MExiletine Versus Lamotrigine in Non-Dystrophic Myotonias
MEND
A Phase III, Randomised, Double Blinded, Head-to-head, Single-site, Cross-over Trial of Lamotrigine Versus Mexiletine for Non-dystrophic Myotonias
1 other identifier
interventional
60
1 country
1
Brief Summary
This is a clinical trial to determine if Lamotrigine is non-inferior to Mexiletine for the treatment of myotonia in patients with Non-Dystrophic Myotonia. Non-dystrophic Myotonia is a genetic condition for which there is no cure. It affects patients for the duration of their life and impacts work, leisure and can lead to significant morbidity. The study is a cross-over design - participants will be randomized to either lamotrigine or mexiletine first for 8 weeks and then swap over after a week wash-out to the other medication for a further 8 weeks. Participants and investigators will be blinded to the treatment schedule. 60 participants will recruited through the clinical service, national registry and national liaison.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Aug 2021
Typical duration for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 11, 2021
CompletedStudy Start
First participant enrolled
August 12, 2021
CompletedFirst Posted
Study publicly available on registry
August 23, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
April 2, 2024
CompletedNovember 2, 2022
November 1, 2022
2 years
August 11, 2021
November 1, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Interactive Voice Response (IVR) -diary score
Improvement seen on the 9 point Interactive Voice Response (IVR) -diary score
Time Frame: last two weeks of each treatment period - [Minimum value 0- no myotonia. Maximum value 9 - severe myotonia].
Secondary Outcomes (6)
Secondary Outcome - Timed up and go
end of each treatment period (two months)
Secondary Outcome - Timed sit to stand
end of each treatment period (two months)
Fatigue Scale
end of each treatment period (two months)
Secondary Outcome
end of each treatment period (two months)
Short-Form Health Survey (SF-36)
end of each treatment period (two months)
- +1 more secondary outcomes
Study Arms (2)
Lamotrigine
ACTIVE COMPARATORWhen on the lamotrigine treatment arm, the participant will commence at lamotrigine 25mg (milligram) daily for two weeks; then increase to 25mg twice daily for two weeks; then increase to 50mg daily for one week; then increase to 100mg in the morning, 50mg at midday and 50mg at night for one week; then increase to 100mg in the morning, 50mg at midday and 100mg at night for two weeks.
Mexiletine
ACTIVE COMPARATORWhen on the mexiletine treatment arm, the participant will commence at mexiletine 100mg daily for two weeks; then increase to 200mg daily for two weeks; then increase to 200mg twice daily for one week; then increase to 200mg three times a day for one week; then remain on 200mg three times a day for two weeks.
Interventions
Mexiletine is a sodium channel blocker shown to be effective in reducing myotonia in a multi-centre randomised trial.
Lamotrigine is an alternative sodium channel blocker that has been shown to be effective in one randomised controlled trial. It is currently used as a licensed medication for other neurological conditions.
Eligibility Criteria
You may qualify if:
- adults (≥ 18years),
- genetically confirmed non-dystrophic myotonia (NDM),
- presence of symptomatic myotonia as reported by the participant.
You may not qualify if:
- concomitant medical conditions that would preclude the use of mexiletine or lamotrigine,
- evidence of severe kidney disease or severe liver impairment \[estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation \<60ml/min/1.73m2\],
- pregnant or breastfeeding women,
- participation in other treatment studies \<30days before enrolment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University College London Hospital
London, WC1N 3BG, United Kingdom
Related Publications (1)
Vivekanandam V, Skorupinska I, Jayaseelan DL, Matthews E, Barohn RJ, McDermott MP, Hanna MG. Mexiletine versus lamotrigine in non-dystrophic myotonias: a randomised, double-blind, head-to-head, crossover, non-inferiority, phase 3 trial. Lancet Neurol. 2024 Oct;23(10):1004-1012. doi: 10.1016/S1474-4422(24)00320-X.
PMID: 39304240DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 11, 2021
First Posted
August 23, 2021
Study Start
August 12, 2021
Primary Completion
August 1, 2023
Study Completion
April 2, 2024
Last Updated
November 2, 2022
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will not share
Request for sharing anonymised data can be made to the Chief Investigator (CI) for discussion/consideration.