Efficacy Study of Riociguat and Its Effects on Exercise Performance and Pulmonary Artery Pressure at High Altitude

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

During ascent to high altitude there is a physiologic response to hypoxia that results in an elevated pulmonary arterial pressure associated with decreased exercise performance, altitude-induced pulmonary hypertension, and high altitude pulmonary edema (HAPE). Riociguat is a novel agent from Bayer Pharmaceuticals that has already demonstrated effectiveness in the treatment of pulmonary hypertension, and it may prove to be beneficial in cases of altitude-induced pulmonary hypertension or HAPE. This research study, composed of 20 healthy volunteers ages 18-40 years, will attempt to mimic the decreased oxygen supply and elevated pulmonary artery pressures found in conditions of high altitude, allowing observation of the effects of riociguat and exercise on pulmonary arterial pressure, arterial oxygenation, and exercise performance. Prior to entering the hypobaric chamber, subjects will have radial arterial lines and pulmonary artery catheters placed to obtain arterial and pulmonary artery pressure measurements. Subjects will then enter the hypobaric chamber and perform exercise tolerance tests at a simulated altitude of 15,000 feet on an electrically braked ergometer (exercise bike) before and after administration of riociguat. If, after administration of riociguat and exposure to a simulated altitude of 15,000 feet, the exercise performance is improved and observed pulmonary artery pressures are lower than those measurements seen prior to administration of riociguat, this could lead to development of a prophylactic and/or treatment strategy for HAPE and high-altitude pulmonary hypertension. Statistical analysis will compare the variables of pulmonary artery pressure, radial arterial pressure, ventilation rate, cardiac output, PaO2, and work rate at exhaustion before and after administration of the drug riociguat. The investigator's hypothesis is that riociguat will decrease pulmonary artery pressure and improve gas exchange and exercise performance at altitude.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Richard Moon
• Treatments: Riociguat

Criteria

Inclusion Criteria:

• Healthy males and females

• Non-smoking

• Non-pregnant females

• Ages 18 - 40 years old

Exclusion Criteria:

• Serious pulmonary or cardiovascular comorbidities

• Pregnant women

• VO2max < 35 mL/kg per minute

• Sickle cell trait or disease

• Smokers

• Lung disease

• Hypertension

• Cardiac disease and left bundle branch block

• Taking nitrates, nitric oxide donors (such as amyl nitrite), and phosphodiesterase (PDE) inhibitors (including specific PDE-5 inhibitors, such as sildenafil, tadalafil, or vardenafil, or non-specific PDE inhibitors, such as dipyridamole or theophylline).