Chronic Thromboembolic Pulmonary HypertensionNCT03786367
Dyspnea in Chronic Thromboembolic Pulmonary Hypertension
An observational study of Chronic Thromboembolic Pulmonary Hypertension, run by Dr. Denis O'Donnell at 1 site in Canada.
Trial summary
Pulmonary embolism, or clots blocking the blood vessels of the lungs, is a common clinical condition requiring treatment with blood thinners. In most patients, recovery is complete. A small proportion of patients, however, develop complications (high blood pressure in the lung circulation, i.e. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Chronic Thromboembolic Pulmonary Hypertension
- How many people
- 28 participants
- Where
- 1 siteCanada
- Study dates
- 1 Nov 2018to 1 Jan 2023
- Phase
- Observational
- 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects will include 20 clinically stable patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) recruited from the Pulmonary Hypertension outpatient clinics at Hotel Dieu Hospital, Kingston, Ontario. Healthy Control data will be from previous studies (no additional testing required in this group).
Who may be able to join
- clinically stable as defined by stable hemodynamic status, optimized medical treatment, no changes in medication dosage or frequency of administration with no hospital admissions in the preceding 6 weeks
- male or female ≥40 years of age
- non-smoker
- moderate-to-severe chronic activity-related dyspnea as defined by a modified Medical Research Council (MRC) dyspnea scale ≥2, or Baseline Dyspnea Index focal score ≤ 6
- ability to perform all study procedures and provide/sign informed consent.
Who cannot join
- women of childbearing age who are pregnant or trying to become pregnant
- active cardiopulmonary disease or other comorbidities that could contribute to dyspnea and exercise limitation
- important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s)
- use of daytime oxygen or exercise-induced O2 desaturation to < 80% on room air
- body mass index (BMI) <18.5 or ≥35.0 kg/m2
- other causes of significant pulmonary hypertension: pulmonary arterial hypertension, left heart disease, chronic pulmonary disease including, obstructive sleep apnea or pulmonary hypertension of unclear or multifactorial mechanism
- systemic connective tissue disease
Trial locations and contacts
1 site in 1 country.
Canada1 site
Respiratory Investigation Unit, Kingston General Hospital
Kingston, Ontario, K7L 2V7
About this study
Official title: Mechanisms of Exertional Dyspnea in Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Pulmonary embolism, or clots blocking the blood vessels of the lungs, is a common clinical condition requiring treatment with blood thinners. In most patients, recovery is complete. A small proportion of patients, however, develop complications (high blood pressure in the lung circulation, i.e. pulmonary hypertension). Persisting breathlessness during activity is a common symptom in many of these patients and leads to a reduced ability to engage in daily physical activity. The reason for this activity-related breathlessness remains uncertain and is the main question of the proposed study. Using new sophisticated technology, the investigators will determine the root causes of perceived breathing difficulty. The investigators will test the idea that breathlessness is fundamentally the result of increased drive to breathe from control centers in the brain. The investigators will measure drive to breathe by measuring the electrical activity descending from the brain to the main muscle of breathing - the diaphragm. The investigators will discover if the increased drive to breathe is due to accumulation of carbon dioxide in the blood as a result of poor blood perfusion of areas of the lung due to the effects of blockage by clots. The investigators also will investigate whether weakness and fatigue of the muscles of breathing, as a result of the high breathing demands that are present in patients with blood clots in the lungs, contribute to breathlessness. With this information it is hopeful that better treatment options will be developed to relieve this distressing symptom.
Read the detailed description
Rationale: In patients with pulmonary embolism, most assessments of the burden of blood clots and possible related complications, currently rely on chest imaging and heart ultrasound. While these tests are useful in charting the course of the disease, they offer little about how the function of the heart and lungs is altered by the disease or the cause of common symptoms such as breathlessness during exercise. To better understand the reasons for persistent activity- related breathlessness in patients with a history of clots to the lungs, the investigators will undertake detailed assessment of breathlessness using validated scales and questionnaires during standardized exercise testing. At the same time the investigators will also measure a broad range of physiological tests that will indirectly measure how much blood perfusion of the lungs is reduced, how much the drive to breathe is increased, and whether there is additional strain and weakness of the muscles of breathing, particularly the diaphragm. This will allow the investigators to identify the main factors contributing to breathlessness in this population and will help to guide management. It is hoped that the development of simple new physiological markers or tests obtained during the stress of exercise can, in addition to conventional imaging, be used to monitor the course of the disease and response to treatment. In particular, the investigators hope that these new tests will help clinicians recognize at an early stage of the disease individuals more likely to develop progressive heart disease and breathing problems as a result of blood clots to the lungs.
Study design/methodology: This will be a single-centre, cross-sectional study observing the effect of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) on exertional dyspnea and physiological responses to a standardized exercise task. After giving written informed consent, participants will complete 2 visits, each conducted in the morning 2-7 days apart. Visit 1 (screening for eligibility): medical history, symptom evaluation, complete pulmonary function testing, a symptom-limited incremental exercise test for familiarization of dyspnea assessments during exercise. Visits 2: pulmonary function testing (spirometry,) and a symptom-limited incremental exercise test to tolerance including detailed measurements of dyspnea (intensity, quality, affective dimensions), EMGdi and pressure-derived respiratory mechanical measurements. EMGdi will be used as an observational tool to measure inspiratory neural drive. An esophageal electrode-balloon catheter consisting of 5 electrode pairs will be inserted nasally and carefully positioned based on the strength of the EMGdi signal. EMGdi will be recorded continuously at rest and during exercise. The raw EMGdi signal will be sampled at 2000 Hz, band-pass filtered and converted to a root mean square (RMS) using computer software (LabChart). Maximal EMGdi (EMGdi,max) will be measured during inspiratory capacity (IC) maneuvers. EMGdi/EMGdi,max will be used as an index of the inspiratory neural drive to the crural diaphragm. Esophageal (Pes) and gastric pressures (Pga) will be recorded continuously at a rate of 200 Hz (PowerLab) using balloons mounted on the electrode catheter. Transdiaphragmatic pressure (Pdi) will be recorded as the difference between Pga and Pes signals. The continuous flow signal from the Vmax229d system will be input into the PowerLab system for offline analysis. Pre- and post-exercise inspiratory sniffs will be performed to obtain maximum Pes (Pes,sn) and Pdi (Pdi,sn). IC maneuvers at rest and throughout exercise will be used to obtain dynamic peak inspiratory Pes (Pes,IC) and Pdi (Pdi,IC). Pre- and post-exercise FVC maneuvers will also performed to obtain dynamic peak expiratory Pes (Pes,FVC). Respiratory mechanics will be analyzed as previously described (see reference). Vital signs will be monitored throughout exercise. Subjects will avoid caffeine, heavy meals, alcohol and major physical exertion prior to visits.
- Keywords
- Dyspnea, Exertional Dyspnea, Pulmonary Hypertension, Exercise
- Medical subject headings
- Dyspnea, Hypertension, Pulmonary, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| CTEPH | Clinically stable patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) recruited from the Pulmonary Hypertension outpatient clinics at Hotel Dieu Hospital, Kingston, Ontario. | |
| Control | Age and sex-matched healthy control data collected as part of previous studies will be used as historic controls for this study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise test
EMGdi will be used as an index of inspiratory neural drive. Assessments will be compared at a standardized time (at rest, during isotime and end-exercise) during incremental cycle ergometer exercise test.
Measured: Conducted at visit 2, 2-7 days after screening visit
Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle exercise test
The 10-point Borg scale ranges from 0 "nothing at all" to 10 "maximal/extremely strong" and will be used to rate the intensity of dyspnea during exercise: a decrease in this rating signifies an improvement. Dyspnea intensity will be assessed at a standardized time (every minute) during incremental cycle ergometer exercise test.
Measured: Conducted at visit 2, 2-7 days after screening visit
Secondary outcomes (5)
Inspiratory Capacity at a standardized time during cycle exercise test
Exercise measurements of inspiratory capacity will be compared at a standardized time (at rest, during isotime and end-exercise) during incremental cycle ergometer exercise test.
Measured: Conducted at visit 2, 2-7 days after screening visit
Ventilation at a standardized time during cycle exercise test
Exercise measurements of ventilation will be compared at a standardized time (at rest, during isotime and end-exercise) during incremental cycle ergometer exercise test.
Measured: Conducted at visit 2, 2-7 days after screening visit
Breathing frequency at a standardized time during cycle exercise test.
Exercise measurements of breathing frequency (respiratory rate) will be compared at a standardized time (at rest, during isotime and end-exercise) during incremental cycle ergometer exercise test.
Measured: Conducted at visit 2, 2-7 days after screening visit
Carbon dioxide output (VCO2) at a standardized time during cycle exercise test.
Exercise measurements of Carbon Dioxide output (VCO2) will be compared at a standardized time (at rest, during isotime and end-exercise) during incremental cycle ergometer exercise test.
Measured: Conducted at visit 2, 2-7 days after screening visit
Maximal oxygen uptake (VO2) at a standardized time during cycle exercise test.
Exercise measurements of Maximal oxygen uptake (VO2) will be compared at a standardized time (at rest, during isotime and end-exercise) during incremental cycle ergometer exercise test.
Measured: Conducted at visit 2, 2-7 days after screening visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2018
- Study start1 Nov 2018
- Primary completion30 Sep 2022
- Study completion1 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Thromboembolic Pulmonary HypertensionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Denis O'Donnell
- Sponsor type
- University, hospital or other
- Collaborators
- Queen's University
- Responsible party
- Sponsor-investigator, Dr. Denis O'Donnell, Queen's University
- Investigators
- Denis E O'Donnell, MD, Principal investigator, Respiratory Investigation Unit, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03786367
- Sponsor's protocol ID
- DMED-2208-18
- Status last verified
- Apr 2023
- First submitted
- 15 Nov 2018
- Last updated
- 13 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Faisal A, Alghamdi BJ, Ciavaglia CE, Elbehairy AF, Webb KA, Ora J, Neder JA, O'Donnell DE. Common Mechanisms of Dyspnea in Chronic Interstitial and Obstructive Lung Disorders. Am J Respir Crit Care Med. 2016 Feb 1;193(3):299-309. doi: 10.1164/rccm.201504-0841OC.
PubMed 26407036
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Exertional Dyspnea in Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
- ClinicalTrials.gov ID
- NCT03786367
- Acronym / sponsor ID
- DMED-2208-18
- Keywords
- Dyspnea, Exertional Dyspnea, Pulmonary Hypertension, Exercise
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Dr. Denis O'DonnellUniversity, hospital or other
- Collaborators
- Queen's University
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 30 Sep 2022 (actual)
- Study completion
- 1 Jan 2023 (actual)
- First posted
- 26 Dec 2018 (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.
Pulmonary embolism, or clots blocking the blood vessels of the lungs, is a common clinical condition requiring treatment with blood thinners. In most patients, recovery is complete. A small proportion of patients, however, develop complications (high blood pressure in the lung circulation, i.e. pulmonary hypertension). Persisting breathlessness during activity is a common symptom in many of these patients and leads to a reduced ability to engage in daily physical activity. The reason for this activity-related breathlessness remains uncertain and is the main question of the proposed study. Using new sophisticated technology, the investigators will determine the root causes of perceived breathing difficulty. The investigators will test the idea that breathlessness is fundamentally the result of increased drive to breathe from control centers in the brain. The investigators will measure drive to breathe by measuring the electrical activity descending from the brain to the main muscle of breathing - the diaphragm. The investigators will discover if the increased drive to breathe is due to accumulation of carbon dioxide in the blood as a result of poor blood perfusion of areas of the lung due to the effects of blockage by clots. The investigators also will investigate whether weakness and fatigue of the muscles of breathing, as a result of the high breathing demands that are present in patients with blood clots in the lungs, contribute to breathlessness. With this information it is hopeful that better treatment options will be developed to relieve this distressing symptom.
Detailed description
Rationale: In patients with pulmonary embolism, most assessments of the burden of blood clots and possible related complications, currently rely on chest imaging and heart ultrasound. While these tests are useful in charting the course of the disease, they offer little about how the function of the heart and lungs is altered by the disease or the cause of common symptoms such as breathlessness during exercise. To better understand the reasons for persistent activity- related breathlessness in patients with a history of clots to the lungs, the investigators will undertake detailed assessment of breathlessness using validated scales and questionnaires during standardized exercise testing. At the same time the investigators will also measure a broad range of physiological tests that will indirectly measure how much blood perfusion of the lungs is reduced, how much the drive to breathe is increased, and whether there is additional strain and weakness of the muscles of breathing, particularly the diaphragm. This will allow the investigators to identify the main factors contributing to breathlessness in this population and will help to guide management. It is hoped that the development of simple new physiological markers or tests obtained during the stress of exercise can, in addition to conventional imaging, be used to monitor the course of the disease and response to treatment. In particular, the investigators hope that these new tests will help clinicians recognize at an early stage of the disease individuals more likely to develop progressive heart disease and breathing problems as a result of blood clots to the lungs.
Study design/methodology: This will be a single-centre, cross-sectional study observing the effect of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) on exertional dyspnea and physiological responses to a standardized exercise task. After giving written informed consent, participants will complete 2 visits, each conducted in the morning 2-7 days apart. Visit 1 (screening for eligibility): medical history, symptom evaluation, complete pulmonary function testing, a symptom-limited incremental exercise test for familiarization of dyspnea assessments during exercise. Visits 2: pulmonary function testing (spirometry,) and a symptom-limited incremental exercise test to tolerance including detailed measurements of dyspnea (intensity, quality, affective dimensions), EMGdi and pressure-derived respiratory mechanical measurements. EMGdi will be used as an observational tool to measure inspiratory neural drive. An esophageal electrode-balloon catheter consisting of 5 electrode pairs will be inserted nasally and carefully positioned based on the strength of the EMGdi signal. EMGdi will be recorded continuously at rest and during exercise. The raw EMGdi signal will be sampled at 2000 Hz, band-pass filtered and converted to a root mean square (RMS) using computer software (LabChart). Maximal EMGdi (EMGdi,max) will be measured during inspiratory capacity (IC) maneuvers. EMGdi/EMGdi,max will be used as an index of the inspiratory neural drive to the crural diaphragm. Esophageal (Pes) and gastric pressures (Pga) will be recorded continuously at a rate of 200 Hz (PowerLab) using balloons mounted on the electrode catheter. Transdiaphragmatic pressure (Pdi) will be recorded as the difference between Pga and Pes signals. The continuous flow signal from the Vmax229d system will be input into the PowerLab system for offline analysis. Pre- and post-exercise inspiratory sniffs will be performed to obtain maximum Pes (Pes,sn) and Pdi (Pdi,sn). IC maneuvers at rest and throughout exercise will be used to obtain dynamic peak inspiratory Pes (Pes,IC) and Pdi (Pdi,IC). Pre- and post-exercise FVC maneuvers will also performed to obtain dynamic peak expiratory Pes (Pes,FVC). Respiratory mechanics will be analyzed as previously described (see reference). Vital signs will be monitored throughout exercise. Subjects will avoid caffeine, heavy meals, alcohol and major physical exertion prior to visits.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CTEPH | – | –Clinically stable patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) recruited from the Pulmonary Hypertension outpatient clinics at Hotel Dieu Hospital, Kingston, Ontario. |
| Control | – | –Age and sex-matched healthy control data collected as part of previous studies will be used as historic controls for this study. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects will include 20 clinically stable patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) recruited from the Pulmonary Hypertension outpatient clinics at Hotel Dieu Hospital, Kingston, Ontario. Healthy Control data will be from previous studies (no additional testing required in this group).
Key inclusion criteria (5 listed)
- clinically stable as defined by stable hemodynamic status, optimized medical treatment, no changes in medication dosage or frequency of administration with no hospital admissions in the preceding 6 weeks
- male or female ≥40 years of age
- non-smoker
- moderate-to-severe chronic activity-related dyspnea as defined by a modified Medical Research Council (MRC) dyspnea scale ≥2, or Baseline Dyspnea Index focal score ≤ 6
- ability to perform all study procedures and provide/sign informed consent.
Key exclusion criteria (7 listed)
- women of childbearing age who are pregnant or trying to become pregnant
- active cardiopulmonary disease or other comorbidities that could contribute to dyspnea and exercise limitation
- important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s)
- use of daytime oxygen or exercise-induced O2 desaturation to < 80% on room air
- body mass index (BMI) <18.5 or ≥35.0 kg/m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise test
Time frame: Conducted at visit 2, 2-7 days after screening visit
EMGdi will be used as an index of inspiratory neural drive. Assessments will be compared at a standardized time (at rest, during isotime and end-exercise) during incremental cycle ergometer exercise test.
Dyspnea intensity measured by the 10-point Borg Scale at a standardized time during cycle exercise test
Time frame: Conducted at visit 2, 2-7 days after screening visit
The 10-point Borg scale ranges from 0 "nothing at all" to 10 "maximal/extremely strong" and will be used to rate the intensity of dyspnea during exercise: a decrease in this rating signifies an improvement. Dyspnea intensity will be assessed at a standardized time (every minute) during incremental cycle ergometer exercise test.
5 secondary outcomes
Inspiratory Capacity at a standardized time during cycle exercise test
Time frame: Conducted at visit 2, 2-7 days after screening visit
Ventilation at a standardized time during cycle exercise test
Time frame: Conducted at visit 2, 2-7 days after screening visit
Breathing frequency at a standardized time during cycle exercise test.
Time frame: Conducted at visit 2, 2-7 days after screening visit
Carbon dioxide output (VCO2) at a standardized time during cycle exercise test.
Time frame: Conducted at visit 2, 2-7 days after screening visit
Maximal oxygen uptake (VO2) at a standardized time during cycle exercise test.
Time frame: Conducted at visit 2, 2-7 days after screening visit
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 13 Apr 2023.
- Background: PubMed 26407036Faisal A, Alghamdi BJ, Ciavaglia CE, Elbehairy AF, Webb KA, Ora J, Neder JA, O'Donnell DE. Common Mechanisms of Dyspnea in Chronic Interstitial and Obstructive Lung Disorders. Am J Respir Crit Care Med. 2016 Feb 1;193(3):299-309. doi: 10.1164/rccm.201504-0841OC.
- 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.
Denis E O'Donnell, MD principal investigator
Respiratory Investigation Unit, Queen's University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Thromboembolic Pulmonary Hypertension, run by Dr. Denis O'Donnell 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 5 inclusion and 7 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 13 Apr 2023. 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?
Diaphragm electromyography (EMGdi) at a standardized time during cycle exercise test (time frame: Conducted at visit 2, 2-7 days after screening visit). The study lists 2 primary outcomes in all. 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 NCT03786367, which also lists 1 linked publication.
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 13 Apr 2023.