Myotonic Dystrophy 1, Myotonic Dystrophy 2
Conditions
Keywords
Ambispective, Retrospective, Prospective, Natural History, DM-Scope Registry, Observational, DM1, DM2
Brief summary
This natural history observational study is being conducted to follow patients with DM1 or DM2 over a 2 year period to study the presence of myotonia, how it's perceived and its impact on patients quality of life. This study will be conducted at 6 study sites located in France.100 Patients will be recruited from the DM Scope Registry only. The study involves two parts. Part 1 will look back up to 18 months of past medical history that is already available from the DM Scope Registry. Part 2 will follow the same patients for 24 months, with study visits at Day 1 (Baseline), 12 months and 24 months. The goal is to better understand how myotonia symptoms and complications such as heart and other systemic problems develop and change over time. A smaller, sub-study will take place at one site, using new exploratory methods in about 40 patients with DM1 who are also part of the Track DM Study.
Detailed description
The rationale of the study is to gather longitudinal data on patients with DM1 and DM2 in order to better understand disease progression and evolution of myotonia and other symptoms and their associated complications/risks, particularly in relation to cardiac and other systemic manifestations. The primary objective is to investigate the evolution of myotonia presence, perception and its impact on the burden of disease over time in patients with Myotonic dystrophy type 1 (DM1) and type 2 (DM2). The secondary objective is to evaluate the progression of other DM-related multisystemic symptom manifestation such as cardiac, pulmonary, gastrointestinal (GI), hepatic, and renal impairments/disorders, muscle weakness, stumbling and falls in DM patients over 24-months. Additionally, the study will assess the use of pharmacological and non-pharmacological treatments for myotonia during the data collection period. All of the patients will be recruited through the DM-Scope Registry. The registry database will be the source of the retrospective data to be used in the study. The study will begin with a detailed retrospective medical history assessment (up to -18 months to baseline) based on the annual routine DM-scope visits in the database. This will provide a comprehensive view of the patients' health status before the study. The 24-month prospective assessment period visits will occur at baseline, 12 months and 24 months. This approach allows for detailed tracking of disease progression and associated complications/risks over time. The exploratory sub-study aims to broaden the understanding of DM1 pathophysiology by incorporating biophysical, functional, and behavioral measurements beyond traditional motor function and muscle strength. It also aims to evaluate the reliability of several innovative assessments, including advanced tools to deliver a multidimensional view of disease progression.
Interventions
None listed
Sponsors
Lupin Ltd.
Lupin Atlantis Holdings S.A.
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Enrolled in DM-scope registry genetically diagnosed with DM1 or DM2. * Affiliation or beneficiary of a social security system or of such a regime. * Ability to comprehend and willingness to sign an informed consent (ICF). * Male or non-pregnant female ≥18 years of age at screening. * Body Mass Index (BMI) of 18.5 kg/m2 to 30 kg/m2, and weight ≥45 kg. * Medical history data covering up to 18 months prior to enrollment. * Clinical sign of myotonia * DM1 patients only - Muscular impairment rating scale (MIRS) score of 2, 3 or 4. * Be able to walk independently 10 meters (cane, walker, orthoses allowed).
Exclusion criteria
* No informed consent. * Pregnant or lactating women. * Subjects benefiting from laws aimed at protecting vulnerable adults: subjects being deprived of liberty by judicial or administrative decision, subjects under guardianship /curatorship. * Any medical condition or serious medical illness which in the opinion of the Investigator, precludes the participant's participation in the study or the participant is unlikely to comply with the protocol-defined procedures and therefore is unlikely to complete the study. * Medical conditions that could affect hand functioning including (but not limited to) rheumatoid arthritis, Dupuytren's contracture, hand deformity, severe arthritis or any other medical condition (other than DM1/DM2) that would significantly impact ambulation. * Patients with no documented record of myotonia assessment in the clinical records of the DM-scope database or myotonia absence at last visit prior to study enrolment. * Not able to perform study specific performance tests and evaluations e.g. hand grip dynamometry, 10mWT, etc. (in the opinion of the investigator). * Treatment with mexiletine within 18 months prior to baseline (Day 1).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in stiffness severity assessed by Visual Analog Scale (VAS) | Baseline to Month 24 | Absolute change in VAS stiffness score (0-100mm) between Baseline and Month 12 |
| Change in myotonia severity assessed by the Myotonia Behavior Scale (MBS) | Baseline to Month 24 | Absolute change in MBS score (1-6) between Baseline and Month 24. |
| Change in disease-related activity and participation assessed by DM1-Activ | Baseline to Month 24 | Absolute change in DM1-Activ score (0-100) between Baseline and Month 24. |
| Change in health-related quality of life assessed by the Individualized Neuromuscular Quality of Life Questionnaire (INQoL) | Baseline to Month 24 | Absolute change in INQoL: symptom subscores, life-domain subscores, overall total score, and treatment impact score (0-4 Likert) between Baseline and Month 24. |
| Change in walking performance assessed by the 10-Meter Walk Test (10mWT) | Baseline to Month 24 | Absolute change in 10mWT (sec) performance between Baseline and Month 24. |
| Change in mobility and functional performance assessed by the Timed Up and Go Test (TUG) | Baseline to Month 24 | Absolute change in TUG performance (sec) between Baseline and Month 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in cardiac function | Baseline and all scheduled study timepoints, including retrospective assessments up to 18 months before enrollment. | Assessment of cardiac manifestations of DM1 using ECG and echocardiography, including LVEF, heart rate, PR interval, QRS interval, QT interval (QTcB and QTcF), and classification of cardiac function status (Normal, Abnormal-Not Clinically Significant, Abnormal-Clinically Significant). |
| Progression of opthalmologic manifestations | Scheduled study timepoints, including retrospective assessments up to 18 months before enrollment. | Presence or absence of cataracts at each study timepoint |
| Change in respiratory function | Baseline and all scheduled study timepoints, including retrospective data up to 18 months. | Absolute change in respiratory function as measured by spirometry, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC ratio. |
| Change in Physical Examination Findings | Baseline and all scheduled study timepoints. | Assessment and absolute changes in physical examination parameters, including BMI (weight (kg)/Height (m2)) and other clinically relevant findings (CS/NCS) at each study timepoint. |
| Safety and Tolerability | Throughout study participation. | Evaluation of adverse events, clinical laboratory parameters (hematology and biochemistry) and concomitant medication use. |
| Change in Gastrointestinal (GI) manifestations | Baseline and all scheduled study timepoints, including retrospective assessments up to 18 months before enrollment. | Assessment of gastrointestinal and related symptoms using a specific questionnaire used in DM-scope, including age of onset, coughing while eating or drinking (response options: never or \<2 times/month, \>2 times/month, \>1 time/week, not investigated), feeling of food blockage, digestive difficulties (Yes/No, if yes, specify: constipation, diarrhea, alternating diarrhea-constipation), fecal incontinence, urinary incontinence, gastroesophageal reflux |
| Change in muscle-related manifestations | Baseline and all scheduled study timepoints. | Assessment of disease-related muscular symptoms including dysphagia, muscle pain assessed by VAS (0-100mm), hand-opening time after contraction (sec), and swallowing function assessed by the Timed Water Swallowing Test (sec). |
| Change in mobility and functional performance | Baseline and all scheduled study timepoints | Assessment of mobility and physical function, including number of accidental falls, 10-Meter Walk Test (10mWT), and Timed Up and Go Test (TUG). |
| Change in Quality of Life | Baseline and all scheduled study timepoints. | Assessment of health-related quality of life using the Individualized Neuromuscular Quality of Life Questionnaire (INQoL), including symptom subscales, life-domain subscales, total score, and treatment impact score. |
| Clinical Global Impression of disease severity and change | Baseline and all scheduled study timepoints | Assessment of disease severity using the Clinical Global Impression (CGI) scale (7-point scale from normal, not at all ill, to amongst the most extremely ill) at each study timepoint. |
Countries
France
Contacts
CONTACTDirector of Clinical Operations, Lupin Research Inc.
CONTACTHead, Global Medical Affairs & Clinical Development
STUDY_CHAIRAlla Zozulya-Weidenfeller, PhD
Lupin Atlantis Holdings S.A.
Outcome results
None listed