Respiratory Muscle Training in Patients With Spinal Muscular Atrophy (SMA).

NCT05632666 | Unknown DMC

• 1 other identifier: W.OB19-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to study respiratory muscle training in patients with Spinal Muscular Atrophy (SMA). The main questions it aims to answer are:

• Is a home-based individualized training program for the inspiratory and expiratory muscles feasible (good adherence and good acceptability)?
• Can a home-based individualized training program for the inspiratory and expiratory muscles increase the strength of these muscles? Participants will be asked to perform 10 training sessions per week, spread out over 5-7 days. Each training session consists of 30 breathing cycles through the inspiratory muscle trainer and 30 breathing cycles trough the expiratory muscle trainer. In the first four months of the study researchers will compare two groups to see if a higher trainings load is more effective. One group will start at a trainings load of 10% of their maximal inspiratory and expiratory muscle strength. The other group will start at a trainings load of 30% of their maximal inspiratory and expiratory muscle strength. This group also need to adjust the trainings load based on their perceived exertion. After four months all participants will train on a trainings load of 30% of their maximal inspiratory and expiratory muscle strength and adjust the trainings load based on their perceived exertion. The participants will come to the hospital for lung function tests every four months for 12 months.

Conditions

Spinal Muscular Atrophy

Keywords

Spinal Muscular Atrophy; Inspiratory Muscle Training; Expiratory Muscle Training; Maximum Inspiratory Mouth Pressure; Maximum Expiratory Mouth Pressure; Respiratory Muscle Training

Outcome Measures

Primary Outcomes (10)

• Maximal inspiratory mouth pressure (PImax)

  Maximal inspiratory mouth pressure in Centimeter of Water Column (cmH2O) assessed conform the European Respiratory Society/American Thoracic Society (ERS/ATS) recommendations. Reference values of Wilson et al. 1984 will be used to calculate % of predicted.

  Baseline

• Maximal inspiratory mouth pressure (PImax)

  Maximal inspiratory mouth pressure in Centimeter of Water Column (cmH2O) assessed conform the European Respiratory Society/American Thoracic Society (ERS/ATS) recommendations. Reference values of Wilson et al. 1984 will be used to calculate % of predicted.

  4 months

• Maximal inspiratory mouth pressure (PImax)

  Maximal inspiratory mouth pressure in Centimeter of Water Column (cmH2O) assessed conform the European Respiratory Society/American Thoracic Society (ERS/ATS) recommendations. Reference values of Wilson et al. 1984 will be used to calculate % of predicted.

  8 months

• Maximal inspiratory mouth pressure (PImax)

  Maximal inspiratory mouth pressure in Centimeter of Water Column (cmH2O) assessed conform the European Respiratory Society/American Thoracic Society (ERS/ATS) recommendations. Reference values of Wilson et al. 1984 will be used to calculate % of predicted.

  12 months

• Feasibility: adherence from baseline (M0) to 4 months visit (M4)

  The completion rate of the estimated number of training sessions over 4 months (\>80% of the participants have fulfilled the prescribed treatment = good adherence). Adherence will be monitored by a patient diary, the data saved in the POWERbreathe KHP2 and, two weekly telephone- or video calls by a physiotherapist.

  From baseline (M0) to 4 months visit (M4)

• Feasibility: adherence from 4 months (M4) to 8 months visit (M8)

  The completion rate of the estimated number of training sessions over 4 months (\>80% of the participants have fulfilled the prescribed treatment = good adherence). Adherence will be monitored by a patient diary, the data saved in the POWERbreathe KHP2 and, two weekly telephone- or video calls by a physiotherapist.

  From 4 months (M4) to 8 months visit (M8)

• Feasibility: adherence from 8 months (M8) to 12 months visit (M12)

  The completion rate of the estimated number of training sessions over 4 months (\>80% of the participants have fulfilled the prescribed treatment = good adherence). Adherence will be monitored by a patient diary, the data saved in the POWERbreathe KHP2 and, two weekly telephone- or video calls by a physiotherapist.

  From 8 months (M8) to 12 months visit (M12)

• Feasibility: acceptability

  The willingness to continue the training (\>5 = good acceptability) assessed with a Borg Scale (0-10)

  4 months

• Feasibility: acceptability

  The willingness to continue the training (\>5 = good acceptability) assessed with a Borg Scale (0-10)

  8 months

• Feasibility: acceptability

  The willingness to continue the training (\>5 = good acceptability) assessed with a Borg Scale (0-10)

  12 months

Secondary Outcomes (54)

• Maximal expiratory mouth pressure (PEmax)

  Baseline

• Maximal expiratory mouth pressure (PEmax)

  4 months

• Maximal expiratory mouth pressure (PEmax)

  8 months

• Maximal expiratory mouth pressure (PEmax)

  12 months

• Health related quality of life

  Baseline

Study Arms (2)

Active treatment group

EXPERIMENTAL

Other: Inspiratory and expiratory muscle training at a therapeutic intensity

Sham-controlled group

SHAM COMPARATOR

Other: Inspiratory and expiratory muscle training at a non-therapeutic intensity

Interventions

Inspiratory and expiratory muscle training at a therapeutic intensity OTHER

The active treatment group will receive inspiratory muscle training starting at a therapeutic intensity of 30% of maximum inspiratory mouth pressure (PImax) and expiratory muscle training starting at a therapeutic intensity of 30% of maximum expiratory mouth pressure (PEmax) for 4 months. In the active treatment group, the inspiratory and expiratory threshold (intensity) will be adjusted to the perceived exertion (measured with a Borg scale).

Active treatment group

Inspiratory and expiratory muscle training at a non-therapeutic intensity OTHER

The sham-control group will receive the same training protocol as the active treatment group but with a low (10% of PImax and PEmax) and stable non-therapeutic intensity.

Sham-controlled group

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 8 years;
• Respiratory muscle weakness (PImax ≤80 cmH2O (31));
• Maintenance dose (≥2 months) Spinraza® or (≥2 months) Risdiplam or no treatment;
• Given oral and written informed consent when ≥18 years old and additional informed consent by the parents or legal representative if the participant is \<16 years old.

You may not qualify if:

• Inability to perform respiratory and/or lung-function testing;
• Inability to understand Dutch or English;
• A history of pneumothorax or symptomatic low cardiac output syndrome;
• Treatment period \< 2 months of Spinraza® or Risdiplam

Sponsors & Collaborators

• UMC Utrecht: lead
• Princess Beatrix Muscle Foundation: collaborator

Study Sites (1)

University Medical Center Utrecht

Utrecht, 3508AB, Netherlands

Location

Related Publications (24)

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  PMID: 36959618 DERIVED

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

Inhalation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Erik Hulzebos, Dr

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The lung function analyst is blinded for treatment allocation. A data analyst will design and sign the data analysis plan in advance. The data will be analyzed according to the analysis plan by a physiotherapist who is not blinded for treatment allocation. The physiotherapists who will perform the two-weekly telephone calls are not blinded for treatment allocation. Patients will know that there are two treatment groups, and they are informed that it is not yet known which treatment is most effective.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical exercise physiologist, Child Development and Exercise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands

Model Details: In the first four months of the study, the active treatment group will receive inspiratory muscle training starting at a therapeutic intensity of 30% of maximum inspiratory mouth pressure (PImax) and expiratory muscle training starting at a therapeutic intensity of 30% of maximum expiratory mouth pressure (PEmax). The sham-control group will receive the same training protocol but with a low (10% of PImax and PEmax) non-therapeutic intensity. After four months, the sham-control group will also be provided with a supervised RMT at a therapeutic intensity of 30% of PImax and PEmax.

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: November 30, 2022
• Study Start: February 2, 2021
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: November 30, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)