AZ, MZ, and the Pulmonary System Response to Hypoxia

NCT02760121 | Completed Phase 4

• 1 other identifier: H16-00028
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Altitude Sickness; Hypertension, Pulmonary

Keywords

Acetazolamide; Methazolamide; Control of breathing; Hypoxic pulmonary vasoconstriction

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (1)

• Change in cerebral blood velocity

  Baseline and 60 minutes

Other Outcomes (12)

• change in arterial oxygen partial pressure

  Baseline and 60 minutes

• Change in arterial carbon dioxide partial pressure

  Baseline and 60 minutes

• Change in arterial pH

  Baseline and 60 minutes

Study Arms (3)

Acetazolamide

EXPERIMENTAL

Participants will be dosed 250mg Acetazolamide (p.o.) three times per day for two days prior to and a single dose on the day of study.

Drug: Acetazolamide

Methazolamide

EXPERIMENTAL

Participants will be dosed 100mg Methazolamide (p.o.) twice daily separated by a placebo for two days prior to and a single dose on the day of study. The placebo dose is provided to match the dosing schedule between conditions.

Drug: Methazolamide

Placebo

PLACEBO COMPARATOR

Participants will take (p.o.) placebo pills three times per day for two days prior to and a single dose on the day of study.

Drug: Placebo

Interventions

Acetazolamide DRUG

Acetazolamide

Methazolamide DRUG

Methazolamide

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• years of age
• regularly physically active
• male

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia

Kelowna, British Columbia, V1V 1V7, Canada

Location

MeSH Terms

Conditions

Altitude Sickness; Hypertension, Pulmonary

Interventions

Acetazolamide; Methazolamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Glen E Foster, Ph.D.

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2016
• First Posted: May 3, 2016
• Study Start: May 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: October 19, 2016

Record last verified: 2016-10

Locations

CA (1)