Clinical Outcome Measures in Myotonic Dystrophy Type 2

Myotonic Dystrophy Type 2 Clinical Trial

— COMEDY-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03603171
• Other study ID #: KlinikumUM
• Status: Completed
• Start date: July 1, 2018
• Est. completion date: February 1, 2020

Study information

• Verified date: February 2020
• Source: Klinikum der Universitaet Muenchen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 1, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

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.

Related Conditions & MeSH terms

• Myotonic Dystrophy
• Myotonic Dystrophy Type 2

Intervention

Diagnostic Test:
• DM1-ActivC
A Rasch-built activity and participation scale for clinical use in myotonic dystrophy type 1 (DM1)
• R-PAct
A Rasch-built Pompe-specific activity scale.
• Beck depression inventory
A self-reported depression inventory administered verbally or self administered.
• 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.
• 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
• Fatigue and Daytime Sleepiness Scale
A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1.
• Myotonia Behaviour scale
It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life
• 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.
• 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.
• 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.
• 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.
• Scale for Assessment and Rating of Ataxia
SARA is a clinical scale which assesses a range of different impairments in cerebellar ataxia.
• Berg balance scale
It is a 14 item objective measure designed to assess static balance and fall risk in adult populations
• Quick motor function test
Assessment of proximal motor function.
• 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.
• 30 seconds sit to stand test
It is a measurement that assesses functional lower extremity strenght in older adults.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Germany	Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen Munich, Germany	Munich	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Prof. Dr. Benedikt Schoser

Country where clinical trial is conducted

Germany, 

References & Publications (4)

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. — View Citation

Okkersen K, Jimenez-Moreno C, Wenninger S, Daidj F, Glennon J, Cumming S, Littleford R, Monckton DG, Lochmüller 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. — View 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. Review. — View Citation

Wood L, Bassez G, van Engelen B, Lochmüller 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	MIRS-2	Development of a muscle impairment staging score	10 months
Primary	Quick motor function test (QMFT)	A test for assessing motor function.	6 months
Primary	DM1-ActivC	A Rasch-built DM1 activity and participation scale for clinical use	6 months
Secondary	R-PAct	A Rasch-built Pompe-specific activity scale	6 months
Secondary	Beck depression inventory (BDI-II)	A self-reported depression inventory administered verbally or self administered.	6 months
Secondary	McGill pain questionnaire (MPQ-sf)	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.	6 months
Secondary	Brief Pain Inventory Short-Form (BPI-sf)	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.	6 months
Secondary	Fatigue and Daytime Sleepiness Scale (FDSS)	A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1.	6 months
Secondary	Myotonia Behaviour scale (MBS)	It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life.	6 months
Secondary	Myotonia (from Individualised Neuromuscular Quality of Life Questionnaire)	A subscale derived from the INQoL questionnaire. 3 questions regarding stiffness and myotonia.	6 months
Secondary	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.	6 months
Secondary	Scale for Assessment and Rating of Ataxia (SARA)	It is a clinical scale which assesses a range of different impairments in cerebellar ataxia.	6 months
Secondary	Berg balance scale (BBS)	It is a 14 item objective measure designed to assess static balance and fall risk in adult populations.	6 months
Secondary	Pressure pain threshold (PPT)	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.	6 months
Secondary	Manual muscle testing (MMT)	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.	6 months
Secondary	Quantitative muscle testing (QMT)	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.	6 months
Secondary	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.	6 months
Secondary	Functional Index-2 (only upper extremities)	Disease-specific functional outcome assessing muscle endurance. In this trial, only the part of the test for the upper extremities is used.	6 months
Secondary	30 seconds sit to stand test (30CST)	It is a measurement that assesses functional lower extremity strength in older adults.	6 months
Secondary	Six-minute-walking test (6MWT)	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.	6 months