Clinical trial NCT02760121: AZ, MZ, and the Pulmonary System Response to Hypoxia
Official title: The Effect of Carbonic Anhydrase Inhibitors on the Pulmonary System Response to Hypoxia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Altitude Sickness
Hypertension, Pulmonary
Keywords: Acetazolamide
Methazolamide
Control of breathing
Hypoxic pulmonary vasoconstriction
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2016-05-03
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in ventilation
timeFrame: Baseline and 60 minutes of poikilocapnic hypoxia
measure: Change in pulmonary artery pressure
timeFrame: Baseline and 60 minutes of poikilocapnic hypoxia
Secondary outcomes:
measure: Change in cerebral blood velocity
timeFrame: Baseline and 60 minutes
Other outcomes:
measure: change in arterial oxygen partial pressure
timeFrame: Baseline and 60 minutes
measure: Change in arterial carbon dioxide partial pressure
timeFrame: Baseline and 60 minutes
measure: Change in arterial pH
timeFrame: Baseline and 60 minutes
measure: Change in heart rate
timeFrame: Baseline and 60 minutes
measure: change in blood pressure
timeFrame: Baseline and 60 minutes
measure: change in end-tidal oxygen and carbon dioxide partial pressure
timeFrame: Baseline and 60 minutes
measure: Change in arterial oxygen saturation
timeFrame: Baseline and 60 minutes
measure: Change in cardiac output
timeFrame: Baseline and 60 minutes of poikilocapnic hypoxia
measure: Change in pulmonary venous blood velocity
timeFrame: Baseline and 60 minutes of poikilocapnic hypoxia
measure: Hemoglobin
timeFrame: Baseline
measure: albumin
timeFrame: Baseline
measure: iron
timeFrame: Baseline
Locations:
city: Kelowna
country: Canada
facility: University of British Columbia
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Glen E Foster, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: