Altitude SicknessPhase 4NCT02760121
AZ, MZ, and the Pulmonary System Response to Hypoxia
A Phase 4 study testing Acetazolamide and Methazolamide in people with Altitude Sickness and Hypertension, Pulmonary, run by University of British Columbia at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Altitude Sickness, Hypertension, Pulmonary
- What is being tested?
- Acetazolamide and Methazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteCanada
- Study dates
- May 2016to Aug 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-40 years of age
- regularly physically active
- male
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Carbonic Anhydrase Inhibitors on 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.
- Conditions
- Altitude Sickness, Hypertension, Pulmonary
- Being tested
- Acetazolamide, Methazolamide, Placebo
- Keywords
- Acetazolamide, Methazolamide, Control of breathing, Hypoxic pulmonary vasoconstriction
- Medical subject headings
- Altitude Sickness, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetazolamideDrug
MethazolamideDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: Baseline and 60 minutes of poikilocapnic hypoxia
Secondary outcomes (1)
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)
Measured: Baseline and 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2016 (estimated)
- Study startMay 2016
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Altitude SicknessStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Glen E Foster, Ph.D., Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02760121
- Sponsor's protocol ID
- H16-00028
- Status last verified
- Oct 2016
- First submitted
- 20 Apr 2016
- Last updated
- 19 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Carbonic Anhydrase Inhibitors on the Pulmonary System Response to Hypoxia
- ClinicalTrials.gov ID
- NCT02760121
- Acronym / sponsor ID
- H16-00028
- Conditions
- Altitude Sickness, Hypertension, Pulmonary
- Keywords
- Acetazolamide, Methazolamide, Control of breathing, Hypoxic pulmonary vasoconstriction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- May 2016
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 3 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide | Experimental | Drug: AcetazolamideParticipants 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. |
| Methazolamide | Experimental | Drug: MethazolamideParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will take (p.o.) placebo pills three times per day for two days prior to and a single dose on the day of study. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 18-40 years of age
- regularly physically active
- male
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acetazolamide | Drug | Acetazolamide |
| Methazolamide | Drug | Methazolamide |
| Placebo | Drug | Placebo |
Primary outcome
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)
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)
1 secondary outcome
Change in cerebral blood velocity
Time frame: Baseline and 60 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Glen E Foster, Ph.D. principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Acetazolamide and Methazolamide in people with Altitude Sickness and Hypertension, Pulmonary, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ventilation (time frame: Baseline and 60 minutes of poikilocapnic hypoxia). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2016.