DM-IMT - Controlled, Randomized, Three-arm Intervention Study on the Safety and Efficacy of Regular Respiratory Muscle Training in Patients With Myotonic Dystrophy Type 1 (DM-IMT)

• ClinicalTrials.gov Identifier: NCT04052958
• Recruitment Status: Not yet recruiting
• First Posted: August 12, 2019
• Last Update Posted: August 12, 2019
• Sponsor: Klinikum der Universitaet Muenchen
• Information provided by (Responsible Party): Prof. Dr. Benedikt Schoser, Klinikum der Universitaet Muenchen

Study Description

Brief Summary:

For some diseases, regular respiratory muscle training could delay the start of ventilation. For DM1, however, there are no clinically high-quality studies. Only a case description from the year 2006 showed a missing improvement of the symptoms after respiratory muscle training in one patient, accordingly there are no recommendations in this issue. Within the scope of this monocentric, three-arm, controlled intervention study, 45 patients with genetically confirmed type 1 myotonic dystrophy will be randomized in three groups of 15 patients each, age-, gender- and symptom-corrected by the MUSCULAR IMPAIRMENT RATING SCALE (MIRS). The DM1 patients will receive regular respiratory muscle training for a period of 9 months. The aim of this study is to evaluate the safety and effectiveness of regular inspiratory strength-breathing muscle training on 15 patients, the safety and effectiveness of regular inspiratory endurance respiratory muscle training on 15 patients, and the comparison to the natural course in 15 patients without training. Subsequently, we will provide treatment recommendations for respiratory training in DM1.

Condition or disease	Intervention/treatment	Phase
Myotonic Dystrophy 1	Device: IMT - inspiratory muscle training	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: DM-IMT - Controlled, Randomized, Three-arm Intervention Study on the Safety and Efficacy of Regular Respiratory Muscle Training in Patients With Myotonic Dystrophy Type 1
• Estimated Study Start Date: August 15, 2019
• Estimated Primary Completion Date: December 15, 2020
• Estimated Study Completion Date: December 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Group 1: Strength Training; Respiratory muscle strength training	Device: IMT - inspiratory muscle training; respiratory strength or indurance training with respiratory therapy device
Active Comparator: Group 2: Endurance Training; Respiratory muscle endurance training	Device: IMT - inspiratory muscle training; respiratory strength or indurance training with respiratory therapy device
No Intervention: Group 3: Control group; no training of respiratory muscles

Outcome Measures

Primary Outcome Measures :

1. Safety of recurrent inspiratory muscle training [ Time Frame: nine months ]
   Intervention-related (serious) adverse events will be assessed as described in protocoll DM-IMT Version 1.2 (26/June/2019). For example a deterioration of > 15% of the FVC compared to the baseline measurements is defined as AE, as is the development of unusual myalgia of the respiratory muscles for more than 12 hours after the respiratory training. Detailed lists of patients experiencing adverse events or SAEs are reported. The severity of the adverse event is classified as mild, moderate or severe. Relationships of an AE to the training are categorized as unassociated, unlikely to be associated, possibly associated or associated. A separate list will be provided for patients who drop out of the study due to AEs. The frequency of adverse events leading to study termination is also summarized. Safety parameters also include lung function tests (PFT, including FVC, FEV1, MIP, MEP), physical examination, vital signs and clinical laboratory tests as required.

Secondary Outcome Measures :

1. Efficacy of recurrent inspiratory muscle strength training in 15 patients with type 1 myotonic dystrophy measured by MIP. [ Time Frame: nine months ]
   The efficacy of the respiratory training is determined by the results of Maximal inspiratory pressure (MIP).
2. Efficacy of recurrent inspiratory muscle endurance training in 15 patients with type 1 myotonic dystrophy measured by MIP. [ Time Frame: nine months ]
   The efficacy of the respiratory training is determined by the results of Maximal inspiratory pressure (MIP).
3. Efficacy of recurrent inspiratory muscle strength training in 15 patients with type 1 myotonic dystrophy measured by MEP. [ Time Frame: nine months ]
   The efficacy of the respiratory training is determined by the results of Maximal exspiratory pressure (MEP).
4. Efficacy of recurrent inspiratory muscle endurance training in 15 patients with type 1 myotonic dystrophy measured by MEP. [ Time Frame: nine months ]
   The efficacy of the respiratory training is determined by the results of Maximal exspiratory pressure (MEP).
5. Efficacy of recurrent inspiratory muscle strength training in 15 patients with type 1 myotonic dystrophy measured by FVC. [ Time Frame: nine months ]
   The efficacy of the respiratory training is determined by the results of Forced Vital capacity (FVC).
6. Efficacy of recurrent inspiratory muscle endurance training in 15 patients with type 1 myotonic dystrophy measured by FVC. [ Time Frame: nine months ]
   The efficacy of the respiratory training is determined by the results of Forced Vital capacity (FVC).
7. Efficacy of recurrent inspiratory muscle strength training in 15 patients with type 1 myotonic dystrophy measured by FEV1. [ Time Frame: nine months ]
   The efficacy of the respiratory training is determined by the results of Forced Expiratory Volume in 1 second (FEV1).
8. Efficacy of recurrent inspiratory muscle endurance training in 15 patients with type 1 myotonic dystrophy measured by FEV1. [ Time Frame: nine months ]
   The efficacy of the respiratory training is determined by the results of Forced Expiratory Volume in 1 second (FEV1).
9. Efficacy of recurrent inspiratory muscle strength training in 15 patients with type 1 myotonic dystrophy measured by pCO2. [ Time Frame: nine months ]
   The efficacy of the respiratory training is determined by the results of pCO2 in capillary blood gas analysis.
10. Efficacy of recurrent inspiratory muscle endurance training in 15 patients with type 1 myotonic dystrophy measured by pCO2. [ Time Frame: nine months ]
    The efficacy of the respiratory training is determined by the results of pCO2 in capillary blood gas analysis.
11. Efficacy of recurrent inspiratory muscle strength training in 15 patients with type 1 myotonic dystrophy measured by pO2. [ Time Frame: nine months ]
    The efficacy of the respiratory training is determined by the results of pO2 in capillary blood gas analysis.
12. Efficacy of recurrent inspiratory muscle endurance training in 15 patients with type 1 myotonic dystrophy measured by pO2. [ Time Frame: nine months ]
    The efficacy of the respiratory training is determined by the results of pO2 in capillary blood gas analysis.
13. Efficacy of recurrent inspiratory muscle strength training in 15 patients with type 1 myotonic dystrophy measured by pH. [ Time Frame: nine months ]
    The efficacy of the respiratory training is determined by the results of pH in capillary blood gas analysis.
14. Efficacy of recurrent inspiratory muscle endurance training in 15 patients with type 1 myotonic dystrophy measured by pH. [ Time Frame: nine months ]
    The efficacy of the respiratory training is determined by the results of pH in capillary blood gas analysis.
15. Efficacy of recurrent inspiratory muscle endurance training in 15 patients with type 1 myotonic dystrophy measured by 6-minute-walk-test. [ Time Frame: nine months ]
    The efficacy of the respiratory training is determined by the results of 6-minute-walk-test.
16. Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training compared to patients without training, measured by DM1-Activ. [ Time Frame: nine months ]
    Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training will be measured by the result of DM1-ACTIV, a Rasch-built DM activity and participation scale for clinical use.
17. Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training compared to patients without training, measured by FDSS. [ Time Frame: nine months ]
    Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training will be measured by the result of the FDSS - FATIGUE AND DAYTIME SLEEPINESS SCALE, a Rasch-built combined fatigue and daytime sleepiness scale specifically designed for patients with DM1.
18. Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training compared to patients without training, measured by the questionnaire Respicheck. [ Time Frame: nine months ]
    Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training will be measured by the result of the RESPICHECK, a questionnaire on clinical symptoms of respiratory insufficiency.
19. Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training compared to patients without training, measured by a physical examination. [ Time Frame: nine months ]
    Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training will be measured by the result of the physical examination.
20. Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training compared to patients without training, using the 6-minute-walk-test. [ Time Frame: nine months ]
    Impact on the quality of life and muscular performance in DM1 patients after recurrent respiratory muscle training will be measured by the result of the 6-minute-walk-test.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• the patient is willing and able to provide a signed informed consent form
• the patient is ≥ 18 years old
• the diagnosis of type 1 myotonic dystrophy has been confirmed by molecular genetics
• the patient is able and willing to perform pulmonary function tests (PFT) and blood sampling for capillary blood gas analysis (pO2, pCO2) throughout the study, to keep a diary and to complete questionnaires

Exclusion Criteria:

• the patient requires invasive ventilation (non-invasive ventilation is allowed).
• the patient uses non-invasive ventilation more than 16h/day.
• the patient participates in another clinical study that involves therapy.
• the patient cannot perform pulmonary function tests (PFT).
• the patient is diagnosed with central sleep apnea in polysomnography and not sufficiently treated with NIV ventilation.
• the patient is diagnosed with obstructive sleep apnea and not sufficiently treated with NIV ventilation.
• the patient cannot meet the requirements of the study, according to the investigator.
• the patient is unable to complete a 6-minute walking test

Contacts and Locations

Contacts

Contact: Stephan Wenninger, Dr.med.; +49 89440057470; stephan.wenninger@med.uni-muenchen.de

Contact: Benedikt Schoser, Prof.Dr.; +49 89440057470; benedikt.schoser@med.uni-muenchen.de

Locations

Germany

Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen Munich, Germany; Not yet recruiting

Munich, Bavaria, Germany, 80336

Contact: Benedikt Schoser, MD +4989440057470 bschoser@med.uni-muenchen.de

Contact: Stephan Wenninger, MD +4989440057470 stephan.wenninger@med.uni-muenchen.de

Sponsors and Collaborators

Klinikum der Universitaet Muenchen

Investigators

• Principal Investigator: Stephan Wenninger, Dr.med.; Neurologist

  Study Documents (Full-Text)

Documents provided by Prof. Dr. Benedikt Schoser, Klinikum der Universitaet Muenchen:

Study Protocol  [PDF] June 26, 2019

More Information

• Responsible Party: Prof. Dr. Benedikt Schoser, Neurologist, Senior Physician, Klinikum der Universitaet Muenchen
• ClinicalTrials.gov Identifier: NCT04052958 History of Changes
• Other Study ID Numbers: Version 1.2 (26. Juni 2019)
• First Posted: August 12, 2019
• Last Update Posted: August 12, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Myotonic Dystrophy; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn