Hypermobile EDS (hEDS)NCT04972565
Dyspnea in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder
A study of Hypermobile EDS (hEDS) and Hypermobility Syndrome, run by University Health Network, Toronto at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypermobile EDS (hEDS), Hypermobility Syndrome
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteCanada
- Study dates
- 16 Aug 2021to 21 Mar 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 11Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation and Management of Dyspnea in Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorder (HSD)
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.
Read the detailed 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.
- Conditions
- Hypermobile EDS (hEDS), Hypermobility Syndrome
- Being tested
- Usual Care plus Inspiratory Muscle Training (IMT)
- Keywords
- Hypermobile Ehlers Danlos Syndrome, Hypermobility Spectrum Disorder, Dyspnea, Inspiratory Muscle Training, Exercise
- Medical subject headings
- Ehlers-Danlos syndrome type 3, Dyspnea, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Usual Care plus Inspiratory Muscle Training (IMT)Behavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline at 8 weeks
Secondary outcomes (33)
Maximal Expiratory Pressure
Maximal expiratory 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.
Measured: Change from baseline at 8 weeks
Respiratory Muscle Endurance
Respiratory muscle endurance (endurance time measured in seconds) will be assessed using a manual threshold loading device (Philips Threshold trainer).
Measured: Change from baseline at 4 weeks and 8 weeks
Inspiratory Muscle Training Workload
Total IMT workload per session (product of inspiratory muscle force and inhaled volume expressed in Joules) will be extracted from the IMT device in the experimental group.
Measured: Through study completion, an average of 8 weeks
Inspiratory Muscle Training Load
Inspiratory muscle training Load (cm H2O) will be abstracted from the IMT device in the experimental group.
Measured: Through study completion, an average of 8 weeks
Inspiratory Muscle Training Mean Power
Inspiratory muscle training mean power per breath (Watts) will be abstracted from the IMT device in the experimental group.
Measured: Through study completion, an average of 8 weeks
Inspiratory Muscle Training Mean Volume
Inspiratory muscle training mean volume per breath (Litres) will be abstracted from the IMT device in the experimental group.
Measured: Through study completion, an average of 8 weeks
Medical Research Council Dyspnea Scale
The Medical Research Council Dyspnea Scale will be used to assess the effect of breathlessness on daily activities. The scale comprises five statements that describe the range of respiratory dyspnea from none (Grade 1) to severe with difficulties performing self-care (Grade 5).
Measured: Change from baseline at 8 weeks
Borg Dyspnea Scale
The 10-point Borg Dyspnea Scale will be used throughout the study to adjust the intensity of inspiratory muscle training sessions The lowest score (0) corresponds to the sensation of normal breathing (absence of dyspnea) and the highest score (10) corresponds to the maximum possible sensation of dyspnea.
Measured: Through study completion, an average of 8 weeks
Borg Dyspnea Scale
The 10-point Borg Dyspnea Scale will be used during cardiopulmonary exercise testing to characterize degree of dyspnea. The lowest score (0) corresponds to the sensation of normal breathing (absence of dyspnea) and the highest score (10) corresponds to the maximum possible sensation of dyspnea.
Measured: Change from baseline at 8 weeks
Qualitative Assessment of Dyspnea
The 18-point Qualitative Dyspnea Scale will be ascertained at the end of cardiopulmonary exercise testing. Participants will be presented with a list of 18 descriptors characterizing their dyspnea and will be asked to rank the top three.
Measured: Change from baseline at 8 weeks
Qualitative Assessment of Dyspnea
The 18-point Qualitative Dyspnea Scale will be ascertained at the end of respiratory muscle endurance testing. Participants will be presented with a list of 18 descriptors characterizing their dyspnea and will be asked to rank the top three.
Measured: Change from baseline at 4 weeks and 8 weeks
Oscillometry
Oscillometry will be performed in the pulmonary function laboratory following the protocol from the European Respiratory Society.
Measured: Change from baseline at 8 weeks
Spirometry (Forced Vital Capacity)
Spirometry (forced vital capacity) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Measured: Change from baseline at 8 weeks
Spirometry (Forced Expiratory Volume in 1 Second)
Spirometry (forced expiratory volume in 1 second) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Measured: Change from baseline at 8 weeks
Lung Volumes (Total Lung Capacity)
Lung volumes (i.e., Total Lung Capacity) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Measured: Change from baseline at 8 weeks
Lung Volumes (Inspiratory Capacity)
Lung volumes (i.e., inspiratory capacity) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Measured: Change from baseline at 8 weeks
Lung Volumes (Residual Volume)
Lung volumes (i.e., Residual Volume) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Measured: Change from baseline at 8 weeks
Diaphragm Thickness
The right hemi-diaphragm thickness will be measured using a 13 megahertz ultrasound transducer.
Measured: Change from baseline at 8 weeks
Diaphragm Thickening Fraction
The right hemi-diaphragm thickening fraction will be measured using a 13 megahertz ultrasound transducer.
Measured: Change from baseline at 8 weeks
Peak Oxygen Uptake During Cardiopulmonary Exercise Testing
Cardiopulmonary exercise test-based assessment of peak oxygen uptake (VO2 peak) will be performed on a cycle ergometer.
Measured: Change from baseline at 8 weeks
Ventilatory Response During Cardiopulmonary Exercise Testing
Ventilatory response will be assessed during cardiopulmonary exercise testing (on a cycle ergometer) with exhaled gas measurements captured breath by breath.
Measured: Change from baseline at 8 weeks
Heart Rate Response During Cardiopulmonary Exercise Testing
Heart rate response will be assessed during cardiopulmonary exercise testing on a cycle ergometer.
Measured: Change from baseline at 8 weeks
Pre-frontal Cortical Neural Activity During Cardiopulmonary Exercise Testing
Oxygenated and total hemoglobin of the prefrontal cortex will be measured with Functional Near Infrared Spectroscopy during cardiopulmonary exercise testing.
Measured: Change from baseline at 8 weeks
Physical Activity Levels
Physical activity (daily steps) will be measured via a tracking device (Fitbit, San Francisco, USA) for a 7-day period.
Measured: Change from baseline at 4 weeks and 8 weeks
Leisure-Time Exercise
Leisure-time exercise will be measured via the 3-item Godin Leisure-Time Exercise Questionnaire - Leisure Score Index. The Leisure Score Index is used to rank individuals from the lowest to highest exercise levels: sedentary (score less than 14 units); moderately active (score of 14-23 units); and active (24 units or more).
Measured: Baseline
Health-Related Quality of Life
The Short-Form 36 Health Survey (SF-36) will be used to assess general health-related quality of life. The SF-36 consists of eight scaled scores (total score ranging from 0 to 100), with lower scores representing lower health-related quality of life.
Measured: Change from baseline at 8 weeks
Depression, Anxiety and Stress Scale
The Depression, Anxiety and Stress Scale (DASS-21) questionnaire has 21 items to assess mood (anxiety, depression, and stress). Each statement for the three domains is given a score of 0 (not applicable) to 3 (applicable most of the time) with scores categorized as follows: Normal, Mild, Moderate, Severe, and Extremely Severe.
Measured: Change from baseline at 8 weeks
Participant Study Recruitment
Recruitment-success percentage and reasons for participation/non-participation in the study will be collected.
Measured: Over the study period (8 weeks)
Participant Retention in the Study
Participant retention will be assessed by measuring participant follow-up with testing throughout the study period.
Measured: Over the study period (8 weeks)
Adherence to Inspiratory Muscle Training Load
Adherence to the IMT intervention will be tracked electronically via the IMT device (i.e., percentage of the maximal inspiratory pressure prescribed).
Measured: Over the intervention period (8 weeks)
Adherence to Inspiratory Muscle Training Days
Adherence to the IMT intervention will be tracked using a participant log to record the number of training days completed each week.
Measured: Over the intervention period (8 weeks)
Adverse Events During Inspiratory Muscle Training Practice (Safety and Tolerability)
Any adverse events (i.e. prolonged muscle soreness, pneumothorax) with IMT will be assessed throughout the study period.
Measured: Over the intervention period (8 weeks)
Participant Satisfaction with the IMT Intervention
A multiple-choice and free-form questionnaire assessing the participants' satisfaction with the IMT intervention will be completed by study participants.
Measured: Change from baseline at weeks 1, 4 and 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2021
- Study start16 Aug 2021
- Primary completion21 Mar 2025
- Study completion21 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hypermobile EDS (hEDS)Studies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dmitry Rozenberg, MD, PhD, Principal investigator, University Health Network/University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04972565
- Sponsor's protocol ID
- 20-6346
- Status last verified
- Mar 2025
- First submitted
- 25 Jun 2021
- Last updated
- 2 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30569502Hakim 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.
PubMed 15317957Ayres 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.
PubMed 4023980Morgan 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.
PubMed 17412739Gazit 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.
PubMed 12867232Chatzoudis 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.
PubMed 26263828Rozenberg 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.
PubMed 36939815
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation and Management of Dyspnea in Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorder (HSD)
- ClinicalTrials.gov ID
- NCT04972565
- Acronym / sponsor ID
- 20-6346
- Conditions
- Hypermobile EDS (hEDS), Hypermobility Syndrome
- Keywords
- Hypermobile Ehlers Danlos Syndrome, Hypermobility Spectrum Disorder, Dyspnea, Inspiratory Muscle Training, Exercise
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 16 Aug 2021 (actual)
- Primary completion
- 21 Mar 2025 (actual)
- Study completion
- 21 Mar 2025 (actual)
- First posted
- 22 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Usual Care plus Inspiratory Muscle Training (IMT) | Experimental | Behavioral: Usual Care plus Inspiratory Muscle Training (IMT)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. |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Usual Care plus Inspiratory Muscle Training (IMT)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. | Behavioural | Usual Care plus Inspiratory Muscle Training (IMT) |
Primary outcome
Maximal Inspiratory Pressure
Time frame: Change from baseline at 8 weeks
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.
33 secondary outcomes
Maximal Expiratory Pressure
Time frame: Change from baseline at 8 weeks
Respiratory Muscle Endurance
Time frame: Change from baseline at 4 weeks and 8 weeks
Inspiratory Muscle Training Workload
Time frame: Through study completion, an average of 8 weeks
Inspiratory Muscle Training Load
Time frame: Through study completion, an average of 8 weeks
Inspiratory Muscle Training Mean Power
Time frame: Through study completion, an average of 8 weeks
Inspiratory Muscle Training Mean Volume
Time frame: Through study completion, an average of 8 weeks
Medical Research Council Dyspnea Scale
Time frame: Change from baseline at 8 weeks
Borg Dyspnea Scale
Time frame: Through study completion, an average of 8 weeks
Borg Dyspnea Scale
Time frame: Change from baseline at 8 weeks
Qualitative Assessment of Dyspnea
Time frame: Change from baseline at 8 weeks
Qualitative Assessment of Dyspnea
Time frame: Change from baseline at 4 weeks and 8 weeks
Oscillometry
Time frame: Change from baseline at 8 weeks
Spirometry (Forced Vital Capacity)
Time frame: Change from baseline at 8 weeks
Spirometry (Forced Expiratory Volume in 1 Second)
Time frame: Change from baseline at 8 weeks
Lung Volumes (Total Lung Capacity)
Time frame: Change from baseline at 8 weeks
Lung Volumes (Inspiratory Capacity)
Time frame: Change from baseline at 8 weeks
Lung Volumes (Residual Volume)
Time frame: Change from baseline at 8 weeks
Diaphragm Thickness
Time frame: Change from baseline at 8 weeks
Diaphragm Thickening Fraction
Time frame: Change from baseline at 8 weeks
Peak Oxygen Uptake During Cardiopulmonary Exercise Testing
Time frame: Change from baseline at 8 weeks
Ventilatory Response During Cardiopulmonary Exercise Testing
Time frame: Change from baseline at 8 weeks
Heart Rate Response During Cardiopulmonary Exercise Testing
Time frame: Change from baseline at 8 weeks
Pre-frontal Cortical Neural Activity During Cardiopulmonary Exercise Testing
Time frame: Change from baseline at 8 weeks
Physical Activity Levels
Time frame: Change from baseline at 4 weeks and 8 weeks
Leisure-Time Exercise
Time frame: Baseline
Health-Related Quality of Life
Time frame: Change from baseline at 8 weeks
Depression, Anxiety and Stress Scale
Time frame: Change from baseline at 8 weeks
Participant Study Recruitment
Time frame: Over the study period (8 weeks)
Participant Retention in the Study
Time frame: Over the study period (8 weeks)
Adherence to Inspiratory Muscle Training Load
Time frame: Over the intervention period (8 weeks)
Adherence to Inspiratory Muscle Training Days
Time frame: Over the intervention period (8 weeks)
Adverse Events During Inspiratory Muscle Training Practice (Safety and Tolerability)
Time frame: Over the intervention period (8 weeks)
Participant Satisfaction with the IMT Intervention
Time frame: Change from baseline at weeks 1, 4 and 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Background: PubMed 30569502Reychler 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.
- Background: PubMed 15317957Hakim 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.
- Background: PubMed 4023980Ayres 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.
- Background: PubMed 17412739Morgan 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.
- Background: PubMed 12867232Gazit 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.
- Background: PubMed 26263828Chatzoudis 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.
- Derived from this study: PubMed 36939815Rozenberg 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dmitry Rozenberg, MD, PhD principal investigator
University Health Network/University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Hypermobile EDS (hEDS) and Hypermobility Syndrome, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal Inspiratory Pressure (time frame: Change from baseline at 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04972565, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2025.