Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: Clinical Outcome Measures in Myotonic Dystrophy Type 2

Summary: A monocentric, longitudinal, observational case-control study in patients with Myotonic Dystrophy type 2 (DM2). At least 60 DM2 will be evaluated through a battery of patients reported Outcomes (PROs) and clinical Outcome Measures (OMs), in order to define suitable OMs for DM2 and propose a disease specific severity scale. Patients will be re-evaluated after 6 months. An age and gender-matched control cohort will be assessed.

Detailed description: Myotonic dystrophy type 2 (DM2) is an autosomal dominant, chronic progressive multisystemic disorder. Typical symptoms of DM2 include progressive proximal muscle weakness and wasting, often combined with axial and anterior neck muscles involvement, myotonia, muscular pain, fatigue and cataracts. The estimated prevalence is approximately 1 per 100,000 people, but in some nations as Germany the DM2 frequency is much higher than and close to 1.12.000. Compared to DM1 it has a relatively short history, as the genetic base and RNA pathogenesis have been clarified in 2003. In order to evaluate specific clinical aspects of DM2 and disease progression, the development and validation of ad-hoc tests is a unmet need in the neuromuscular field. Today, only a few outcome measures were used systematically in DM2 patients, and none of them provide so far a validation of a clinical meaningful difference for an interventional clinical trial.
  The aims of this monocentric, observational, case-control study are:
  1. select and validate patient reported outcomes (PRO) and outcome measures (OM) in a large group of DM2 patient
  2. Propose a DM2-specific scale of disease severity
  3. collecting additional information regarding the phenotype and the progression of the disease;
  4. identify differences between subgroups (e.g. age, sex, years of disease).
  Participants will be recruited from the German-Swiss Registry for Myotonic Dystrophy and the internal database of the Friedrich-Baur-Institute (FBI), Department of Neurology, Ludwig-Maximilian-University, Munich, Germany. A total of at least 60 male and female patients with no age limit and with genetically proven DM2 will be included. Forty age and gender-matched controls will be also assessed.
  During the first evaluation of the DM2 and the controls group, the following PROs and OMs will be evaluated:
  General survey (Comorbidity, BMI, familiarity, onset, etc…), DM1-ActivC, R-Pact, FDSS, McGill pain questionnaire - short form, Brief pain inventory - short form, Beck depression inventory, Myotonia behaviour scale, Myotonia subscale from INQoL, Hand opening time, pressure pain threshold, manual and quantitative muscle testing, SARA scale, Berg balance scale, QMFT, GSGC, 30 second sit and stand test, FI-2 (only for upper extremities), 6-MWT.
  After six months a second evaluation of the DM2 group will be performed, in which all PROs and OMs except the general survey will be repeated.
  Data analysis will provide descriptive statistic and a complete validity and reliability informations. On the basis of these results, a disease specific severity scale will be proposed for the clinical use.

Eligibility: Inclusion Criteria:
  -  Genetically confirmed myotonic dystrophy type 2
  -  Able to provide informed consent
  Exclusion Criteria:
  -  Invalidating diseases not related with DM2 (e.g. Stroke).
  -  Subject participating in another clinical trial (other than registries) concurrently or within 30 days prior to screening for entry into this study.
  -  Unable to complete study questionnaires.

Relevance to patient case: not relevant