<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/NCT02972411</url>
  </required_header>
  <id_info>
    <org_study_id>HospitalTS</org_study_id>
    <nct_id>NCT02972411</nct_id>
  </id_info>
  <brief_title>Controlled Hyperventilation as Prophylaxis for Acute Mountain Sickness</brief_title>
  <official_title>Controlled Hyperventilation as Prophylaxis for Acute Mountain Sickness: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital del Trabajador de Santiago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital del Trabajador de Santiago</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the safety and efficacy of the voluntary ventilatory response as&#xD;
      prophylaxis for acute mountain sickness, measured by the Lake Louise Self-Report Score,&#xD;
      comparing to a group using acetazolamide.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Acute mountain sickness (AMS) is a common condition among people who go to&#xD;
      altitude and stay at altitude. Acclimatization is the most important mechanism in order to&#xD;
      reduce the risk of AMS, however, this is not possible or adequate in a large part of the&#xD;
      cases. Recently, there are indications that adjustment of respiration by means of a voluntary&#xD;
      increase in the respiratory minute volume can have a similar prophylactic effect. The purpose&#xD;
      of this study is to measure the effect of the voluntary increase of the minute volume by&#xD;
      means of controlled hyperventilation as prophylaxis for acute mountain sickness without prior&#xD;
      acclimatization, with AMS being expressed in the Lake Louise Self-Report Score (LLSRS).&#xD;
&#xD;
      Objective: To investigate the safety and efficacy of the voluntary increase in minute&#xD;
      ventilation by means of controlled hyperventilation as prophylaxis for AMS, measured by the&#xD;
      LLSRS in a randomized controlled trial ascending to 4954m altitude.&#xD;
&#xD;
      Study design: Prospective randomized controlled trial, safety and efficacy.&#xD;
&#xD;
      Study population: 30 healthy subjects&#xD;
&#xD;
      Intervention: The investigational prophylaxis is controlled hyperventilation. Participants in&#xD;
      the interventional group will be trained to hyperventilate in a controlled fashion doing a&#xD;
      series of exercises during the 4 days prior to the ascent. They will also be taught in a&#xD;
      practical way to recognize early clinical signs and symptoms of hypocapnia.&#xD;
&#xD;
      Main study parameters/endpoints: Safety and efficacy measured by comparing the LLSRS between&#xD;
      the two groups. Target end-tidal CO2 ( PETCO2) will be measured to objectify adequate&#xD;
      hyperventilation. Symptoms of hypocapnia due to the (pre-)intervention as well as any adverse&#xD;
      events will be reported and analysed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2016</start_date>
  <completion_date type="Anticipated">May 2017</completion_date>
  <primary_completion_date type="Anticipated">May 2017</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Lake Louise Score</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>Intensity and prevalence of Acute Mountain Sickness. During Ascent.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PETCO2</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>Pressure of expired CO2, measured with a monitor in the moutain. During ascent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse oxygen saturation</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>During ascent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory rate</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>During ascent</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>During ascent</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Borg Scale</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>During ascent</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Training satisfactory. PETCO2 below 20 mmHg</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>After ascent.</description>
  </other_outcome>
  <other_outcome>
    <measure>Training satisfactory after Ascent. PETCO2 below 20mmHg</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>After ascent.</description>
  </other_outcome>
  <other_outcome>
    <measure>hypoxic ventilatory response</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Before ascent</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Altitude Sickness</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Voluntary increase in respiration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acetazolamide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Administration of Acetazolamide 125mg. since 24 hours before ascent and until 48 hours post altitude exposure, and absence of altitude sickness symptoms</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Voluntary ventilatory response</intervention_name>
    <description>Training of the subjects for voluntary increase in the respiratory minute ventilation</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetazolamide</intervention_name>
    <description>Acetazolamide 125mg. PO every 12 hours since 24 hours before ascent, until 48 hours at high altitude</description>
    <arm_group_label>Acetazolamide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Living at lower altitude than 900 meters&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiac or pulmonary comorbidity&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Infectious disease during the last 30 days&#xD;
&#xD;
          -  BMI&gt; 30&#xD;
&#xD;
          -  Pharmaceutical use as diuretics, corticosteroids, acetazolamide, or anti -inflammatory&#xD;
             drugs during the 2 weeks prior to the study&#xD;
&#xD;
          -  A history of high altitude cerebral edema or high altitude pulmonary edema&#xD;
&#xD;
          -  Cardiovascular risk factors such as a personal history of cardiovascular disease,&#xD;
             familial history of major adverse cardiovascular events (MACE) at age younger than 45&#xD;
             yrs, hypercholesterolemia and stroke.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sebastián Drago, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital del Trabajador Santiago</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sebastián Drago, MD</last_name>
    <phone>+56992191310</phone>
    <email>sebadrago@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Juan Campodónico, MD</last_name>
    <phone>+56981379351</phone>
    <email>campodonicouc@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>110 Sports and health center</name>
      <address>
        <city>Santiago</city>
        <zip>8320000</zip>
        <country>Chile</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mario Sandoval, MD</last_name>
      <phone>+56993593944</phone>
      <email>mariosandoval@110.cl</email>
    </contact>
  </location>
  <location_countries>
    <country>Chile</country>
  </location_countries>
  <reference>
    <citation>Bartsch P, Swenson ER. Clinical practice: Acute high-altitude illnesses. N Engl J Med. 2013 Jun 13;368(24):2294-302. doi: 10.1056/NEJMcp1214870.</citation>
    <PMID>23758234</PMID>
  </reference>
  <reference>
    <citation>Buijze GA, Hopman MT. Controlled hyperventilation after training may accelerate altitude acclimatization. Wilderness Environ Med. 2014 Dec;25(4):484-6. doi: 10.1016/j.wem.2014.04.009. Epub 2014 Oct 14. No abstract available.</citation>
    <PMID>25443751</PMID>
  </reference>
  <reference>
    <citation>Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, Zafren K, Hackett PH; Wilderness Medical Society. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. Wilderness Environ Med. 2010 Jun;21(2):146-55. doi: 10.1016/j.wem.2010.03.002. Epub 2010 Mar 10. Erratum In: Wilderness Environ Med. 2010 Dec;21(4):386.</citation>
    <PMID>20591379</PMID>
  </reference>
  <reference>
    <citation>Richalet JP, Larmignat P, Poitrine E, Letournel M, Canoui-Poitrine F. Physiological risk factors for severe high-altitude illness: a prospective cohort study. Am J Respir Crit Care Med. 2012 Jan 15;185(2):192-8. doi: 10.1164/rccm.201108-1396OC. Epub 2011 Oct 27.</citation>
    <PMID>22071330</PMID>
  </reference>
  <reference>
    <citation>Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med. 2010 Jun 1;152(11):726-32. doi: 10.7326/0003-4819-152-11-201006010-00232. Epub 2010 Mar 24.</citation>
    <PMID>20335313</PMID>
  </reference>
  <reference>
    <citation>Vargas M, Osorio J, Jimenez D, Moraga F, Sepulveda M, Del Solar J, Hudson C, Cortes G, Leon A. [Acute mountain sickness at 3500 and 4250 m. A study of symptom, incidence and severity]. Rev Med Chil. 2001 Feb;129(2):166-72. Spanish.</citation>
    <PMID>11351468</PMID>
  </reference>
  <reference>
    <citation>Acetazolamide in control of acute mountain sickness. Lancet. 1981 Jan 24;1(8213):180-3.</citation>
    <PMID>6109857</PMID>
  </reference>
  <reference>
    <citation>Bernardi L, Passino C, Spadacini G, Bonfichi M, Arcaini L, Malcovati L, Bandinelli G, Schneider A, Keyl C, Feil P, Greene RE, Bernasconi C. Reduced hypoxic ventilatory response with preserved blood oxygenation in yoga trainees and Himalayan Buddhist monks at altitude: evidence of a different adaptive strategy? Eur J Appl Physiol. 2007 Mar;99(5):511-8. doi: 10.1007/s00421-006-0373-8. Epub 2007 Jan 6.</citation>
    <PMID>17206440</PMID>
  </reference>
  <reference>
    <citation>Bernardi L, Schneider A, Pomidori L, Paolucci E, Cogo A. Hypoxic ventilatory response in successful extreme altitude climbers. Eur Respir J. 2006 Jan;27(1):165-71. doi: 10.1183/09031936.06.00015805.</citation>
    <PMID>16387950</PMID>
  </reference>
  <reference>
    <citation>Moore LG, Harrison GL, McCullough RE, McCullough RG, Micco AJ, Tucker A, Weil JV, Reeves JT. Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness. J Appl Physiol (1985). 1986 Apr;60(4):1407-12. doi: 10.1152/jappl.1986.60.4.1407.</citation>
    <PMID>3084449</PMID>
  </reference>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>October 25, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>November 21, 2016</last_update_submitted>
  <last_update_submitted_qc>November 21, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 23, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital del Trabajador de Santiago</investigator_affiliation>
    <investigator_full_name>Sebastián Drago Pérez</investigator_full_name>
    <investigator_title>Orthopaedic Surgeon</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperventilation</mesh_term>
    <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/NCT02972411
org study id: HospitalTS
nct id: NCT02972411
lead sponsor: 
has dmc: No
This study evaluates the safety and efficacy of the voluntary ventilatory response as
      prophylaxis for acute mountain sickness, measured by the Lake Louise Self-Report Score,
      comparing to a group using acetazolamide.
Rationale: Acute mountain sickness (AMS) is a common condition among people who go to
      altitude and stay at altitude. Acclimatization is the most important mechanism in order to
      reduce the risk of AMS, however, this is not possible or adequate in a large part of the
      cases. Recently, there are indications that adjustment of respiration by means of a voluntary
      increase in the respiratory minute volume can have a similar prophylactic effect. The purpose
      of this study is to measure the effect of the voluntary increase of the minute volume by
      means of controlled hyperventilation as prophylaxis for acute mountain sickness without prior
      acclimatization, with AMS being expressed in the Lake Louise Self-Report Score (LLSRS).

      Objective: To investigate the safety and efficacy of the voluntary increase in minute
      ventilation by means of controlled hyperventilation as prophylaxis for AMS, measured by the
      LLSRS in a randomized controlled trial ascending to 4954m altitude.

      Study design: Prospective randomized controlled trial, safety and efficacy.

      Study population: 30 healthy subjects

      Intervention: The investigational prophylaxis is controlled hyperventilation. Participants in
      the interventional group will be trained to hyperventilate in a controlled fashion doing a
      series of exercises during the 4 days prior to the ascent. They will also be taught in a
      practical way to recognize early clinical signs and symptoms of hypocapnia.

      Main study parameters/endpoints: Safety and efficacy measured by comparing the LLSRS between
      the two groups. Target end-tidal CO2 ( PETCO2) will be measured to objectify adequate
      hyperventilation. Symptoms of hypocapnia due to the (pre-)intervention as well as any adverse
      events will be reported and analysed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: Lake Louise Score
time frame: Up to 5 months
description: Intensity and prevalence of Acute Mountain Sickness. During Ascent.
measure: PETCO2
time frame: Up to 5 months
description: Pressure of expired CO2, measured with a monitor in the moutain. During ascent.
measure: Pulse oxygen saturation
time frame: Up to 5 months
description: During ascent.
measure: Respiratory rate
time frame: Up to 5 months
description: During ascent
measure: Heart rate
time frame: Up to 5 months
description: During ascent
measure: Borg Scale
time frame: Up to 5 months
description: During ascent
measure: Training satisfactory. PETCO2 below 20 mmHg
time frame: Up to 6 months
description: After ascent.
measure: Training satisfactory after Ascent. PETCO2 below 20mmHg
time frame: Up to 6 months
description: After ascent.
measure: hypoxic ventilatory response
time frame: Up to 6 months
description: Before ascent
arm group label: Intervention
arm group type: Experimental
description: Voluntary increase in respiration
arm group label: Acetazolamide
arm group type: Active Comparator
description: Administration of Acetazolamide 125mg. since 24 hours before ascent and until 48 hours post altitude exposure, and absence of altitude sickness symptoms
intervention type: Behavioral
intervention name: Voluntary ventilatory response
description: Training of the subjects for voluntary increase in the respiratory minute ventilation
arm group label: Intervention
intervention type: Drug
intervention name: Acetazolamide
description: Acetazolamide 125mg. PO every 12 hours since 24 hours before ascent, until 48 hours at high altitude
arm group label: Acetazolamide
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sebastián Drago, MD
role: Principal Investigator
affiliation: Hospital del Trabajador Santiago
last name: Sebastián Drago, MD
phone: +56992191310
email: sebadrago@gmail.com
last name: Juan Campodónico, MD
phone: +56981379351
email: campodonicouc@gmail.com
facility: 
status: Recruiting
contact: 
country: Chile
citation: Bartsch P, Swenson ER. Clinical practice: Acute high-altitude illnesses. N Engl J Med. 2013 Jun 13;368(24):2294-302. doi: 10.1056/NEJMcp1214870.
PMID: 23758234
citation: Buijze GA, Hopman MT. Controlled hyperventilation after training may accelerate altitude acclimatization. Wilderness Environ Med. 2014 Dec;25(4):484-6. doi: 10.1016/j.wem.2014.04.009. Epub 2014 Oct 14. No abstract available.
PMID: 25443751
citation: Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, Zafren K, Hackett PH; Wilderness Medical Society. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. Wilderness Environ Med. 2010 Jun;21(2):146-55. doi: 10.1016/j.wem.2010.03.002. Epub 2010 Mar 10. Erratum In: Wilderness Environ Med. 2010 Dec;21(4):386.
PMID: 20591379
citation: Richalet JP, Larmignat P, Poitrine E, Letournel M, Canoui-Poitrine F. Physiological risk factors for severe high-altitude illness: a prospective cohort study. Am J Respir Crit Care Med. 2012 Jan 15;185(2):192-8. doi: 10.1164/rccm.201108-1396OC. Epub 2011 Oct 27.
PMID: 22071330
citation: Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med. 2010 Jun 1;152(11):726-32. doi: 10.7326/0003-4819-152-11-201006010-00232. Epub 2010 Mar 24.
PMID: 20335313
citation: Vargas M, Osorio J, Jimenez D, Moraga F, Sepulveda M, Del Solar J, Hudson C, Cortes G, Leon A. [Acute mountain sickness at 3500 and 4250 m. A study of symptom, incidence and severity]. Rev Med Chil. 2001 Feb;129(2):166-72. Spanish.
PMID: 11351468
citation: Acetazolamide in control of acute mountain sickness. Lancet. 1981 Jan 24;1(8213):180-3.
PMID: 6109857
citation: Bernardi L, Passino C, Spadacini G, Bonfichi M, Arcaini L, Malcovati L, Bandinelli G, Schneider A, Keyl C, Feil P, Greene RE, Bernasconi C. Reduced hypoxic ventilatory response with preserved blood oxygenation in yoga trainees and Himalayan Buddhist monks at altitude: evidence of a different adaptive strategy? Eur J Appl Physiol. 2007 Mar;99(5):511-8. doi: 10.1007/s00421-006-0373-8. Epub 2007 Jan 6.
PMID: 17206440
citation: Bernardi L, Schneider A, Pomidori L, Paolucci E, Cogo A. Hypoxic ventilatory response in successful extreme altitude climbers. Eur Respir J. 2006 Jan;27(1):165-71. doi: 10.1183/09031936.06.00015805.
PMID: 16387950
citation: Moore LG, Harrison GL, McCullough RE, McCullough RG, Micco AJ, Tucker A, Weil JV, Reeves JT. Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness. J Appl Physiol (1985). 1986 Apr;60(4):1407-12. doi: 10.1152/jappl.1986.60.4.1407.
PMID: 3084449
responsible party type: Principal Investigator
investigator affiliation: Hospital del Trabajador de Santiago
investigator full name: Sebastián Drago Pérez
investigator title: Orthopaedic Surgeon
mesh term: Hyperventilation
mesh term: Altitude Sickness
mesh term: Acetazolamide
sharing ipd: No