<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03828474</url>
  </required_header>
  <id_info>
    <org_study_id>49724</org_study_id>
    <nct_id>NCT03828474</nct_id>
  </id_info>
  <brief_title>Sickness Evaluation at Altitude With Acetazolamide at Relative Doses</brief_title>
  <acronym>SEAWARDII</acronym>
  <official_title>Sickness Evaluation at Altitude With Acetazolamide at Relative Doses</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The specific aim of this study is to evaluate whether acetazolamide 125mg daily is no worse&#xD;
      than acetazolamide 250mg daily in decreasing the incidence of acute mountain sickness (AMS)&#xD;
      in travelers to high altitude. The study population is hikers who are ascending at their own&#xD;
      rate under their own power in a true hiking environment at the White Mountain Research&#xD;
      Station, Owen Valley Lab (OVL) and Bancroft Station (BAR), Bancroft Peak, White Mountain,&#xD;
      California&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute mountain sickness (AMS) is a constellation of symptoms including headache, sleep&#xD;
      disturbance, fatigue, dizziness, and nausea, vomiting, or anorexia that commonly occurs in&#xD;
      travelers ascending to altitudes above 2,500m. AMS incidence varies based on altitude and&#xD;
      ascent profile with rates reported from 25 to 75% in tourists, trekkers, and mountaineers at&#xD;
      North American altitudes. Symptom onset is typically six to twelve hours after arrival at&#xD;
      high altitude. This self-limited disease can be debilitating when severe, and left&#xD;
      unrecognized or untreated may progress to potentially fatal high altitude cerebral edema&#xD;
      (HACE). While gradual ascent has proven effective in preventing AMS, this approach is often&#xD;
      impractical to recreationists, search and rescue, disaster relief, and military operations.&#xD;
&#xD;
      Acetazolamide increases minute ventilation by 10-20% in subjects at altitude, and hastens&#xD;
      acclimatization. It is well established that acetazolamide's main site of action is in the&#xD;
      kidney, where it generates a metabolic acidosis through renal bicarbonate wasting and&#xD;
      attenuates the effects of hypoxemic-induced respiratory alkalosis. Recommended dosing of&#xD;
      acetazolamide for AMS prophylaxis has significantly decreased since early days of use in the&#xD;
      1960s. The current recommended dose of acetazolamide for this indication is 125 mg twice&#xD;
      daily, as opposed to historical recommendations of 500mg or 750mg daily. Multiple&#xD;
      meta-analyses have concluded that when compared with higher doses, 250mg of acetazolamide&#xD;
      daily has been shown to be equally efficacious, with the added benefit of decreasing side&#xD;
      effects including paresthesias and dysgeusia. A randomized controlled trial confirmed&#xD;
      effectiveness of acetazolamide 125mg twice daily in prevention of AMS when started prior to&#xD;
      ascent. In this study, it was found that 125mg twice daily corresponded to a range of&#xD;
      3-5mg/kg/day, depending on subject weight. Within this range, those on the lower dosing range&#xD;
      did not have a greater incidence or severity of AMS. For subjects weighing between 50kg (110&#xD;
      lbs) - 83kg (183 lbs), a dose of 250mg/day acetazolamide would fall in this range.&#xD;
      Interestingly, mountaineers and trekkers have anecdotally reported protection against AMS&#xD;
      with 125mg/day of acetazolamide, a dose below 3-5mg/kg for anyone over 41kg (91lb).&#xD;
&#xD;
      Finding the lowest effective dose of acetazolamide for AMS prophylaxis is important because&#xD;
      side effects of this medication can mimic AMS, decreasing the specificity of disease scoring&#xD;
      on the validated Lake Louise Questionnaire (LLQ) and subsequent AMS diagnosis and&#xD;
      chemoprophylactic effectiveness.Keeping in mind that LLQ is scored based on symptoms of&#xD;
      headache, gastrointestinal symptoms, fatigue and weakness, and dizziness and lightheadedness,&#xD;
      whatever effect acetazolamide has on AMS prevention may be obscured by its side effects that&#xD;
      mimic the very same disease. Falsely positive LLQ scores in trekkers and mountaineers taking&#xD;
      acetazolamide prophylaxis may lead to unnecessary pharmacologic treatment or even evacuation.&#xD;
      From the perspective of high altitude research, participants randomized to or already taking&#xD;
      acetazolamide may skew study results by decreasing LLQ specificity and potentially leading&#xD;
      researchers to overestimate incidence of AMS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 9, 2019</start_date>
  <completion_date type="Actual">September 29, 2019</completion_date>
  <primary_completion_date type="Actual">September 29, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Double blind randomized controlled trial</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Visually identical pills</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of acute mountain sickness</measure>
    <time_frame>2 days</time_frame>
    <description>Incidence of acute mountain sickness by Lake Louise Questionnaire</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">108</enrollment>
  <condition>Acute Mountain Sickness</condition>
  <arm_group>
    <arm_group_label>Acetazolamide 125mg twice daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acetazolamide pill 125mg twice daily by mouth, started the night prior to ascent and continued for 3 total doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acetazolamide 62.5mg twice daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acetazolamide pill 62.5mg twice daily by mouth, started the night prior to ascent and continued for 3 total doses</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetazolamide Pill</intervention_name>
    <description>Acetazolamide pill</description>
    <arm_group_label>Acetazolamide 125mg twice daily</arm_group_label>
    <arm_group_label>Acetazolamide 62.5mg twice daily</arm_group_label>
    <other_name>Diamox</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to complete moderate hike at altitude&#xD;
&#xD;
          -  Live at elevation &lt; 4,000 ft&#xD;
&#xD;
          -  Able to arrange own transportation to study site&#xD;
&#xD;
          -  Available for full study duration (Friday night - Sunday morning)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Slept at altitude &gt; 4,000 ft within 1 week of study&#xD;
&#xD;
          -  Allergy to acetazolamide or sulfa drugs&#xD;
&#xD;
          -  NSAIDs, acetazolamide, or corticosteroids within 48 hours prior to study start&#xD;
&#xD;
          -  History of severe anemia, severe heart disease, advanced COPD/emphysema or sickle cell&#xD;
             disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carrie Jurkiewicz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>White Mountain Research Center</name>
      <address>
        <city>Bishop</city>
        <state>California</state>
        <zip>93514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>van Patot MC, Leadbetter G 3rd, Keyes LE, Maakestad KM, Olson S, Hackett PH. Prophylactic low-dose acetazolamide reduces the incidence and severity of acute mountain sickness. High Alt Med Biol. 2008 Winter;9(4):289-93. doi: 10.1089/ham.2008.1029.</citation>
    <PMID>19115912</PMID>
  </reference>
  <reference>
    <citation>Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. J Appl Physiol (1985). 2007 Apr;102(4):1313-22. doi: 10.1152/japplphysiol.01572.2005. Epub 2006 Oct 5.</citation>
    <PMID>17023566</PMID>
  </reference>
  <reference>
    <citation>Hackett PH, Roach RC. High-altitude illness. N Engl J Med. 2001 Jul 12;345(2):107-14. doi: 10.1056/NEJM200107123450206. No abstract available.</citation>
    <PMID>11450659</PMID>
  </reference>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>October 18, 2019</last_update_submitted>
  <last_update_submitted_qc>October 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Carrie Jurkiewicz</investigator_full_name>
    <investigator_title>Clinical Instructor, Department of Emergency Medicine</investigator_title>
  </responsible_party>
  <keyword>acetazolamide</keyword>
  <keyword>chemoprophylaxis</keyword>
  <keyword>altitude</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Altitude Sickness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetazolamide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03828474
org study id: 49724
nct id: NCT03828474
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
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
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double blind randomized controlled trial
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Visually identical pills
measure: Incidence of acute mountain sickness
time frame: 2 days
description: Incidence of acute mountain sickness by Lake Louise Questionnaire
arm group label: Acetazolamide 125mg twice daily
arm group type: Experimental
description: Acetazolamide pill 125mg twice daily by mouth, started the night prior to ascent and continued for 3 total doses
arm group label: Acetazolamide 62.5mg twice daily
arm group type: Experimental
description: Acetazolamide pill 62.5mg twice daily by mouth, started the night prior to ascent and continued for 3 total doses
intervention type: Drug
intervention name: Acetazolamide Pill
description: Acetazolamide pill
arm group label: Acetazolamide 125mg twice daily
arm group label: Acetazolamide 62.5mg twice daily
other name: Diamox
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Carrie Jurkiewicz, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
citation: van Patot MC, Leadbetter G 3rd, Keyes LE, Maakestad KM, Olson S, Hackett PH. Prophylactic low-dose acetazolamide reduces the incidence and severity of acute mountain sickness. High Alt Med Biol. 2008 Winter;9(4):289-93. doi: 10.1089/ham.2008.1029.
PMID: 19115912
citation: Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. J Appl Physiol (1985). 2007 Apr;102(4):1313-22. doi: 10.1152/japplphysiol.01572.2005. Epub 2006 Oct 5.
PMID: 17023566
citation: Hackett PH, Roach RC. High-altitude illness. N Engl J Med. 2001 Jul 12;345(2):107-14. doi: 10.1056/NEJM200107123450206. No abstract available.
PMID: 11450659
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Carrie Jurkiewicz
investigator title: Clinical Instructor, Department of Emergency Medicine
mesh term: Altitude Sickness
mesh term: Acetazolamide
sharing ipd: No