Ventricular Dysfunction, RightNCT05272514
Impact of Hypoxia on Resting and Exertional Right Ventricular Performance
An observational study of Ventricular Dysfunction, Right and Hypoxia, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The purpose of this study is to better understand how hypoxia (low oxygen) affects resting and exertional right ventricular function in healthy individuals. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Ventricular Dysfunction, Right, Hypoxia
- What is being tested?
- Hypoxia
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Apr 2022to 15 Dec 2022
- 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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: 10 healthy men and women
Who may be able to join
- Age 18 - 60
- For women, premenopausal status
Who cannot join
- Active cardiovascular or pulmonary disease (e.g. hypertension, coronary artery disease, cardiomyopathy, arrhythmia, valvular abnormalities, diabetes, peripheral vascular disease, tobacco use, chronic obstructive pulmonary disease, asthma, interstitial lung disease, restrictive lung disease, or pulmonary hypertension)
- Use of cardiac- or pulmonary-related medications
- Prior history of high altitude pulmonary edema or high altitude cerebral edema
- Body mass index < 18.5 or > 30
- Anemia
- Iron deficiency
Show all 13Show fewer
- Iron supplementation (oral or intravenous) in the preceding 60 days
- Systemic anticoagulation or aspirin use that cannot be temporarily held for the study
- Pregnancy
- Non-cardiopulmonary disorders that adversely influence exercise ability (e.g. arthritis or peripheral vascular disease)
- Dedicated athletic training (defined here as spending >9 hours per week in vigorous physical activity [≥6 mets])
- Regular high-altitude exercise (defined here as engaging in vigorous physical activity [≥1 hour at ≥6 mets] at ≥8,000 ft for >2 days per week over the preceding 4 weeks)
- Residence at ≥8,000 ft for 3 or more consecutive nights in the preceding 30 days
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
Official title: Impact of Hypoxia on Resting and Exertional Right Ventricular Performance - A PILOT STUDY
The purpose of this study is to better understand how hypoxia (low oxygen) affects resting and exertional right ventricular function in healthy individuals.
Read the detailed description
The right ventricle plays a critical role in exercise. As workload increases with exercise, the right ventricle augments contractility and lusitropy (diastolic relaxation) to accommodate increased venous return (preload) and pulmonary arterial pressure (afterload). Using gold-standard pressure-volume analysis, the investigators have shown that impairments in right ventricular function limit functional capacity among individuals with cardiovascular disease, heart failure and pulmonary hypertension. In addition, the investigators have characterized right ventricular function during exercise in the healthy heart using these techniques. Hypoxia increases pulmonary arterial pressure via hypoxic pulmonary vasoconstriction. By increasing right ventricular afterload, hypoxia may compromise exercise capacity. However, data regarding the impact of hypoxia on right ventricular performance are lacking.
This is a human physiology study of resting and exertional right ventricular function under control (normoxic) and hypoxic conditions. The investigators will use pressure-volume analysis in conjunction with Swan-Ganz catheterization and echocardiography to assess right ventricular performance in healthy individuals at rest and during exercise in normoxia and hypoxia. The study protocol consists of three visits.
- Visit 1: Non-invasive symptom-limited cardiopulmonary exercise test under normoxic conditions (FiO2= 0.21).
- Visit 2: Non-invasive symptom-limited cardiopulmonary exercise test under hypoxic conditions (FiO2=0.12).
- Visit 3: Invasive resting and exertional hemodynamic assessment under normoxic and hypoxic conditions
In Visits 1 and 2, heart rate/rhythm, oxygen saturation, blood pressure, gas exchange parameters (oxygen uptake [VO2], carbon dioxide production [VCO2], and minute ventilation), and rated perceived exertion will be monitored. Cardiopulmonary exercise testing (CPET) will be performed on an upright cycle ergometer with workload starting at 0 Watts and increasing every 2 minutes until volitional exhaustion with maximum workload at 8-12 minutes. The order of Visits 1 and 2 will be randomized to reduce the potential for bias from a learning/ordering effect.
In Visit 3, the same non-invasive measurements will be obtained. Additionally, right heart catheterization with Swan-Ganz catheter and conductance catheter placement will be performed. This will provide gold-standard hemodynamic and pressure-volume loop analysis to measure outcomes of right ventricular contractility, lusitropy (diastolic relaxation), afterload, and ventricular-arterial coupling. First, participants will complete submaximal exercise at FiO2=0.21. Submaximal exercise will include 5 minutes at 50% of baseline maximal oxygen uptake (VO2max achieved during Visit 1). After 20 minutes' rest, hemodynamic measurements will be obtained at rest at FiO2 0.21, 0.17, 0.15 and 0.12 to characterize the impact of progressive hypoxia on resting right ventricular hemodynamics. Participants will then perform submaximal exercise (50% VO2 max from hypoxic baseline at Visit 2) at FiO2 0.12. Thereafter, participants will complete a symptom-limited CPET at FiO2 0.12 with monitoring of invasive hemodynamics.
- Conditions
- Ventricular Dysfunction, Right, Hypoxia
- Being tested
- Hypoxia
- Medical subject headings
- Ventricular Dysfunction, Right, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HypoxiaOther
Individuals will be exposed to varying levels of hypoxia according to the protocol detailed above.
| Study group | Role | What they receive |
|---|---|---|
| Healthy individuals | 10 healthy individuals will be recruited. Receives: Other: Hypoxia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Right ventricular contractility measured by conductance catheter
End-systolic elastance (Ees) in mmHg/mL
Measured: Up to 1 hour
Right ventricular lusitropy (diastolic function) measured by conductance catheter
Minimum dp/dt in mmHg/sec
Measured: Up to 1 hour
Secondary outcomes (7)
Right ventricular stroke work measured by conductance catheter
Area of pressure-volume loop
Measured: Up to 1 hour
Mean pulmonary artery pressure measured by right heart catheterization
In mmHg
Measured: Up to 1 hour
Cardiac output derived from right heart catheterization
In L/min, calculated by Fick equation
Measured: Up to 1 hour
Workload
Workloads attained with submaximal and maximal exercise testing
Measured: Up to 1 hour
Maximal oxygen uptake
VO2max achieved in maximal exercise testing
Measured: Up to 1 hour
Plasma acylcarnitine 10:0 measured by peripheral venous metabolomics (ultra-high performance liquid chromatography coupled to mass spectrometry)
Relative ion count
Measured: Up to 1 hour
Red blood cell acylcarnitine 10:0 measured by peripheral venous metabolomics (ultra-high performance liquid chromatography coupled to mass spectrometry)
Relative ion count
Measured: Up to 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2022
- Study start15 Apr 2022
- Primary completion30 Aug 2022
- Study completion15 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Ventricular Dysfunction, RightStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05272514
- Sponsor's protocol ID
- 21-4354
- Status last verified
- May 2023
- First submitted
- 8 Feb 2022
- Last updated
- 9 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Smith TG, Balanos GM, Croft QP, Talbot NP, Dorrington KL, Ratcliffe PJ, Robbins PA. The increase in pulmonary arterial pressure caused by hypoxia depends on iron status. J Physiol. 2008 Dec 15;586(24):5999-6005. doi: 10.1113/jphysiol.2008.160960. Epub 2008 Oct 27.
PubMed 18955380Smith TG, Talbot NP, Privat C, Rivera-Ch M, Nickol AH, Ratcliffe PJ, Dorrington KL, Leon-Velarde F, Robbins PA. Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA. 2009 Oct 7;302(13):1444-50. doi: 10.1001/jama.2009.1404.
PubMed 19809026Cornwell WK, Tran T, Cerbin L, Coe G, Muralidhar A, Hunter K, Altman N, Ambardekar AV, Tompkins C, Zipse M, Schulte M, O'Gean K, Ostertag M, Hoffman J, Pal JD, Lawley JS, Levine BD, Wolfel E, Kohrt WM, Buttrick P. New insights into resting and exertional right ventricular performance in the healthy heart through real-time pressure-volume analysis. J Physiol. 2020 Jul;598(13):2575-2587. doi: 10.1113/JP279759. Epub 2020 May 18.
PubMed 32347547Cornwell WK 3rd, Baggish AL, Bhatta YKD, Brosnan MJ, Dehnert C, Guseh JS, Hammer D, Levine BD, Parati G, Wolfel EE; American Heart Association Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; and Council on Arteriosclerosis, Thrombosis and Vascular Biology. Clinical Implications for Exercise at Altitude Among Individuals With Cardiovascular Disease: A Scientific Statement From the American Heart Association. J Am Heart Assoc. 2021 Oct 5;10(19):e023225. doi: 10.1161/JAHA.121.023225. Epub 2021 Sep 9.
PubMed 34496612Forbes LM, Bull TM, Lahm T, Sisson T, O'Gean K, Lawley JS, Hunter K, Levine BD, Lovering A, Roach RC, Subudhi AW, Cornwell WK 3rd. Right ventricular performance during acute hypoxic exercise. J Physiol. 2024 Nov;602(21):5523-5537. doi: 10.1113/JP284943. Epub 2024 Feb 26.
PubMed 38409819Forbes LM, Bull TM, Lahm T, Lawley JS, Hunter K, Levine BD, Lovering A, Roach RC, Subudhi AW, Cornwell WK 3rd. Right Ventricular Response to Acute Hypoxia among Healthy Humans. Am J Respir Crit Care Med. 2023 Aug 1;208(3):333-336. doi: 10.1164/rccm.202303-0599LE. No abstract available.
PubMed 37311248
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Hypoxia on Resting and Exertional Right Ventricular Performance - A PILOT STUDY
- ClinicalTrials.gov ID
- NCT05272514
- Acronym / sponsor ID
- 21-4354
- Conditions
- Ventricular Dysfunction, Right, Hypoxia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 15 Apr 2022 (actual)
- Primary completion
- 30 Aug 2022 (actual)
- Study completion
- 15 Dec 2022 (actual)
- First posted
- 9 Mar 2022 (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.
The purpose of this study is to better understand how hypoxia (low oxygen) affects resting and exertional right ventricular function in healthy individuals.
Detailed description
The right ventricle plays a critical role in exercise. As workload increases with exercise, the right ventricle augments contractility and lusitropy (diastolic relaxation) to accommodate increased venous return (preload) and pulmonary arterial pressure (afterload). Using gold-standard pressure-volume analysis, the investigators have shown that impairments in right ventricular function limit functional capacity among individuals with cardiovascular disease, heart failure and pulmonary hypertension. In addition, the investigators have characterized right ventricular function during exercise in the healthy heart using these techniques. Hypoxia increases pulmonary arterial pressure via hypoxic pulmonary vasoconstriction. By increasing right ventricular afterload, hypoxia may compromise exercise capacity. However, data regarding the impact of hypoxia on right ventricular performance are lacking.
This is a human physiology study of resting and exertional right ventricular function under control (normoxic) and hypoxic conditions. The investigators will use pressure-volume analysis in conjunction with Swan-Ganz catheterization and echocardiography to assess right ventricular performance in healthy individuals at rest and during exercise in normoxia and hypoxia. The study protocol consists of three visits.
- Visit 1: Non-invasive symptom-limited cardiopulmonary exercise test under normoxic conditions (FiO2= 0.21).
- Visit 2: Non-invasive symptom-limited cardiopulmonary exercise test under hypoxic conditions (FiO2=0.12).
- Visit 3: Invasive resting and exertional hemodynamic assessment under normoxic and hypoxic conditions
In Visits 1 and 2, heart rate/rhythm, oxygen saturation, blood pressure, gas exchange parameters (oxygen uptake [VO2], carbon dioxide production [VCO2], and minute ventilation), and rated perceived exertion will be monitored. Cardiopulmonary exercise testing (CPET) will be performed on an upright cycle ergometer with workload starting at 0 Watts and increasing every 2 minutes until volitional exhaustion with maximum workload at 8-12 minutes. The order of Visits 1 and 2 will be randomized to reduce the potential for bias from a learning/ordering effect.
In Visit 3, the same non-invasive measurements will be obtained. Additionally, right heart catheterization with Swan-Ganz catheter and conductance catheter placement will be performed. This will provide gold-standard hemodynamic and pressure-volume loop analysis to measure outcomes of right ventricular contractility, lusitropy (diastolic relaxation), afterload, and ventricular-arterial coupling. First, participants will complete submaximal exercise at FiO2=0.21. Submaximal exercise will include 5 minutes at 50% of baseline maximal oxygen uptake (VO2max achieved during Visit 1). After 20 minutes' rest, hemodynamic measurements will be obtained at rest at FiO2 0.21, 0.17, 0.15 and 0.12 to characterize the impact of progressive hypoxia on resting right ventricular hemodynamics. Participants will then perform submaximal exercise (50% VO2 max from hypoxic baseline at Visit 2) at FiO2 0.12. Thereafter, participants will complete a symptom-limited CPET at FiO2 0.12 with monitoring of invasive hemodynamics.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy individuals | – | Other: Hypoxia10 healthy individuals will be recruited. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- 10 healthy men and women
Key inclusion criteria (2 listed)
- Age 18 - 60
- For women, premenopausal status
Key exclusion criteria (13 listed)
- Active cardiovascular or pulmonary disease (e.g. hypertension, coronary artery disease, cardiomyopathy, arrhythmia, valvular abnormalities, diabetes, peripheral vascular disease, tobacco use, chronic obstructive pulmonary disease, asthma, interstitial lung disease, restrictive lung disease, or pulmonary hypertension)
- Use of cardiac- or pulmonary-related medications
- Prior history of high altitude pulmonary edema or high altitude cerebral edema
- Body mass index < 18.5 or > 30
- Anemia
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 |
|---|---|---|
| HypoxiaIndividuals will be exposed to varying levels of hypoxia according to the protocol detailed above. | Other | Healthy individuals |
Primary outcome
Right ventricular contractility measured by conductance catheter
Time frame: Up to 1 hour
End-systolic elastance (Ees) in mmHg/mL
Right ventricular lusitropy (diastolic function) measured by conductance catheter
Time frame: Up to 1 hour
Minimum dp/dt in mmHg/sec
7 secondary outcomes
Right ventricular stroke work measured by conductance catheter
Time frame: Up to 1 hour
Mean pulmonary artery pressure measured by right heart catheterization
Time frame: Up to 1 hour
Cardiac output derived from right heart catheterization
Time frame: Up to 1 hour
Workload
Time frame: Up to 1 hour
Maximal oxygen uptake
Time frame: Up to 1 hour
Plasma acylcarnitine 10:0 measured by peripheral venous metabolomics (ultra-high performance liquid chromatography coupled to mass spectrometry)
Time frame: Up to 1 hour
Red blood cell acylcarnitine 10:0 measured by peripheral venous metabolomics (ultra-high performance liquid chromatography coupled to mass spectrometry)
Time frame: Up to 1 hour
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 9 May 2023.
- Background: PubMed 18955380Smith TG, Balanos GM, Croft QP, Talbot NP, Dorrington KL, Ratcliffe PJ, Robbins PA. The increase in pulmonary arterial pressure caused by hypoxia depends on iron status. J Physiol. 2008 Dec 15;586(24):5999-6005. doi: 10.1113/jphysiol.2008.160960. Epub 2008 Oct 27.
- Background: PubMed 19809026Smith TG, Talbot NP, Privat C, Rivera-Ch M, Nickol AH, Ratcliffe PJ, Dorrington KL, Leon-Velarde F, Robbins PA. Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA. 2009 Oct 7;302(13):1444-50. doi: 10.1001/jama.2009.1404.
- Background: PubMed 32347547Cornwell WK, Tran T, Cerbin L, Coe G, Muralidhar A, Hunter K, Altman N, Ambardekar AV, Tompkins C, Zipse M, Schulte M, O'Gean K, Ostertag M, Hoffman J, Pal JD, Lawley JS, Levine BD, Wolfel E, Kohrt WM, Buttrick P. New insights into resting and exertional right ventricular performance in the healthy heart through real-time pressure-volume analysis. J Physiol. 2020 Jul;598(13):2575-2587. doi: 10.1113/JP279759. Epub 2020 May 18.
- Background: PubMed 34496612Cornwell WK 3rd, Baggish AL, Bhatta YKD, Brosnan MJ, Dehnert C, Guseh JS, Hammer D, Levine BD, Parati G, Wolfel EE; American Heart Association Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; and Council on Arteriosclerosis, Thrombosis and Vascular Biology. Clinical Implications for Exercise at Altitude Among Individuals With Cardiovascular Disease: A Scientific Statement From the American Heart Association. J Am Heart Assoc. 2021 Oct 5;10(19):e023225. doi: 10.1161/JAHA.121.023225. Epub 2021 Sep 9.
- Derived from this study: PubMed 38409819Forbes LM, Bull TM, Lahm T, Sisson T, O'Gean K, Lawley JS, Hunter K, Levine BD, Lovering A, Roach RC, Subudhi AW, Cornwell WK 3rd. Right ventricular performance during acute hypoxic exercise. J Physiol. 2024 Nov;602(21):5523-5537. doi: 10.1113/JP284943. Epub 2024 Feb 26.
- Derived from this study: PubMed 37311248Forbes LM, Bull TM, Lahm T, Lawley JS, Hunter K, Levine BD, Lovering A, Roach RC, Subudhi AW, Cornwell WK 3rd. Right Ventricular Response to Acute Hypoxia among Healthy Humans. Am J Respir Crit Care Med. 2023 Aug 1;208(3):333-336. doi: 10.1164/rccm.202303-0599LE. No abstract available.
- Individual participant dataSharing planned: No
Related trials for Ventricular Dysfunction, Right
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
RecruitingObservational study
dPmax for Predicting Right Ventricular Failure After Left Ventricular Assist Device Implantation
Ventricular Dysfunction, Right
RecruitingObservational study
Right Ventricular Function and Respiratory Acidosis After Cardiac Surgery
Respiratory Acidosis in ICU Patients, Right Ventricular (RV) Dysfunction
RecruitingPhase 2
Feasibility Trial for a Right Ventricular Failure Platform Trial
Pulmonary Hypertension, Right Ventricular Dysfunction
RecruitingObservational study
Pulmonary Embolism Registry From Short-Term Emergency to Long-Term Follow-Up and Surveillance
Venous Thromboembolism (VTE), Chronic Thromboembolic Pulmonary Hypertension
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.
The record lists no contact. Use the official record to reach the sponsor.
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 Ventricular Dysfunction, Right and Hypoxia, run by University of Colorado, Denver at 1 site in United States.
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 13 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 9 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 United States. 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?
Right ventricular contractility measured by conductance catheter (time frame: Up to 1 hour). 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 NCT05272514, which also lists 6 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 9 May 2023.