NCT03603171

Clinical Outcome Measures in Myotonic Dystrophy Type 2

Observational Trial in Myotonic Dystrophy Type 2 to Define Specific Clinical Outcome Measures

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 60 (actual)
• Sponsor: Prof. Dr. Benedikt Schoser · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Accepted

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.

Conditions

• Myotonic Dystrophy Type 2

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	DM1-ActivC	A Rasch-built activity and participation scale for clinical use in myotonic dystrophy type 1 (DM1)
DIAGNOSTIC_TEST	R-PAct	A Rasch-built Pompe-specific activity scale.
DIAGNOSTIC_TEST	Beck depression inventory	A self-reported depression inventory administered verbally or self administered.
DIAGNOSTIC_TEST	McGill pain questionnaire	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.
DIAGNOSTIC_TEST	Brief Pain Inventory Short-Form	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
DIAGNOSTIC_TEST	Fatigue and Daytime Sleepiness Scale	A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1.
DIAGNOSTIC_TEST	Myotonia Behaviour scale	It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life
DIAGNOSTIC_TEST	Hand opening time	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.
DIAGNOSTIC_TEST	Pressure pain threshold	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.
DIAGNOSTIC_TEST	Manual muscle testing	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.
DIAGNOSTIC_TEST	Quantitative muscle testing	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.
DIAGNOSTIC_TEST	Scale for Assessment and Rating of Ataxia	SARA is a clinical scale which assesses a range of different impairments in cerebellar ataxia.
DIAGNOSTIC_TEST	Berg balance scale	It is a 14 item objective measure designed to assess static balance and fall risk in adult populations
DIAGNOSTIC_TEST	Quick motor function test	Assessment of proximal motor function.
DIAGNOSTIC_TEST	GSGC	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.
DIAGNOSTIC_TEST	30 seconds sit to stand test	It is a measurement that assesses functional lower extremity strenght in older adults.
DIAGNOSTIC_TEST	Functional Index-2	Disease-specific functional outcome assessing muscle endurance. In this trial, only the part of the test for the upper extremities is used.
DIAGNOSTIC_TEST	Six minute walking test	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.
DIAGNOSTIC_TEST	Myotonia (from Individualised Neuromuscular Quality of Life Questionnaire)	A subscale derived from the Individualised Neuromuscular Quality of Life Questionnaire (INQoL). 3 questions reguarding stiffness/myotonia.

Timeline

• Start date: 2018-07-01
• Primary completion: 2019-12-31
• Completion: 2020-02-01
• First posted: 2018-07-27
• Last updated: 2020-02-20

Locations

1 site across 1 country: Germany