Sickness Evaluation at Altitude With Acetazolamide at Relative Doses (SEAWARDII)

October 18, 2019 updated by: Carrie Jurkiewicz, Stanford University
The specific aim of this study is to evaluate whether acetazolamide 125mg daily is no worse than acetazolamide 250mg daily in decreasing the incidence of acute mountain sickness (AMS) in travelers to high altitude. The study population is hikers who are ascending at their own rate under their own power in a true hiking environment at the White Mountain Research Station, Owen Valley Lab (OVL) and Bancroft Station (BAR), Bancroft Peak, White Mountain, California

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Acute mountain sickness (AMS) is a constellation of symptoms including headache, sleep disturbance, fatigue, dizziness, and nausea, vomiting, or anorexia that commonly occurs in travelers ascending to altitudes above 2,500m. AMS incidence varies based on altitude and ascent profile with rates reported from 25 to 75% in tourists, trekkers, and mountaineers at North American altitudes. Symptom onset is typically six to twelve hours after arrival at high altitude. This self-limited disease can be debilitating when severe, and left unrecognized or untreated may progress to potentially fatal high altitude cerebral edema (HACE). While gradual ascent has proven effective in preventing AMS, this approach is often impractical to recreationists, search and rescue, disaster relief, and military operations.

Acetazolamide increases minute ventilation by 10-20% in subjects at altitude, and hastens acclimatization. It is well established that acetazolamide's main site of action is in the kidney, where it generates a metabolic acidosis through renal bicarbonate wasting and attenuates the effects of hypoxemic-induced respiratory alkalosis. Recommended dosing of acetazolamide for AMS prophylaxis has significantly decreased since early days of use in the 1960s. The current recommended dose of acetazolamide for this indication is 125 mg twice daily, as opposed to historical recommendations of 500mg or 750mg daily. Multiple meta-analyses have concluded that when compared with higher doses, 250mg of acetazolamide daily has been shown to be equally efficacious, with the added benefit of decreasing side effects including paresthesias and dysgeusia. A randomized controlled trial confirmed effectiveness of acetazolamide 125mg twice daily in prevention of AMS when started prior to ascent. In this study, it was found that 125mg twice daily corresponded to a range of 3-5mg/kg/day, depending on subject weight. Within this range, those on the lower dosing range did not have a greater incidence or severity of AMS. For subjects weighing between 50kg (110 lbs) - 83kg (183 lbs), a dose of 250mg/day acetazolamide would fall in this range. Interestingly, mountaineers and trekkers have anecdotally reported protection against AMS with 125mg/day of acetazolamide, a dose below 3-5mg/kg for anyone over 41kg (91lb).

Finding the lowest effective dose of acetazolamide for AMS prophylaxis is important because side effects of this medication can mimic AMS, decreasing the specificity of disease scoring on the validated Lake Louise Questionnaire (LLQ) and subsequent AMS diagnosis and chemoprophylactic effectiveness.Keeping in mind that LLQ is scored based on symptoms of headache, gastrointestinal symptoms, fatigue and weakness, and dizziness and lightheadedness, whatever effect acetazolamide has on AMS prevention may be obscured by its side effects that mimic the very same disease. Falsely positive LLQ scores in trekkers and mountaineers taking acetazolamide prophylaxis may lead to unnecessary pharmacologic treatment or even evacuation. From the perspective of high altitude research, participants randomized to or already taking acetazolamide may skew study results by decreasing LLQ specificity and potentially leading researchers to overestimate incidence of AMS.

Study Type

Interventional

Enrollment (Actual)

108

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Bishop, California, United States, 93514
        • White Mountain Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Able to complete moderate hike at altitude
  • Live at elevation < 4,000 ft
  • Able to arrange own transportation to study site
  • Available for full study duration (Friday night - Sunday morning)

Exclusion Criteria:

  • Pregnancy
  • Slept at altitude > 4,000 ft within 1 week of study
  • Allergy to acetazolamide or sulfa drugs
  • NSAIDs, acetazolamide, or corticosteroids within 48 hours prior to study start
  • History of severe anemia, severe heart disease, advanced COPD/emphysema or sickle cell disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acetazolamide 125mg twice daily
Acetazolamide pill 125mg twice daily by mouth, started the night prior to ascent and continued for 3 total doses
Drug: Acetazolamide Pill
Acetazolamide pill
Other Names:
  • Diamox
Experimental: Acetazolamide 62.5mg twice daily
Acetazolamide pill 62.5mg twice daily by mouth, started the night prior to ascent and continued for 3 total doses
Drug: Acetazolamide Pill
Acetazolamide pill
Other Names:
  • Diamox

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of acute mountain sickness
Time Frame: 2 days
Incidence of acute mountain sickness by Lake Louise Questionnaire
2 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

  • Principal Investigator: Carrie Jurkiewicz, MD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 9, 2019

Primary Completion (Actual)

September 29, 2019

Study Completion (Actual)

September 29, 2019

Study Registration Dates

First Submitted

January 31, 2019

First Submitted That Met QC Criteria

January 31, 2019

First Posted (Actual)

February 4, 2019

Study Record Updates

Last Update Posted (Actual)

October 22, 2019

Last Update Submitted That Met QC Criteria

October 18, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 49724

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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