AZ, MZ, and the Pulmonary System Response to Hypoxia

Hypertension, Pulmonary Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02760121
• Other study ID #: H16-00028
• Status: Completed
• Phase: Phase 4
• First received: April 20, 2016
• Last updated: October 18, 2016
• Start date: May 2016
• Est. completion date: August 2016

Study information

• Verified date: October 2016
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Altitude Sickness
• Hypertension, Pulmonary

Intervention

Drug:
• Acetazolamide

• Methazolamide

• Placebo

Locations

Country	Name	City	State
Canada	University of British Columbia	Kelowna	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	change in arterial oxygen partial pressure		Baseline and 60 minutes	No
Other	Change in arterial carbon dioxide partial pressure		Baseline and 60 minutes	No
Other	Change in arterial pH		Baseline and 60 minutes	No
Other	Change in heart rate		Baseline and 60 minutes	No
Other	change in blood pressure		Baseline and 60 minutes	No
Other	change in end-tidal oxygen and carbon dioxide partial pressure		Baseline and 60 minutes	Yes
Other	Change in arterial oxygen saturation		Baseline and 60 minutes	Yes
Other	Change in cardiac output	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)	Baseline and 60 minutes of poikilocapnic hypoxia	No
Other	Change in pulmonary venous blood velocity	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)	Baseline and 60 minutes of poikilocapnic hypoxia	No
Other	Hemoglobin		Baseline	No
Other	albumin		Baseline	No
Other	iron		Baseline	No
Primary	Change in ventilation	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)	Baseline and 60 minutes of poikilocapnic hypoxia	No
Primary	Change in pulmonary artery pressure	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)	Baseline and 60 minutes of poikilocapnic hypoxia	No
Secondary	Change in cerebral blood velocity	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)	Baseline and 60 minutes	No