Dyspnea in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder

NCT04972565 | Completed

• 1 other identifier: 20-6346
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypermobile EDS (hEDS); Hypermobility Syndrome

Keywords

Hypermobile Ehlers Danlos Syndrome; Hypermobility Spectrum Disorder; Dyspnea; Inspiratory Muscle Training; Exercise

Outcome Measures

Primary Outcomes (1)

• Maximal Inspiratory Pressure

  Maximal inspiratory pressure will be evaluated using standard methods in the pulmonary function laboratory, with the highest value (cm H2O) taken within 10 percent of the other readings as per American Thoracic Society recommendations.

  Change from baseline at 8 weeks

Secondary Outcomes (33)

• Maximal Expiratory Pressure

  Change from baseline at 8 weeks

• Respiratory Muscle Endurance

  Change from baseline at 4 weeks and 8 weeks

• Inspiratory Muscle Training Workload

  Through study completion, an average of 8 weeks

• Inspiratory Muscle Training Load

  Through study completion, an average of 8 weeks

• Inspiratory Muscle Training Mean Power

  Through study completion, an average of 8 weeks

Other Outcomes (5)

• Electrocardiogram

  Baseline

• Chest X-Ray

  Baseline

• Body Mass Index

  Change from baseline at 4 weeks and 8 weeks

Study Arms (2)

Usual Care plus Inspiratory Muscle Training (IMT)

EXPERIMENTAL

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.

Behavioral: Usual Care plus Inspiratory Muscle Training (IMT)

Usual Care

NO INTERVENTION

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

Interventions

Usual Care plus Inspiratory Muscle Training (IMT) BEHAVIORAL

Participants will receive usual care and will also be provided with a personalized prescription for an IMT program for 8 weeks. Participants will perform two daily IMT sessions of 30 breaths (\< 5 minutes/session), 5 days per week in their home environment. IMT intensity will be progressed weekly by 5-10% of the baseline maximal inspiratory pressure if the Borg Dyspnea score is \< 7.

Usual Care plus Inspiratory Muscle Training (IMT)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (7)

• Reychler G, Liistro G, Pierard GE, Hermanns-Le T, Manicourt D. Inspiratory muscle strength training improves lung function in patients with the hypermobile Ehlers-Danlos syndrome: A randomized controlled trial. Am J Med Genet A. 2019 Mar;179(3):356-364. doi: 10.1002/ajmg.a.61016. Epub 2018 Dec 20.

  PMID: 30569502 BACKGROUND

• Hakim AJ, Grahame R. Non-musculoskeletal symptoms in joint hypermobility syndrome. Indirect evidence for autonomic dysfunction? Rheumatology (Oxford). 2004 Sep;43(9):1194-5. doi: 10.1093/rheumatology/keh279. No abstract available.

  PMID: 15317957 BACKGROUND

• Ayres JG, Pope FM, Reidy JF, Clark TJ. Abnormalities of the lungs and thoracic cage in the Ehlers-Danlos syndrome. Thorax. 1985 Apr;40(4):300-5. doi: 10.1136/thx.40.4.300.

  PMID: 4023980 BACKGROUND

• Morgan AW, Pearson SB, Davies S, Gooi HC, Bird HA. Asthma and airways collapse in two heritable disorders of connective tissue. Ann Rheum Dis. 2007 Oct;66(10):1369-73. doi: 10.1136/ard.2006.062224. Epub 2007 Apr 5.

  PMID: 17412739 BACKGROUND

• Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the joint hypermobility syndrome. Am J Med. 2003 Jul;115(1):33-40. doi: 10.1016/s0002-9343(03)00235-3.

  PMID: 12867232 BACKGROUND

• Chatzoudis D, Kelly TJ, Lancaster J, Jones TM. Upper airway obstruction in a patient with Ehlers-Danlos syndrome. Ann R Coll Surg Engl. 2015 Apr;97(3):e50-1. doi: 10.1308/003588414X14055925061793.

  PMID: 26263828 BACKGROUND

• Rozenberg D, Al Kaabi N, Camacho Perez E, Nourouzpour S, Lopez-Hernandez L, McGillis L, Goligher E, Reid WD, Chow CW, Ryan CM, Kumbhare D, Huszti E, Champagne K, Raj S, Mak S, Santa Mina D, Clarke H, Mittal N. Evaluation and Management of Dyspnea in Hypermobile Ehlers-Danlos Syndrome and Generalized Hypermobility Spectrum Disorder: Protocol for a Pilot and Feasibility Randomized Controlled Trial. JMIR Res Protoc. 2023 Mar 20;12:e44832. doi: 10.2196/44832.

  PMID: 36939815 DERIVED

MeSH Terms

Conditions

Ehlers-Danlos syndrome type 3; Dyspnea; Motor Activity

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• Dmitry Rozenberg, MD, PhD

  University Health Network/University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Hypermobile EDS and HSD participants will be randomized to an inspiratory muscle training group versus usual care. Baseline measures will be compared to 17 age and sex-matched healthy controls.

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: July 22, 2021
• Study Start: August 16, 2021
• Primary Completion: March 21, 2025
• Study Completion: March 21, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)