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

NCT02024386 | Completed Phase 4 Results DMC

• 1 other identifier: Pro00049150
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypertension, Pulmonary; Altitude Sickness

Keywords

Guanylate Cyclase; Pulmonary Edema of Mountaineers; Mountaineering; Performance-Enhancing Substances; Athletic Performance

Outcome Measures

Primary Outcomes (1)

• Mean Pulmonary Artery Pressure

  Subject pulmonary artery pressures will be continuously monitored during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).

  At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test

Secondary Outcomes (5)

• Mean Radial Arterial Pressure

  At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test

• Mean Arterial Oxygen Saturation (SaO2)

  At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test

• Mean Ventilation Rate

  At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test

• Mean Work Rate at Exhaustion

  At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test

• Cardiac Output

  At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test

Study Arms (3)

Riociguat 0.5 mg

EXPERIMENTAL

Riociguat 0.5 mg tablets, one-time oral dose of 0.5 mg

Drug: Riociguat

Riociguat 1.0 mg

EXPERIMENTAL

Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg

Drug: Riociguat

Control arm

NO INTERVENTION

No drug

Interventions

Riociguat DRUG

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.

Also known as: Adempas, NDA 204819

Riociguat 0.5 mg; Riociguat 1.0 mg

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and females
• Non-smoking
• Non-pregnant females
• Ages 18 - 40 years old

You may not qualify if:

• 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).

Sponsors & Collaborators

• Richard Moon: lead

Study Sites (1)

Duke Center for Hyperbaric Medicine and Environmental Physiology, Trent Drive, Building CR2, Room 0584, Box 3823,

Durham, North Carolina, 27710, United States

Location

Related Publications (31)

• Torre-Bueno JR, Wagner PD, Saltzman HA, Gale GE, Moon RE. Diffusion limitation in normal humans during exercise at sea level and simulated altitude. J Appl Physiol (1985). 1985 Mar;58(3):989-95. doi: 10.1152/jappl.1985.58.3.989.

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MeSH Terms

Conditions

Hypertension, Pulmonary; Altitude Sickness; Pulmonary edema of mountaineers

Interventions

riociguat

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Respiration Disorders

Results Point of Contact

• Title: Richard Moon, MD
• Organization: Duke University School of Medicine

richard.moon@duke.edu

919-684-6726

Study Officials

• Richard E Moon, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director, Duke Center for Hyperbaric Medicine and Environmental Physiology, Professor of Anesthesiology, Professor of Medicine

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: December 31, 2013
• Study Start: January 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 12, 2017
• Results First Posted: April 12, 2017

Record last verified: 2017-03

Locations

US (1)