Effects of Non-steroidal Anti-inflammatory Drugs (NSAIDS) on Acclimatization to High Altitude

Ibuprofen is often taken by travelers to high altitude to treat the symptoms of acute mountain sickness such as headache and malaise. However, the blunting of inflammation by ibuprofen may slow the process of acclimatization to altitude, which relies on mediators of inflammation for adjustments in breathing.

The study randomizes healthy subjects to receive ibuprofen or placebo and then ascend to altitude (12,500 feet). Blood cytokines and non-invasive measurements of blood and tissue oxygen levels will be made for 48 hours at altitude. The hypothesis being tested is that subjects receiving ibuprofen will have lower blood and tissue oxygen levels after 48 hours at altitude than will placebo subjects.

Study Overview

• Status: Completed
• Conditions: High Altitude
• Intervention / Treatment: Drug: Ibuprofen; Drug: Sugar pill

Detailed Description

The study will begin with 2 days of studies in San Francisco (sea level baseline). Measurements will include non-invasive measurements of blood and tissue oxygen and venous blood draws for cytokine levels.

The altitude part of the study involves ascent to the University of California's White Mountain Research Center Barcroft Laboratory, at 12,500 feet elevation. The subjects will remain at that altitude for at least 48 hours for measurements of oxygenation and blood cytokines.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Bishop, California, United States, 95740
      • White Mountain Research Center
    • San Francisco, California, United States, 94143
      • UCSF Hypoxia Research Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy subjects The group of subjects in this experiment will be composed of healthy adult volunteers, over age 18 and under age 65, of any ethnic group, in good physical and mental health. We expect to enroll approximately 20 subjects. The ethnic groups represented will depend on the ethnicity of those who wish to be subjects, but no ethnic groups will be specifically sought after or rejected.

Exclusion Criteria:

Subjects will be specifically excluded according to the following criteria:

1. History of any clinically significant medical condition, particularly abnormal respiratory, cardiovascular, neurological, hematological, renal or hepatic function. A medical history and physical exam will be performed at the screening session for each subject. We will use this to determine whether the subjects are healthy and without any history of these conditions. No laboratory workup will be required
2. Regular smokers (more than 1 cigarette or cigar per day).
3. Currently active or recently treated systemic or serious local infection.
4. Recent regular use of prescription medications or regular physician care for any significant medical condition.
5. A history of high altitude pulmonary edema or high altitude cerebral edema.
6. Recent exposure to altitude (>8000 ft) in the last month or having slept at an altitude >6000 feet in the last month.
7. Inability to provide written informed consent or to be able to complete the experiment.
8. Pregnancy as determined by a urine pregnancy test if subjects believe they might be pregnant
9. Allergy to non-steroid anti-inflammatory drugs (NSAIDs) or subjects reporting history or symptoms of ulcers or other ibuprofen related contraindications discussed with the screening physician.
10. Heavy coffee drinkers or caffeine users will be advised that they may suffer rebound headache when restricted from caffeinated beverages on measurement days, and asked to carefully consider any continuing participation in the study after abstaining from caffeine during their first sea level measurements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ibuprofen plus ascent to high altitude; subjects randomized to this arm will take ibuprofen 200 mg 3 times daily during ascent and at altitude.	Drug: Ibuprofen; We are simply testing if taking ibuprofen upon ascent to altitude is associated with a delayed acclimatization response to the high altitude hypoxia.; Other Names: motrin
Placebo Comparator: sugar pill plus ascent to high altitude; subjects randomized to this arm will receive the placebo	Drug: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood cytokine levels	venous blood sample, once a day	on days 1 and 2 at sea level, on arrival at altitude and daily for 2 days
cerebral blood flow	optical/non-invasive measure of frontal cortex cerebral blood flow with an FDA-approved device	once daily for 2 days at sea level, on arrival at altitude and once daily at altitude for 2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pulse oximetry	finger pulse oximetry with an FDA approved pulse oximeter	once a day for 2 days at sea level, on arrival at altitude and daily for 2 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
cerebral oximetry	non-invasive measurements of cerebral oxygenation with an FDA approved device	once daily for 2 days at sea level, on arrival at altitude and daily for 2 days
acute mountain sickness inventory	standard questionnaire concerning symptoms associated with acute mountain sickness	once a day at both sea level (2 days) and altitude (2 days)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Philip Bickler, PhD/MD, University of California, San Francisco; Principal Investigator: John Feiner, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: September 3, 2014
• First Submitted That Met QC Criteria: September 3, 2014
• First Posted (Estimate): September 8, 2014

Study Record Updates

• Last Update Posted (Actual): April 6, 2021
• Last Update Submitted That Met QC Criteria: April 2, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: altitude; ibuprofen; hypoxia; mountain sickness
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Altitude Sickness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: Ibuprofen and Altitude; IRB#14-14110 (Other Identifier: UCSF IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Deidentified data may be shared with colleagues at other University of California campuses or affiliated academic institutions. No subject identifiers will be included.
• IPD Sharing Time Frame: To study completion.
• IPD Sharing Access Criteria: De-identified data set only.
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR)