Clinical Outcome Measures in Myotonic Dystrophy Type 2

NCT ID: NCT03603171

Last Updated: 2020-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-07-01

Study Completion Date

2020-02-01

Brief Summary

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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

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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

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Myotonic Dystrophy Type 2

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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DM2 group

Patients with Myotonic Dystrophy type 2 genetically confirmed, without limitation regarding age or disease onset.

DM1-ActivC

Intervention Type DIAGNOSTIC_TEST

A Rasch-built activity and participation scale for clinical use in myotonic dystrophy type 1 (DM1)

R-PAct

Intervention Type DIAGNOSTIC_TEST

A Rasch-built Pompe-specific activity scale.

Beck depression inventory

Intervention Type DIAGNOSTIC_TEST

A self-reported depression inventory administered verbally or self administered.

McGill pain questionnaire

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1.

Myotonia Behaviour scale

Intervention Type DIAGNOSTIC_TEST

It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life

Hand opening time

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

SARA is a clinical scale which assesses a range of different impairments in cerebellar ataxia.

Berg balance scale

Intervention Type DIAGNOSTIC_TEST

It is a 14 item objective measure designed to assess static balance and fall risk in adult populations

Quick motor function test

Intervention Type DIAGNOSTIC_TEST

Assessment of proximal motor function.

GSGC

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

It is a measurement that assesses functional lower extremity strenght in older adults.

Functional Index-2

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_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)

Intervention Type DIAGNOSTIC_TEST

A subscale derived from the Individualised Neuromuscular Quality of Life Questionnaire (INQoL). 3 questions reguarding stiffness/myotonia.

Healthy controls group

A group of gender and age-matched healthy controls.

DM1-ActivC

Intervention Type DIAGNOSTIC_TEST

A Rasch-built activity and participation scale for clinical use in myotonic dystrophy type 1 (DM1)

R-PAct

Intervention Type DIAGNOSTIC_TEST

A Rasch-built Pompe-specific activity scale.

Beck depression inventory

Intervention Type DIAGNOSTIC_TEST

A self-reported depression inventory administered verbally or self administered.

McGill pain questionnaire

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1.

Myotonia Behaviour scale

Intervention Type DIAGNOSTIC_TEST

It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life

Hand opening time

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

SARA is a clinical scale which assesses a range of different impairments in cerebellar ataxia.

Berg balance scale

Intervention Type DIAGNOSTIC_TEST

It is a 14 item objective measure designed to assess static balance and fall risk in adult populations

Quick motor function test

Intervention Type DIAGNOSTIC_TEST

Assessment of proximal motor function.

GSGC

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

It is a measurement that assesses functional lower extremity strenght in older adults.

Functional Index-2

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_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)

Intervention Type DIAGNOSTIC_TEST

A subscale derived from the Individualised Neuromuscular Quality of Life Questionnaire (INQoL). 3 questions reguarding stiffness/myotonia.

Interventions

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DM1-ActivC

A Rasch-built activity and participation scale for clinical use in myotonic dystrophy type 1 (DM1)

Intervention Type DIAGNOSTIC_TEST

R-PAct

A Rasch-built Pompe-specific activity scale.

Intervention Type DIAGNOSTIC_TEST

Beck depression inventory

A self-reported depression inventory administered verbally or self administered.

Intervention Type 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.

Intervention Type 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

Intervention Type DIAGNOSTIC_TEST

Fatigue and Daytime Sleepiness Scale

A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1.

Intervention Type DIAGNOSTIC_TEST

Myotonia Behaviour scale

It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Scale for Assessment and Rating of Ataxia

SARA is a clinical scale which assesses a range of different impairments in cerebellar ataxia.

Intervention Type DIAGNOSTIC_TEST

Berg balance scale

It is a 14 item objective measure designed to assess static balance and fall risk in adult populations

Intervention Type DIAGNOSTIC_TEST

Quick motor function test

Assessment of proximal motor function.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

30 seconds sit to stand test

It is a measurement that assesses functional lower extremity strenght in older adults.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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BDI-II MPQ-sf BPI-sf FDSS MBS PPT MMT QMT SARA BBS QMFT 30CST FI-2 6MWT InQoL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Prof. Dr. Benedikt Schoser

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Benedikt Schoser

Neurologist, senior physician

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Benedikt Schoser, MD

Role: STUDY_CHAIR

Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen Munich, Germany

Locations

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Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen Munich, Germany

Munich, Bavaria, Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 29934199 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29770119 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29550152 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29086017 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32373059 (View on PubMed)

Other Identifiers

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KlinikumUM

Identifier Type: -

Identifier Source: org_study_id

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