Blood Markers Predict Effect of Normobaric Hypoxia at Rest and During Exercise in Patients With Pulmonary Hypertension (HEXABM)

Hemodynamic Effects of Acute Normobaric Hypoxia During Exercise in Patients With Pulmonary Hypertension: Single-center Randomized Controlled Trial

To study the effect of acute normobaric hypoxia during exercise in patients with pulmonary hypertension on blood markers (serum markers of iron and red blood cell homeostasis and micro-RNAs known to be associated with PH).

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Other: Normobaric hypoxia (FiO2 15%); Other: Placebo-ambient air (FiO2 21%); Other: Normobaric hypoxia (FiO2 15%) under Sildenafil; Other: Placebo-ambient air (FiO2 21%) under Sildenafil

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • University Hospital of Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed consent as documented by signature (Appendix Informed Consent Form)
• PH class I (PAH) or IV (CTEPH) diagnosed according to guidelines: mean pulmonary artery pressure >20 mmHg, pulmonary vascular resistance ≥3 wood units, pulmonary arterial wedge pressure ≤15 mmHg during baseline measures at the diagnostic right-heart catheterization

Exclusion Criteria:

• resting partial pressure of oxygen <8 kilopascal at Zürich altitude on ambient air
• exposure to an altitude >1000 m for ≥3 nights during the last 2 weeks before the study
• inability to follow the procedures of the study
• patients who take nitrates
• other clinically significant concomitant end-stage disease (e.g., renal failure, hepatic dysfunction)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normobaric hypoxia (FiO2 15%); Inhalation of deoxygenated air through an altitude simulator ("Altitrainer"), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.	Other: Normobaric hypoxia (FiO2 15%); Inhalation of deoxygenated air through an altitude simulator ("Altitrainer"), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.
Sham Comparator: Placebo-ambient air (FiO2 21%); Inhalation of room air through an altitude simulator ("Altitrainer"), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.	Other: Placebo-ambient air (FiO2 21%); Inhalation of room air through an altitude simulator ("Altitrainer"), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.
Experimental: Normobaric hypoxia (FiO2 15%) under Sildenafil; Inhalation of deoxygenated air through an altitude simulator ("Altitrainer"), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.	Other: Normobaric hypoxia (FiO2 15%) under Sildenafil; Inhalation of deoxygenated air through an altitude simulator ("Altitrainer"), for approx. 1/2 hour given by a facemask, first at rest and then during exercise under Sildenafil.
Active Comparator: Placebo-ambient air (FiO2 21%) under Sildenafil; Inhalation of room air through an altitude simulator ("Altitrainer"), for approx. 1/2 hour given by a facemask, first at rest and then during exercise.	Other: Placebo-ambient air (FiO2 21%) under Sildenafil; Inhalation of room air through an altitude simulator ("Altitrainer"), for approx. 1/2 hour given by a facemask, first at rest and then during exercise under Sildenafil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum levels of ferritin	Analyis of serum levels of ferritin	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum levels of transferrin	Analyis of serum levels of transferrin	Baseline
Serum levels of total iron	Analysis of serum levels of total iron	Baseline
Serum levels of erythropoietin	Analysis of serum levels of erythropoietin	Baseline
Serum levels of Erythroferrone	Analysis of serum levels of erythroferrone	Baseline
Serum levels of hepcidin	Analysis of serum levels of hepcidin	Baseline
micro-RNA levels	Analysis of micro-RNA levels	Baseline

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Silvia Ulrich, Prof. Dr., UniversityHospital Zurich, Department of Pulmonology

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: December 20, 2020
• First Submitted That Met QC Criteria: January 14, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): June 6, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: exercise; hypoxia; blood markers
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Signs and Symptoms, Respiratory; Hypertension; Hypertension, Pulmonary; Hypoxia; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 2020-02163_A4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share individual participant data after publication of the manuscript. The decision about the platform is ongoing.
• IPD Sharing Time Frame: After publication of the manuscript

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No