Hepatopulmonary SyndromeNCT04004104
Supine Exercise in Hepatopulmonary Syndrome Patients With Orthodeoxia
A study testing Upright Exercise and Supine Exercise in people with Hepatopulmonary Syndrome, run by Unity Health Toronto at 1 site in Canada.
Trial summary
Hepatopulmonary syndrome (HPS) is a rare condition that presents in about a quarter of patients with liver cirrhosis. In addition, a small subset of these HPS patients also have orthodeoxia, defined as a drop in oxygen levels when they are sitting up (upright), as opposed to lying flat (supine). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hepatopulmonary Syndrome
- What is being tested?
- Upright Exercise and Supine Exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- 24 Jul 2019to 31 Aug 2024
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of moderate HPS (defined by liver disease, hypoxemia [PaO2 < 80 mmHg and AaDo2 (alveolar-arterial PO2 difference) ≥ 15 mmHg or ≥ 20 mmHg if age > 64 years] and IPVD (intrapulmonary vasodilatations) as shown by contrast echocardiography])
- Presence of orthodeoxia (PaO2 decrease by >4 mmHg when patient moves from supine to upright position).
Who cannot join
- Pulmonary hypertension (echocardiographic estimated right ventricular systolic pressure >/=50 mmHg and/or right heart catheterization mean pulmonary artery pressure >25 mmHg with pulmonary capillary wedge pressure </= 15 mmHg);
- Significant obstructive ventilatory impairment (FEV1/FVC ratio < 0.65) (FEV=forced expiratory volume in 1 second; FVC=forced vital capacity)
- Known significant coronary artery disease;
- Significant neurologic, orthopedic or rheumatological disorders preventing the use of a cycle ergometer;
- Other absolute contraindications to submaximal tests (uncontrolled cardiac arrhythmia with hemodynamic compromise, symptomatic severe aortic stenosis, decompensated heart failure and acute cardiopulmonary illness);
- Moderate or severe ascites.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Samir Gupta, MD, MSc, (416) 864-6060 ext. 2252, guptas@smh.ca
Samir Gupta, MD, MSc
About this study
Official title: Design and Rationale for a Randomized Controlled Crossover Trial of Supine Versus Upright Exercise in Patients With Hepatopulmonary Syndrome and Orthodeoxia
Hepatopulmonary syndrome (HPS) is a rare condition that presents in about a quarter of patients with liver cirrhosis. In addition, a small subset of these HPS patients also have orthodeoxia, defined as a drop in oxygen levels when they are sitting up (upright), as opposed to lying flat (supine). At present, there is little known about this condition. Patients diagnosed with HPS and orthodeoxia experience reduced ability to exercise, especially when upright. While standard cardiopulmonary exercise is routinely performed in the sitting position, there are machines that enable candidates to exercise in the supine position. This is especially relevant in patients with severe HPS, with clinically significant orthodeoxia, where conventional upright exercise is difficult. Currently there is a gap in the literature regarding the efficacy of supine exercise compared to upright exercise in these patients. Due to their improvement in dyspnea when lying supine, it is predicted that these patients will be able to exercise for a greater length of time and have increased exercise capacity, which can be projected to improve outcomes pre- and post-transplant.
Overall, HPS patients tend to experience hypoxemia and exercise limitation. Exercise limitation impacts quality of life, incidence and severity of comorbid conditions, and in those who are liver transplant candidates, low exercise tolerance deleteriously impacts transplant outcomes. Accordingly, a strategy that enables patients to exercise more often and/or for longer periods would offer direct benefits to patients with HPS, and if employed as part of an exercise program, could also improve exercise capacity, and thus, liver transplant outcomes.
The purpose of this study is to investigate the effect of supine, compared to upright position on exercise in patients with HPS and orthodeoxia. We hypothesize that these patients will be able to exercise for longer in the supine compared to the upright position, given improved oxygen levels when supine.
Read the detailed description
This is a 1 year randomized crossover controlled trial study of the effect of supine exercise position (intervention arm) compared to the upright exercise position (control arm) within 4 weeks. This is a single-center study conducted at St. Michael's Hospital, Toronto, Ontario.
The exercise will be performed at a constant work rate, individualized for each participant. Peak work rate will be calculated using results from the most recent room air 6-minute walk test (6MWT), within the past 6 months. The equation used to estimate peak work rate is: Peak Work Rate = 0.168 x 6MWD (m) - 4.085 (ref Kozu Respirology 2010). The individualized constant work rate will be set at 70-80% of this estimated peak work rate.
The main stopping criterion will be the point at which, after standardized encouragement, the subject is unable to continue because of symptoms (i.e. patient does not wish to continue or cannot maintain a minimum peddling frequency of 40 rpm for ≥ 10 seconds). This is defined as the "tolerable limit" (tLIM). Additional safety-related stopping criteria will include: the appearance of life-threatening arrhythmias, a drop in systolic blood pressure by ≥ 10 mm Hg from baseline, or a desaturation below a set point for ≥ 30 s. The set saturation point will be chosen individually for each patient, as the lower of: 80% or the lowest saturation seen on room air 6MWT.
Exercise tests in each position, for each subject, will be standardized with respect to the proper seat adjustment relative to leg length and pedaling cadence (50-60 rpm). Inspiratory capacity will be measured before and after the exercise maneuver.
The cycle ergometer resistance will be set to the pre-determined constant work rate, as described above. There will be continuous monitoring of saturation, ECG, gas exchange, blood pressure, and subjective dyspnea/leg fatigue (Borg scale), with standardized verbal encouragement throughout. Participants will be asked to bring running shoes and comfortable exercise clothes, ensure that they have eaten before the test, to take all usual medications, and to avoid major exercise for 24 hours before the test.
- Conditions
- Hepatopulmonary Syndrome
- Being tested
- Upright Exercise, Supine Exercise
- Keywords
- Supine Exercise, Orthodeoxia
- Medical subject headings
- Hepatopulmonary Syndrome, Platypnea Orthodeoxia Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Upright ExerciseDiagnostic test
Exercise is generally performed in the upright position.
Supine ExerciseDiagnostic test
Since HPS patients with orthodeoxia experience an improvement in their symptoms and oxygen levels when supine, the intervention will involve them performing exercise in the supine position.
| Study group | Role | What they receive |
|---|---|---|
| Control - Upright Exercise | Active comparator | Participants will perform upright exercise on a cycle ergometer. The opposite test will be completed within 4 weeks. Receives: Diagnostic Test: Upright Exercise |
| Intervention - Supine Exercise | Experimental | Participants will perform supine exercise on a cycle ergometer. The opposite test will be completed within 4 weeks. Receives: Diagnostic Test: Supine Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stopping time (tLIM)
The main stopping criterion will be the point at which, after standardized encouragement, the subject is unable to continue because of symptoms [defined as the "tolerable limit" (tLIM)]. Additional safety-related stopping criteria will include: the appearance of complex ventricular arrhythmias, intraventricular and/or atrioventricular conduction disorders, bradyarrhythmias, or a desaturation below a set point for ≥ 10 s. The set saturation point will be chosen individually for each patient, as the lower of: 80%, or the nadir desaturation seen on room air six-minute walk test (6MWT).
Measured: 12 months
Secondary outcomes (19)
Isotime Oxygen Uptake (VO2)
Comparing oxygen uptake in the supine and upright position.
Measured: 12 months
Dyspnea
Patient's subjective measure of shortness of breath using Borg scale. This scale ranges from 0 to 10, with 0 being no shortness of breath to 10 being maximal shortness of breath.
Measured: 12 months
Leg Fatigue
Patient's subjective measure of leg fatigue using Borg scale. This scale ranges from 0 to 10, with 0 being no leg fatigue at all to 10 being maximal leg fatigue.
Measured: 12 months
Work Rate
Constant work rate / resistance at which the cycle ergometer was set.
Measured: 12 months
Arterial Oxygen Saturation
The saturation of oxygen in the arteries.
Measured: 12 months
Change in Inspiratory Capacity
Measuring volume of air that can be maximally inspired after normal tidal breaths and comparing between supine and upright.
Measured: 12 months
Reason for Stopping Exercise
Reason due to which tLIM was reached and exercise was stopped.
Measured: 12 months
Minute Ventilation (VE)
The quantity of air expired out of the lungs per minute.
Measured: 12 months
Heart Rate
The number of heart beats per minute, also known as pulse.
Measured: 12 months
VCO2
Carbon dioxide output per unit of time.
Measured: 12 months
VCO2 over VO2
The volume of carbon dioxide produced to the volume of oxygen consumed in respiration over a period of time, also known as respiratory quotient (RQ).
Measured: 12 months
HR over VO2
The change of heart rate to the volume of oxygen consumed in respiration over a period of time.
Measured: 12 months
VE over time
The change of VE during the entire duration of the exercise.
Measured: 12 months
VO2/ HR over time
The change of oxygen pulse during the entire duration of the exercise.
Measured: 12 months
Heart rate over time
The change of heart rate during the entire duration of the exercise.
Measured: 12 months
Cardiac output
The volume of the blood pumped by the heart through the circulatory system in a minute.
Measured: 12 months
Change in inspiratory capacity
The difference of the maximum volume of air that can be inspired following a normal, quiet expiration
Measured: 12 months
VE max
Maximum minute ventilation
Measured: 12 months
End tidal CO2 over time
The point at the end of exhalation when the CO2 reaches its highest concentration.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2019
- Study start24 Jul 2019
- Primary completion1 Dec 2023 (estimated)
- Study completion31 Aug 2024 (estimated)
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 Hepatopulmonary SyndromeStudies of the same condition, open and under way.
- More trials run by Unity Health 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will be randomized (through a random-number generator, and with cancelled allocation) to start with either an upright exercise test (control arm) or a supine exercise test (intervention arm) on a bicycle ergometer, and then complete the alternate test within 4 weeks.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samir Gupta, MD, MSc, Principal investigator, Clinician-Scientist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04004104
- Sponsor's protocol ID
- 19-127
- Status last verified
- May 2023
- First submitted
- 27 Jun 2019
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Parikh H, Lui E, Faughnan ME, Al-Hesayen A, Segovia S, Gupta S. Supine vs upright exercise in patients with hepatopulmonary syndrome and orthodeoxia: study protocol for a randomized controlled crossover trial. Trials. 2021 Oct 9;22(1):683. doi: 10.1186/s13063-021-05633-7.
PubMed 34625098
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Design and Rationale for a Randomized Controlled Crossover Trial of Supine Versus Upright Exercise in Patients With Hepatopulmonary Syndrome and Orthodeoxia
- ClinicalTrials.gov ID
- NCT04004104
- Acronym / sponsor ID
- 19-127
- Conditions
- Hepatopulmonary Syndrome
- Keywords
- Supine Exercise, Orthodeoxia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- 24 Jul 2019 (actual)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 31 Aug 2024 (estimated)
- First posted
- 1 Jul 2019 (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.
Hepatopulmonary syndrome (HPS) is a rare condition that presents in about a quarter of patients with liver cirrhosis. In addition, a small subset of these HPS patients also have orthodeoxia, defined as a drop in oxygen levels when they are sitting up (upright), as opposed to lying flat (supine). At present, there is little known about this condition. Patients diagnosed with HPS and orthodeoxia experience reduced ability to exercise, especially when upright. While standard cardiopulmonary exercise is routinely performed in the sitting position, there are machines that enable candidates to exercise in the supine position. This is especially relevant in patients with severe HPS, with clinically significant orthodeoxia, where conventional upright exercise is difficult. Currently there is a gap in the literature regarding the efficacy of supine exercise compared to upright exercise in these patients. Due to their improvement in dyspnea when lying supine, it is predicted that these patients will be able to exercise for a greater length of time and have increased exercise capacity, which can be projected to improve outcomes pre- and post-transplant.
Overall, HPS patients tend to experience hypoxemia and exercise limitation. Exercise limitation impacts quality of life, incidence and severity of comorbid conditions, and in those who are liver transplant candidates, low exercise tolerance deleteriously impacts transplant outcomes. Accordingly, a strategy that enables patients to exercise more often and/or for longer periods would offer direct benefits to patients with HPS, and if employed as part of an exercise program, could also improve exercise capacity, and thus, liver transplant outcomes.
The purpose of this study is to investigate the effect of supine, compared to upright position on exercise in patients with HPS and orthodeoxia. We hypothesize that these patients will be able to exercise for longer in the supine compared to the upright position, given improved oxygen levels when supine.
Detailed description
This is a 1 year randomized crossover controlled trial study of the effect of supine exercise position (intervention arm) compared to the upright exercise position (control arm) within 4 weeks. This is a single-center study conducted at St. Michael's Hospital, Toronto, Ontario.
The exercise will be performed at a constant work rate, individualized for each participant. Peak work rate will be calculated using results from the most recent room air 6-minute walk test (6MWT), within the past 6 months. The equation used to estimate peak work rate is: Peak Work Rate = 0.168 x 6MWD (m) - 4.085 (ref Kozu Respirology 2010). The individualized constant work rate will be set at 70-80% of this estimated peak work rate.
The main stopping criterion will be the point at which, after standardized encouragement, the subject is unable to continue because of symptoms (i.e. patient does not wish to continue or cannot maintain a minimum peddling frequency of 40 rpm for ≥ 10 seconds). This is defined as the "tolerable limit" (tLIM). Additional safety-related stopping criteria will include: the appearance of life-threatening arrhythmias, a drop in systolic blood pressure by ≥ 10 mm Hg from baseline, or a desaturation below a set point for ≥ 30 s. The set saturation point will be chosen individually for each patient, as the lower of: 80% or the lowest saturation seen on room air 6MWT.
Exercise tests in each position, for each subject, will be standardized with respect to the proper seat adjustment relative to leg length and pedaling cadence (50-60 rpm). Inspiratory capacity will be measured before and after the exercise maneuver.
The cycle ergometer resistance will be set to the pre-determined constant work rate, as described above. There will be continuous monitoring of saturation, ECG, gas exchange, blood pressure, and subjective dyspnea/leg fatigue (Borg scale), with standardized verbal encouragement throughout. Participants will be asked to bring running shoes and comfortable exercise clothes, ensure that they have eaten before the test, to take all usual medications, and to avoid major exercise for 24 hours before the test.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized (through a random-number generator, and with cancelled allocation) to start with either an upright exercise test (control arm) or a supine exercise test (intervention arm) on a bicycle ergometer, and then complete the alternate test within 4 weeks.
| Arm | Type | Receives |
|---|---|---|
| Control - Upright Exercise | Active comparator | Diagnostic Test: Upright ExerciseParticipants will perform upright exercise on a cycle ergometer. The opposite test will be completed within 4 weeks. |
| Intervention - Supine Exercise | Experimental | Diagnostic Test: Supine ExerciseParticipants will perform supine exercise on a cycle ergometer. The opposite test will be completed within 4 weeks. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosis of moderate HPS (defined by liver disease, hypoxemia [PaO2 < 80 mmHg and AaDo2 (alveolar-arterial PO2 difference) ≥ 15 mmHg or ≥ 20 mmHg if age > 64 years] and IPVD (intrapulmonary vasodilatations) as shown by contrast echocardiography])
- Presence of orthodeoxia (PaO2 decrease by >4 mmHg when patient moves from supine to upright position).
Key exclusion criteria (6 listed)
- Pulmonary hypertension (echocardiographic estimated right ventricular systolic pressure >/=50 mmHg and/or right heart catheterization mean pulmonary artery pressure >25 mmHg with pulmonary capillary wedge pressure </= 15 mmHg);
- Significant obstructive ventilatory impairment (FEV1/FVC ratio < 0.65) (FEV=forced expiratory volume in 1 second; FVC=forced vital capacity)
- Known significant coronary artery disease;
- Significant neurologic, orthopedic or rheumatological disorders preventing the use of a cycle ergometer;
- Other absolute contraindications to submaximal tests (uncontrolled cardiac arrhythmia with hemodynamic compromise, symptomatic severe aortic stenosis, decompensated heart failure and acute cardiopulmonary illness);
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 |
|---|---|---|
| Upright ExerciseExercise is generally performed in the upright position. | Diagnostic test | Control - Upright Exercise |
| Supine ExerciseSince HPS patients with orthodeoxia experience an improvement in their symptoms and oxygen levels when supine, the intervention will involve them performing exercise in the supine position. | Diagnostic test | Intervention - Supine Exercise |
Primary outcome
Stopping time (tLIM)
Time frame: 12 months
The main stopping criterion will be the point at which, after standardized encouragement, the subject is unable to continue because of symptoms [defined as the "tolerable limit" (tLIM)]. Additional safety-related stopping criteria will include: the appearance of complex ventricular arrhythmias, intraventricular and/or atrioventricular conduction disorders, bradyarrhythmias, or a desaturation below a set point for ≥ 10 s. The set saturation point will be chosen individually for each patient, as the lower of: 80%, or the nadir desaturation seen on room air six-minute walk test (6MWT).
19 secondary outcomes
Isotime Oxygen Uptake (VO2)
Time frame: 12 months
Dyspnea
Time frame: 12 months
Leg Fatigue
Time frame: 12 months
Work Rate
Time frame: 12 months
Arterial Oxygen Saturation
Time frame: 12 months
Change in Inspiratory Capacity
Time frame: 12 months
Reason for Stopping Exercise
Time frame: 12 months
Minute Ventilation (VE)
Time frame: 12 months
Heart Rate
Time frame: 12 months
VCO2
Time frame: 12 months
VCO2 over VO2
Time frame: 12 months
HR over VO2
Time frame: 12 months
VE over time
Time frame: 12 months
VO2/ HR over time
Time frame: 12 months
Heart rate over time
Time frame: 12 months
Cardiac output
Time frame: 12 months
Change in inspiratory capacity
Time frame: 12 months
VE max
Time frame: 12 months
End tidal CO2 over time
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Derived from this study: PubMed 34625098Parikh H, Lui E, Faughnan ME, Al-Hesayen A, Segovia S, Gupta S. Supine vs upright exercise in patients with hepatopulmonary syndrome and orthodeoxia: study protocol for a randomized controlled crossover trial. Trials. 2021 Oct 9;22(1):683. doi: 10.1186/s13063-021-05633-7.
- Peak work rate estimated from 6-minute walk distance.Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Hepatopulmonary Syndrome
Enrolling by invitationObservational study
International Registry of Congenital Portosystemic Shunt (IRCPSS)
Congenital Portosystemic Shunt, CPSS (Congenital Portosystemic Shunt)
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.
Samir Gupta, MD, MSc principal investigator
Clinician-Scientist
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Upright Exercise and Supine Exercise in people with Hepatopulmonary Syndrome, run by Unity Health 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 2 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 10 May 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Samir Gupta, MD, MSc ((416) 864-6060 ext. 2252, GuptaS@smh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stopping time (tLIM) (time frame: 12 months). 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 NCT04004104, 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 10 May 2023.