.

7. Patients currently on medications for myotonia such as phenytoin and flecainide
acetate within 5 days of enrollment, carbamazepine and mexiletine within 3 days of
enrollment, or propafenone, procainamide, disopyramide, quinidine and encainide
within 2 days of enrollment.

8. Patients with an existing permanent pacemaker.

9. Patients with renal or hepatic disease, heart failure, or seizure disorders.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with non-dystrophic myotonic syndromes (NDMs). NDMs are caused by mutations in the gene encoding for the skeletal muscle sodium (SCN4A) or chloride (CLCN1) channel. In this study patients with NDMs with a genetically confirmed mutation in the SCN4A-gene or the CLCN1-gene as registred in the Netherlands database of NDMs will be included.

Intervention(s)

Trade Name: Mexitil
Product Name: mexitil
Pharmaceutical Form: Tablet
INN or Proposed INN: MEXILETINE
CAS Number: 31828714
Current Sponsor code: -
Other descriptive name: Mexitil
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600 -
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The objective of this project is to further refine N-of-1 trial methodology, and explore whether Bayesian analysis of multiple N-of-1 trials can serve as a sufficient basis for coverage decisions on drugs for rare diseases.

Primary end point(s): Because of the N-of-1 trials design primary end points will be evaluated by the trial statistician after each treatment pair.

Secondary Objective: The previously mentioned will be tested in combined N-of-1 trials using mexiletine vs. placebo in NDM patients. The secondary objective of this proposal is to assess whether mexiletine improves myotonia measured (both quantitatively and qualitative) in patients with non-dystrophic myotonia.

Secondary ID(s)

mex201011