Clinical Outcome Measures in Myotonic Dystrophy Type 2

Completed

• Conditions: Myotonic Dystrophy Type 2
• Interventions: Diagnostic Test: DM1-ActivC; Diagnostic Test: R-PAct; Diagnostic Test: Beck depression inventory; Diagnostic Test: McGill pain questionnaire; Diagnostic Test: Brief Pain Inventory Short-Form; Diagnostic Test: Fatigue and Daytime Sleepiness Scale; Diagnostic Test: Myotonia Behaviour scale; Diagnostic Test: Hand opening time; Diagnostic Test: Pressure pain threshold; Diagnostic Test: Manual muscle testing; Diagnostic Test: Quantitative muscle testing; Diagnostic Test: Scale for Assessment and Rating of Ataxia; Diagnostic Test: Berg balance scale; Diagnostic Test: Quick motor function test; Diagnostic Test: GSGC; Diagnostic Test: 30 seconds sit to stand test; Diagnostic Test: Functional Index-2; Diagnostic Test: Six minute walking test; Diagnostic Test: Myotonia (from Individualised Neuromuscular Quality of Life Questionnaire)

• Registration Number: NCT03603171
• Lead Sponsor: Prof. Dr. Benedikt Schoser

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.

Study Timeline

• Study Start: 2018-07-01
• Study First Submitted: 2018-07-17
• Study First Submitted QC: 2018-07-26
• Study First Posted: 2018-07-27
• Primary Completion: 2019-12-31
• Status Verified: 2020-02
• Study Completion: 2020-02-01
• Last Update Submitted: 2020-02-19
• Last Update Posted: 2020-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
DM2 group	Beck depression inventory	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	R-PAct	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Myotonia Behaviour scale	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	DM1-ActivC	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Fatigue and Daytime Sleepiness Scale	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	30 seconds sit to stand test	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
Healthy controls group	Myotonia Behaviour scale	A group of gender and age-matched healthy controls.
DM2 group	McGill pain questionnaire	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Brief Pain Inventory Short-Form	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Pressure pain threshold	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Manual muscle testing	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Six minute walking test	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Myotonia (from Individualised Neuromuscular Quality of Life Questionnaire)	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
Healthy controls group	Brief Pain Inventory Short-Form	A group of gender and age-matched healthy controls.
Healthy controls group	Quick motor function test	A group of gender and age-matched healthy controls.
DM2 group	GSGC	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Functional Index-2	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
Healthy controls group	R-PAct	A group of gender and age-matched healthy controls.
Healthy controls group	McGill pain questionnaire	A group of gender and age-matched healthy controls.
Healthy controls group	Pressure pain threshold	A group of gender and age-matched healthy controls.
Healthy controls group	Berg balance scale	A group of gender and age-matched healthy controls.
Healthy controls group	30 seconds sit to stand test	A group of gender and age-matched healthy controls.
DM2 group	Hand opening time	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Quantitative muscle testing	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Berg balance scale	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
DM2 group	Quick motor function test	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
Healthy controls group	Hand opening time	A group of gender and age-matched healthy controls.
DM2 group	Scale for Assessment and Rating of Ataxia	Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.
Healthy controls group	DM1-ActivC	A group of gender and age-matched healthy controls.
Healthy controls group	Beck depression inventory	A group of gender and age-matched healthy controls.
Healthy controls group	Fatigue and Daytime Sleepiness Scale	A group of gender and age-matched healthy controls.
Healthy controls group	Scale for Assessment and Rating of Ataxia	A group of gender and age-matched healthy controls.
Healthy controls group	Functional Index-2	A group of gender and age-matched healthy controls.
Healthy controls group	Myotonia (from Individualised Neuromuscular Quality of Life Questionnaire)	A group of gender and age-matched healthy controls.
Healthy controls group	Manual muscle testing	A group of gender and age-matched healthy controls.
Healthy controls group	Quantitative muscle testing	A group of gender and age-matched healthy controls.
Healthy controls group	GSGC	A group of gender and age-matched healthy controls.
Healthy controls group	Six minute walking test	A group of gender and age-matched healthy controls.

Primary Outcome Measures

Name	Time	Method
DM1-ActivC	6 months	A Rasch-built DM1 activity and participation scale for clinical use
Quick motor function test (QMFT)	6 months	A test for assessing motor function.

Secondary Outcome Measures

Name	Time	Method
Myotonia (from Individualised Neuromuscular Quality of Life Questionnaire)	6 months	A subscale derived from the INQoL questionnaire. 3 questions regarding stiffness and myotonia.
Scale for Assessment and Rating of Ataxia (SARA)	6 months	It is a clinical scale which assesses a range of different impairments in cerebellar ataxia.
Berg balance scale (BBS)	6 months	It is a 14 item objective measure designed to assess static balance and fall risk in adult populations.
Six-minute-walking test (6MWT)	6 months	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.
Hand opening time	6 months	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.
Pressure pain threshold (PPT)	6 months	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 oft wo measurements was recorded.
Fatigue and Daytime Sleepiness Scale (FDSS)	6 months	A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1.
GSGC	6 months	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.
Functional Index-2 (only upper extremities)	6 months	Disease-specific functional outcome assessing muscle endurance. In this trial, only the part of the test for the upper extremities is used.
Beck depression inventory (BDI-II)	6 months	A self-reported depression inventory administered verbally or self administered.
Brief Pain Inventory Short-Form (BPI-sf)	6 months	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.
Myotonia Behaviour scale (MBS)	6 months	It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life.
R-PAct	6 months	A Rasch-built Pompe-specific activity scale
McGill pain questionnaire (MPQ-sf)	6 months	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.
Manual muscle testing (MMT)	6 months	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 measurements is considered.
Quantitative muscle testing (QMT)	6 months	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.
30 seconds sit to stand test (30CST)	6 months	It is a measurement that assesses functional lower extremity strength in older adults.

Trial Locations

Locations (1)

Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen Munich, Germany; 🇩🇪 Munich, Bavaria, Germany