Supine Exercise in Hepatopulmonary Syndrome Patients With Orthodeoxia

NCT04004104 | Unknown

• 1 other identifier: 19-127
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Hepatopulmonary Syndrome

Keywords

Supine Exercise; Orthodeoxia

Outcome Measures

Primary Outcomes (1)

• 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).

  12 months

Secondary Outcomes (19)

• Isotime Oxygen Uptake (VO2)

  12 months

• Dyspnea

  12 months

• Leg Fatigue

  12 months

• Work Rate

  12 months

• Arterial Oxygen Saturation

  12 months

Study Arms (2)

Control - Upright Exercise

ACTIVE COMPARATOR

Participants will perform upright exercise on a cycle ergometer. The opposite test will be completed within 4 weeks.

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.

Diagnostic Test: Supine Exercise

Interventions

Upright Exercise DIAGNOSTIC_TEST

Exercise is generally performed in the upright position.

Control - Upright Exercise

Supine Exercise DIAGNOSTIC_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.

Intervention - Supine Exercise

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

Related Publications (1)

• 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.

  PMID: 34625098 DERIVED

Related Links

• Peak work rate estimated from 6-minute walk distance.

MeSH Terms

Conditions

Hepatopulmonary Syndrome; Platypnea Orthodeoxia Syndrome

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Dyspnea; Respiration Disorders; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Samir Gupta, MD, MSc

  Clinician-Scientist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samir Gupta, MD, MSc

CONTACT

(416) 864-6060; GuptaS@smh.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The assessor (different from the PI) will not be present when the two exercise tests are performed. Additionally, the results will not be labeled with the specific position of the exercise test. In this manner, the assessor will be blinded to the exercise position and this blinding will strengthen the validity of the research outcomes.
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: July 1, 2019
• Study Start: July 24, 2019
• Primary Completion: December 1, 2023
• Study Completion: August 31, 2024
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)