Clinical Outcome Measures in Myotonic Dystrophy Type 2
Condition: Myotonic Dystrophy Type 2
MeSH terms: Myotonic Dystrophy
Study type: Observational

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.
    

Intervention name(s): DM1-ActivC; R-PAct; Beck depression inventory; McGill pain questionnaire; Brief Pain Inventory Short-Form; Fatigue and Daytime Sleepiness Scale; Myotonia Behaviour scale; Hand opening time; Pressure pain threshold; Manual muscle testing; Quantitative muscle testing; Scale for Assessment and Rating of Ataxia; Berg balance scale; Quick motor function test; GSGC; 30 seconds sit to stand test; Functional Index-2; Six minute walking test; Myotonia (from Individualised Neuromuscular Quality of Life Questionnaire)
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test
Intervention description(s): A Rasch-built activity and participation scale for clinical use in myotonic dystrophy type 1 (DM1); A Rasch-built Pompe-specific activity scale.; A self-reported depression inventory administered verbally or self administered.; The short form of the MPQ, used to evaluate the qualitative aspect of pain and categorized in three dimensions of pain experience: sensory qualities, affective qualities and overall intensity.; A 9 item self-administered questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning; A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1.; It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life; A simple test to evaluate clinical myotonia: the patient makes a tight fist for 5 seconds, then rapidly open them and the opening time is measured.; Thresholds for pressure pain were obtained over eight muscles on the left and right side of the body: extensor digitorum communis, deltoid, quadriceps and anterior tibialis. The average value of two measurements will be recorded.; The patient is instructed to hold the corresponding limb or appropriate body part to be tested at the end of its available range while the practitioner provides opposing manual resistance. The strength is measured by the modified-MRC scale. The average value of two mesurements is considered. The following muscles were assessed: neck flexors and extensors, hip flexors and extensors, knee flexors and extensors, shoulder abductors, elbow flexors and extensors, ankle dorsiflexors and plantar flexors, wrist flexors and Extensors, digit flexors and extensors and thumb abductors.; Strength testing using sophisticated strength measuring devices during an isometric contraction. The average value of two measurements is considered; in case of difference > 10% between measurements, a third attempt is performed. The following muscles are assessed: neck flexors and extensors, hip flexors and extensors, knee flexors and extensors, shoulder abductors, elbow flexors and extensors, ankle dorsiflexors and plantar flexors, wrist flexors and extensors and digit flexors.; SARA is a clinical scale which assesses a range of different impairments in cerebellar ataxia.; It is a 14 item objective measure designed to assess static balance and fall risk in adult populations; Assessment of proximal motor function.; GSGC score provides a detailed picture of motor function by including quantitative measures of four main motor performances (Gait, Walking, Stair, Gower's) and a qualitative global assessment of the manner to accomplish them.; It is a measurement that assesses functional lower extremity strenght in older adults.; Disease-specific functional outcome assessing muscle endurance. In this trial, only the part of the test for the upper extremities is used.; It is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity.; A subscale derived from the Individualised Neuromuscular Quality of Life Questionnaire (INQoL). 3 questions reguarding stiffness/myotonia.
Other intervention name(s): BDI-II; MPQ-sf; BPI-sf; FDSS; MBS; PPT; MMT; QMT; SARA; BBS; QMFT; 30CST; FI-2; 6MWT; InQoL
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with Myotonic Dystrophy type 2, without limitations regarding age of onset,
        disease duration or physical impairment related to the disease.
      
Keywords: myotonic dystrophy type 2; outcome scale; muscle strength; outcome measures; disease specific severity scale