An interventional study of Upright Exercise and Supine Exercise in Hepatopulmonary Syndrome, sponsored by Unity Health Toronto. Recruiting at 1 site in Canada. Per ClinicalTrials.gov, last updated 2023-05-10.
Sponsored by Unity Health Toronto · Not applicable, Interventional, and Supportive care
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.
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.
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Exclusion Criteria:
Participants will perform upright exercise on a cycle ergometer. The opposite test will be completed within 4 weeks.
Diagnostic Test: Upright Exercise
Participants will perform supine exercise on a cycle ergometer. The opposite test will be completed within 4 weeks.
Diagnostic Test: Supine Exercise
Exercise is generally performed in the upright position.
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.
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).
Time frame: 12 months
Isotime Oxygen Uptake (VO2)
Comparing oxygen uptake in the supine and upright position.
Time frame: 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.
Time frame: 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.
Time frame: 12 months
Work Rate
Constant work rate / resistance at which the cycle ergometer was set.
Time frame: 12 months
Arterial Oxygen Saturation
The saturation of oxygen in the arteries.
Time frame: 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.
Time frame: 12 months
Reason for Stopping Exercise
Reason due to which tLIM was reached and exercise was stopped.
Time frame: 12 months
Minute Ventilation (VE)
The quantity of air expired out of the lungs per minute.
Time frame: 12 months
Heart Rate
The number of heart beats per minute, also known as pulse.
Time frame: 12 months
VCO2
Carbon dioxide output per unit of time.
Time frame: 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).
Time frame: 12 months
HR over VO2
The change of heart rate to the volume of oxygen consumed in respiration over a period of time.
Time frame: 12 months
VE over time
The change of VE during the entire duration of the exercise.
Time frame: 12 months
VO2/ HR over time
The change of oxygen pulse during the entire duration of the exercise.
Time frame: 12 months
Heart rate over time
The change of heart rate during the entire duration of the exercise.
Time frame: 12 months
Cardiac output
The volume of the blood pumped by the heart through the circulatory system in a minute.
Time frame: 12 months
Change in inspiratory capacity
The difference of the maximum volume of air that can be inspired following a normal, quiet expiration
Time frame: 12 months
VE max
Maximum minute ventilation
Time frame: 12 months
End tidal CO2 over time
The point at the end of exhalation when the CO2 reaches its highest concentration.
Time frame: 12 months
Plan to share: No
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Hepatopulmonary Syndrome
Unity Health Toronto