Skip to main content
OpenTrials
Completed

NCT Number: NCT02760121

AZ, MZ, and the Pulmonary System Response to Hypoxia

The purpose of this proposal is to compare the physiological effects of acetazolamide (AZ) and methazolamide (MZ) on the control of breathing and hypoxic pulmonary vasoconstriction. The first objective is to assess the effects of AZ and MZ on the control of breathing in normoxia and hypoxia. To achieve this the ventilatory interaction between oxygen and carbon dioxide will be measured and effects compared between placebo, AZ, and MZ conditions. In addition, the isocapnic and poikilocapnic hypoxic ventilatory response and hypercapnic ventilatory response will be measured with each drug. The second objective is to assess the effects of AZ and MZ on the control of the pulmonary vasculature during hypoxia. Pulmonary pressure and cardiac output will be measured during 60 minutes of poikilocapnic hypoxia.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Altitude Sickness Cardiovascular Diseases Hypertension Hypertension, Pulmonary Lung Diseases Respiration Disorders Respiratory Tract Diseases Vascular Diseases

Age range

18 year–40 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 4

Primary location

University of British Columbia

Kelowna, British Columbia, V1V 1V7, Canada

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 18-40 years of age
  • regularly physically active
  • male

Exclusion criteria

  • ex-smokers
  • pulmonary function <80% of predicted
  • contraindications to carbonic anhydrase inhibitors (eg. severe or absolute glaucoma, adrenocortical insufficiency, hepatic insufficiency, renal insufficiency, sulfa allergy or an electrolyte imbalance such as hyperchloremic acidosis)
  • Obese (BMI>30Kg/m2)
  • diuretic medication use
  • blood thinner use
  • anti-platelet drug use.

Treatment and study plan

Acetazolamide

Drug

Methazolamide

Drug

Placebo

Drug

Primary outcomes

  1. Change in ventilation

    Time frame: Baseline and 60 minutes of poikilocapnic hypoxia

    To quantify the isocapnic hypoxic ventilatory response, the hypercapnic ventilatory response, and the hypercapnic hypoxic ventilatory response, ventilation will be measured throughout controlled changes in end-tidal gas levels. Each protocol will consist of 90s steps in end-tidal oxygen partial pressure from baseline through 65, 57, and 47 mmHg. For hypercapnic hypoxia, the end-tidal partial pressure for carbon dioxide will be increased from baseline to +6 mmHg for 7 minutes before reducing the end-tidal partial pressure of oxygen as above. The poikilocapnic hypoxic ventilatory response will be determined by measuring the change in ventilation from baseline throughout 60 minutes of poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)

  2. Change in pulmonary artery pressure

    Time frame: Baseline and 60 minutes of poikilocapnic hypoxia

    Pulmonary artery systolic pressure (PASP) will be derived using the modified Bernoulli equation and the regurgitant velocity across the tricuspid valve. Estimates of right atrial pressure will be evaluated based upon the collapsibility index of the inferior vena cave during a sniff test. The pulmonary artery pressure response will be measured during 60 minutes of exposure to poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)

Secondary outcomes

  1. Change in cerebral blood velocity

    Time frame: Baseline and 60 minutes

    To quantify the isocapnic hypoxic cerebral blood velocity response, the hypercapnic cerebral blood velocity response, and the hypercapnic hypoxic cerebral blood velocity response, cerebral blood velocity in the middle and posterior cerebral arteries will be measured throughout controlled changes in end-tidal gas levels. Each protocol will consist of 90s steps in end-tidal oxygen partial pressure from baseline through 65, 57, and 47 mmHg. For hypercapnic hypoxia, the end-tidal carbon dioxide partial pressure will be increased from baseline to +6 mmHg for 7 minutes before reducing the end-tidal oxygen partial pressure as above. The poikilocapnic hypoxic ventilatory response will be determined by measuring the change in ventilation from baseline throughout 60 minutes of poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)

Other outcomes

  1. change in arterial oxygen partial pressure

    Time frame: Baseline and 60 minutes

  2. Change in arterial carbon dioxide partial pressure

    Time frame: Baseline and 60 minutes

  3. Change in arterial pH

    Time frame: Baseline and 60 minutes

  4. Change in heart rate

    Time frame: Baseline and 60 minutes

  5. change in blood pressure

    Time frame: Baseline and 60 minutes

  6. change in end-tidal oxygen and carbon dioxide partial pressure

    Time frame: Baseline and 60 minutes

  7. Change in arterial oxygen saturation

    Time frame: Baseline and 60 minutes

  8. Change in cardiac output

    Time frame: Baseline and 60 minutes of poikilocapnic hypoxia

    Cardiac output will be determined using the aortic time integral velocity and the diameter of the aortic valve annulus. Data will be collected at baseline and throughout exposure to poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)

  9. Change in pulmonary venous blood velocity

    Time frame: Baseline and 60 minutes of poikilocapnic hypoxia

    Doppler ultrasound will be used to measure the velocity of blood draining from the pulmonary vein at baseline and throughout exposure to poikilocapnic hypoxia (fraction of inspired oxygen = 0.12)

  10. Hemoglobin

    Time frame: Baseline

  11. albumin

    Time frame: Baseline

  12. iron

    Time frame: Baseline

Sponsors and collaborators

Lead sponsor

University of British Columbia

Other

Registry information

Official study title

The Effect of Carbonic Anhydrase Inhibitors on the Pulmonary System Response to Hypoxia

Important dates

Study start
2016
Primary completion
2016
Study completion
2016
First posted
May 3, 2016
Registry last updated
Oct 19, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.