Dyspnea in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder

University Health Network, Toronto

Status: Completed

Conditions: Hypermobility Syndrome; Hypermobile EDS (hEDS)

Treatments: Behavioral: Usual Care plus Inspiratory Muscle Training (IMT)

Study type: Interventional

Funder types: Other

Identifiers

NCT04972565

20-6346

Details and patient eligibility

About

Individuals with hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD) often experience dyspnea. Inspiratory Muscle Training (IMT) has been shown to improve dyspnea and respiratory muscle function; however, the impact of IMT in combination with whole-body exercise training on respiratory muscle strength, dyspnea, and daily function remains unknown. The objectives of this research are i) to evaluate dyspnea, respiratory muscle strength and function, ventilatory parameters, and health-related quality of life (HRQL) in individuals with hEDS and HSD compared to healthy age and sex-matched controls, ii) to explore the contributors to dyspnea during exercise with a specific focus on respiratory muscle structure and function in hEDS and HSD patients and healthy controls, and iii) to assess whether the combination of IMT and whole-body exercise training will be more effective than whole-body exercise training alone in improving participant outcomes in hEDS and HSD participants. It is hypothesized that i) hEDS and HSD participants will have lower respiratory muscle strength, higher peripheral airway resistance, lower HRQL, and higher anxiety and depression levels compared to healthy controls, ii) the contributors to increased exercise induced dyspnea will include decreased respiratory muscle strength, increased airway resistance, and greater prefrontal cortical neural activity, and iii) the combination of IMT and whole-body exercise training will be superior to whole-body training alone for improving dyspnea, respiratory muscle strength and endurance, aerobic capacity, HRQL, anxiety, and depression.

Full description

Thirty-four hEDS and HSD participants will be recruited from the University Health Network (Toronto, Canada). Participants will have baseline evaluations of dyspnea, pulmonary function tests (i.e., oscillometry, spirometry, and lung volumes), respiratory muscle structure and function (i.e., diaphragm ultrasound and respiratory muscle strength), HRQL, anxiety and depression. Symptom limited cardiopulmonary exercise testing will be utilized to quantify exertional dyspnea using the 10-item Borg dyspnea scale, 18-point qualitative dyspnea assessment scale, peak oxygen uptake (peak VO2), and assessment of dynamic ventilatory parameters. Neural activity in the pre-frontal cortex will be measured during cardiopulmonary exercise testing via functional near-infrared spectroscopy. These baseline measures will be compared to 17 age and sex-matched healthy controls. After baseline assessments, hEDS and HSD participants will be randomized to one of the following groups: i) Usual Care plus IMT: 8 weeks of whole-body exercises (standard care provided to hEDS and HSD patients at the University Health Network) plus a concurrent IMT intervention 5 times per week); ii) Usual Care: 8 weeks of whole-body exercises (as outlined above). After four and eight weeks, participants will have repeat assessments as described below.

Exertional dyspnea is a prevalent and troublesome symptom experienced by individuals living with hEDS and HSD. This study will provide a better understanding of the underlying contributors of dyspnea in hEDS and HSD patients, with a focus on respiratory muscle structure and function, prefrontal cortical neural activity, and ventilatory parameters, both at rest and with exertion.

Enrollment: 34 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult participants (≥ 18 years of age)
• New referral to the GoodHope Exercise and Rehabilitation (GEAR) Program at the University Health Network
• Diagnosis of hEDS based on the 2017 diagnostic criteria or diagnosis of HSD (defined as generalized joint hypermobility, chronic pain, and systemic findings to suspect connective tissue underpinnings) with clinical verification by the EDS medical team

Exclusion criteria

• Genetic testing confirming the diagnosis of another type of EDS (i.e., vascular EDS, classical EDS)
• Any contraindication to exercise testing (i.e., unstable cardiac disease). Presence of cardiac pacemaker/implantable defibrillator or structural cardiac abnormalities on echocardiogram
• Recent respiratory infection (< 1 month) or known diagnosis of obstructive (i.e., asthma, chronic obstructive pulmonary disease) or restrictive parenchymal lung disease
• History of pneumothorax, otitis media (fluid behind the ear drum), or rupture of tympanic membranes given risk with IMT
• Recent participation in formal exercise training or IMT program (within the last 3 months)
• Persistent symptoms or difficulty tolerating IMT (i.e., breathing difficulties and/or chest pain)
• Diagnosis of severe autonomic dysfunction or postural orthostatic tachycardia syndrome limiting daily physical activity or exercise
• Neuromuscular disease (i.e., myositis, diaphragm paralysis) that may interfere with IMT
• Insufficient English fluency to provide informed consent or ability to follow study protocols
• Self-reported pregnancy
• Inability to connect to the internet

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

34 participants in 2 patient groups

Usual Care plus Inspiratory Muscle Training (IMT)

Experimental group

Description:

Participants will attend the standard of care rehabilitation program offered to hEDS and HSD patients at the University Health Network. The program consists of i) an individualized home-based rehabilitation and exercise program (twelve weeks of aerobic, neuromotor, and resistance-based exercises), ii) a self-management education intervention, and iii) a community resource engagement plan. Furthermore, patients attend four on-site sessions (a baseline assessment and three follow-up visits). Participants in this group will also be provided with a personalized prescription for an IMT program for eight weeks to be performed in the home environment (two daily IMT sessions of 30 breaths, five days per week). Participants will be virtually supervised by the study team weekly with any adverse events closely monitored. Participants will receive instructions and feedback on how to optimize their home training efforts with direct observation of their IMT practice.

Treatment:

Behavioral: Usual Care plus Inspiratory Muscle Training (IMT)

Usual Care

No Intervention group

Description:

Participants will participate in the standard of care rehabilitation program offered to hEDS and HSD patients at the University Health Network.