Controlled Hyperventilation as Prophylaxis for Acute Mountain Sickness

Controlled Hyperventilation as Prophylaxis for Acute Mountain Sickness: A Randomized Controlled Trial

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.

Study Overview

• Status: Unknown
• Conditions: Altitude Sickness
• Intervention / Treatment: Behavioral: Voluntary ventilatory response; Drug: Acetazolamide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sebastián Drago, MD; Phone Number: +56992191310; Email: sebadrago@gmail.com
• Study Contact Backup: Name: Juan Campodónico, MD; Phone Number: +56981379351; Email: campodonicouc@gmail.com

Study Locations

• Chile
  • Santiago, Chile, 8320000
    • Recruiting
    • 110 Sports and health center
    • Contact: Mario Sandoval, MD; Phone Number: +56993593944; Email: mariosandoval@110.cl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Living at lower altitude than 900 meters

Exclusion Criteria:

• Cardiac or pulmonary comorbidity
• Smoking
• Infectious disease during the last 30 days
• BMI> 30
• Pharmaceutical use as diuretics, corticosteroids, acetazolamide, or anti -inflammatory drugs during the 2 weeks prior to the study
• A history of high altitude cerebral edema or high altitude pulmonary edema
• Cardiovascular risk factors such as a personal history of cardiovascular disease, familial history of major adverse cardiovascular events (MACE) at age younger than 45 yrs, hypercholesterolemia and stroke.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention; Voluntary increase in respiration	Behavioral: Voluntary ventilatory response; Training of the subjects for voluntary increase in the respiratory minute ventilation
ACTIVE_COMPARATOR: Acetazolamide; Administration of Acetazolamide 125mg. since 24 hours before ascent and until 48 hours post altitude exposure, and absence of altitude sickness symptoms	Drug: Acetazolamide; Acetazolamide 125mg. PO every 12 hours since 24 hours before ascent, until 48 hours at high altitude

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lake Louise Score	Intensity and prevalence of Acute Mountain Sickness. During Ascent.	Up to 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PETCO2	Pressure of expired CO2, measured with a monitor in the moutain. During ascent.	Up to 5 months
Pulse oxygen saturation	During ascent.	Up to 5 months
Respiratory rate	During ascent	Up to 5 months
Heart rate	During ascent	Up to 5 months
Borg Scale	During ascent	Up to 5 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Training satisfactory. PETCO2 below 20 mmHg	After ascent.	Up to 6 months
Training satisfactory after Ascent. PETCO2 below 20mmHg	After ascent.	Up to 6 months
hypoxic ventilatory response	Before ascent	Up to 6 months

Collaborators and Investigators

• Sponsor: Hospital del Trabajador de Santiago
• Investigators: Principal Investigator: Sebastián Drago, MD, Hospital del Trabajador Santiago

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Acetazolamide in control of acute mountain sickness. Lancet. 1981 Jan 24;1(8213):180-3.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (ANTICIPATED): May 1, 2017
• Study Completion (ANTICIPATED): May 1, 2017

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (ESTIMATE): November 23, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): November 23, 2016
• Last Update Submitted That Met QC Criteria: November 21, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Altitude Sickness; Hyperventilation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: HospitalTS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO