Clinical trial NCT03603171: Clinical Outcome Measures in Myotonic Dystrophy Type 2
Official title: Observational Trial in Myotonic Dystrophy Type 2 to Define Specific Clinical Outcome Measures
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myotonic Dystrophy Type 2
Keywords: myotonic dystrophy type 2
outcome scale
muscle strength
outcome measures
disease specific severity scale
Lead sponsor: LMU Klinikum
Sponsor class: OTHER
First posted: 2018-07-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
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.

Brief 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 criteria: 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.

Primary outcomes:
measure: Quick motor function test (QMFT)
timeFrame: 6 months
measure: DM1-ActivC
timeFrame: 6 months
Secondary outcomes:
measure: R-PAct
timeFrame: 6 months
measure: Beck depression inventory (BDI-II)
timeFrame: 6 months
measure: McGill pain questionnaire (MPQ-sf)
timeFrame: 6 months
measure: Brief Pain Inventory Short-Form (BPI-sf)
timeFrame: 6 months
measure: Fatigue and Daytime Sleepiness Scale (FDSS)
timeFrame: 6 months
measure: Myotonia Behaviour scale (MBS)
timeFrame: 6 months
measure: Myotonia (from Individualised Neuromuscular Quality of Life Questionnaire)
timeFrame: 6 months
measure: Hand opening time
timeFrame: 6 months
measure: Scale for Assessment and Rating of Ataxia (SARA)
timeFrame: 6 months
measure: Berg balance scale (BBS)
timeFrame: 6 months
measure: Pressure pain threshold (PPT)
timeFrame: 6 months
measure: Manual muscle testing (MMT)
timeFrame: 6 months
measure: Quantitative muscle testing (QMT)
timeFrame: 6 months
measure: GSGC
timeFrame: 6 months
measure: Functional Index-2 (only upper extremities)
timeFrame: 6 months
measure: 30 seconds sit to stand test (30CST)
timeFrame: 6 months
measure: Six-minute-walking test (6MWT)
timeFrame: 6 months
Other outcomes:
measure: MIRS-2
timeFrame: 10 months
Locations:
city: Munich
country: Germany
facility: Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen Munich, Germany
state: Bavaria
Study officials:
affiliation: Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen Munich, Germany
name: Benedikt Schoser, MD
role: STUDY_CHAIR
References:
citation: Okkersen K, Jimenez-Moreno C, Wenninger S, Daidj F, Glennon J, Cumming S, Littleford R, Monckton DG, Lochmuller H, Catt M, Faber CG, Hapca A, Donnan PT, Gorman G, Bassez G, Schoser B, Knoop H, Treweek S, van Engelen BGM; OPTIMISTIC consortium. Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial. Lancet Neurol. 2018 Aug;17(8):671-680. doi: 10.1016/S1474-4422(18)30203-5. Epub 2018 Jun 19.
citation: Wenninger S, Montagnese F, Schoser B. Core Clinical Phenotypes in Myotonic Dystrophies. Front Neurol. 2018 May 2;9:303. doi: 10.3389/fneur.2018.00303. eCollection 2018.
citation: Wood L, Bassez G, van Engelen B, Lochmuller H, Schoser B; 222nd ENMC workshop participants. 222nd ENMC International Workshop:: Myotonic dystrophy, developing a European consortium for care and therapy, Naarden, The Netherlands, 1-2 July 2016. Neuromuscul Disord. 2018 May;28(5):463-469. doi: 10.1016/j.nmd.2018.02.003. Epub 2018 Feb 12. No abstract available.
citation: Montagnese F, Mondello S, Wenninger S, Kress W, Schoser B. Assessing the influence of age and gender on the phenotype of myotonic dystrophy type 2. J Neurol. 2017 Dec;264(12):2472-2480. doi: 10.1007/s00415-017-8653-2. Epub 2017 Oct 30.
citation: Montagnese F, Rastelli E, Khizanishvili N, Massa R, Stahl K, Schoser B. Validation of Motor Outcome Measures in Myotonic Dystrophy Type 2. Front Neurol. 2020 Apr 21;11:306. doi: 10.3389/fneur.2020.00306. eCollection 2020.