Myotonic Dystrophy Type 2
Conditions
Keywords
myotonic dystrophy type 2, outcome scale, muscle strength, outcome measures, disease specific severity scale
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.
Interventions
DIAGNOSTIC_TESTDM1-ActivC
A Rasch-built activity and participation scale for clinical use in myotonic dystrophy type 1 (DM1)
DIAGNOSTIC_TESTR-PAct
A Rasch-built Pompe-specific activity scale.
DIAGNOSTIC_TESTBeck depression inventory
A self-reported depression inventory administered verbally or self administered.
DIAGNOSTIC_TESTMcGill 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_TESTBrief 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_TESTFatigue and Daytime Sleepiness Scale
A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1.
DIAGNOSTIC_TESTMyotonia Behaviour scale
It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life
DIAGNOSTIC_TESTHand 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_TESTPressure 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_TESTManual 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_TESTQuantitative 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_TESTScale for Assessment and Rating of Ataxia
SARA is a clinical scale which assesses a range of different impairments in cerebellar ataxia.
DIAGNOSTIC_TESTBerg balance scale
It is a 14 item objective measure designed to assess static balance and fall risk in adult populations
DIAGNOSTIC_TESTQuick motor function test
Assessment of proximal motor function.
DIAGNOSTIC_TESTGSGC
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_TEST30 seconds sit to stand test
It is a measurement that assesses functional lower extremity strenght in older adults.
DIAGNOSTIC_TESTFunctional 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_TESTSix 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_TESTMyotonia (from Individualised Neuromuscular Quality of Life Questionnaire)
A subscale derived from the Individualised Neuromuscular Quality of Life Questionnaire (INQoL). 3 questions reguarding stiffness/myotonia.
Sponsors
Prof. Dr. Benedikt Schoser
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| R-PAct | 6 months | A Rasch-built Pompe-specific activity scale |
| Beck depression inventory (BDI-II) | 6 months | A self-reported depression inventory administered verbally or self administered. |
| 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. |
| 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. |
| Fatigue and Daytime Sleepiness Scale (FDSS) | 6 months | A Rasch-built combined fatigue and daytime sleepiness scale (FDSS) specifically designed for patients with DM1. |
| Myotonia Behaviour scale (MBS) | 6 months | It consists of six framed sentences, which most closely describe the impact of the stiffness on everyday life. |
| Myotonia (from Individualised Neuromuscular Quality of Life Questionnaire) | 6 months | A subscale derived from the INQoL questionnaire. 3 questions regarding stiffness and myotonia. |
| 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. |
| Berg balance scale (BBS) | 6 months | It is a 14 item objective measure designed to assess static balance and fall risk in adult populations. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 30 seconds sit to stand test (30CST) | 6 months | It is a measurement that assesses functional lower extremity strength in older adults. |
Other
| Measure | Time frame | Description |
|---|---|---|
| MIRS-2 | 10 months | Development of a muscle impairment staging score |
Countries
Germany
Outcome results
None listed