Efficacy Study of Riociguat and Its Effects on Exercise Performance and Pulmonary Artery Pressure at High Altitude
Condition: Hypertension, Pulmonary; Altitude Sickness
MeSH terms: Hypertension, Pulmonary; Altitude Sickness
Intervention: Riociguat
Intervention description: After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. Riociguat will be administered at the 90-minute mark of this rest period.
Intervention MeSH terms: Riociguat
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Guanylate Cyclase; Pulmonary Edema of Mountaineers; Mountaineering; Performance-Enhancing Substances; Athletic Performance

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.
    

Eligibility 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).