Hypoxia, Altitude
Conditions
Brief summary
This study seeks to determine whether a simple, single intervention of Cetirizine / Zyrtec® use can improve exercise performance of active individuals when acutely exposed to altitude. For this project, healthy subjects will perform steady state and progressive work rate exercise, endurance performance time trials, and repeated sprint performance time trials in the laboratory at a simulated altitude of 3000m (9900ft) after dosing with 10 mg of Cetirizine or a placebo in a repeated measures design.
Detailed description
This study seeks to determine whether a simple, single intervention of Cetirizine / Zyrtec® use can improve exercise performance of active individuals when acutely exposed to altitude. For this project, healthy subjects will perform steady state and progressive work rate exercise, endurance performance time trials, and repeated sprint performance time trials in the laboratory at a simulated altitude of 3000m (9900ft) after dosing with 10 mg of Cetirizine or a placebo in a repeated measures design. Non-invasive techniques (pulse oximetry, near-infrared spectroscopy \[NIRS\]) will be utilized to measure changes in arterial oxyhemoglobin saturation and skeletal muscle oxygenation at the level of the microvasculature during exercise. It is expected that after Cetirizine, blood and muscle microvascular oxygenation during heavy exercise will improve compared to placebo, ultimately improving exercise performance at altitude. Subjects will be asked to report to the laboratory on a three occasions, separated by a minimum of 48 hours and a maximum of 14 days. For each subject, all testing sessions will be performed at the same time of day. Prior to each testing session, subjects will be asked to abstain from caffeine consumption for 12 hours. Subjects will also be asked to avoid alcohol consumption for 24 hours before testing, be at least 3-hour post prandial and avoid high-intensity exercise during the 24 hours leading to the exercise testing. Finally, subjects will be asked to consume a similar diet the night before, and the morning of, Sessions 2 and 3.
Interventions
DRUGCetirizine
Cetirizine tablet 10 mg
DRUGPlacebo oral capsule
Gelatin placebo
OTHERHypoxia
Exposure to a 14.3% oxygen environment simulating an altitude of 3,000m/9,000ft
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Physically active a minimum of 120 minutes a week, as determined by questionnaire * 18-35 years of age * Classified as low risk, based on the modified PAR-Q questionnaire, BMI, and non-smoking status * No history of pulmonary disease and pulmonary function classified as normal, as defined by the following measurements being 80% of predicted values: forced vital capacity (FVC), forced expired volume in one second (FEV1) and FEV1/FVC, according to the American Thoracic Society standards.
Exclusion criteria
* Current smoker * Women who are pregnant or could possibly be pregnant * BMI \> 25 kg/m2 * A 'yes' answer to any of the 14 questions on the PAR-Q pre-participation questionnaire * History of pulmonary disease or \<80% of predicted FCV, FEV1 and/or FEV1/FVC. * A history of renal or liver disease, due to possible interaction effect with Cetirizine * Currently taking any prescription or over the counter medications for the treatment of allergies, or taking any of the below listed drugs known to have a moderate or higher interaction effect with Cetirizine: isocarboxazid tranylcypromine bosutinib clobazam crizotinib daclatasvir eliglustat hyaluronidase lomitapide lurasidone ombitasvir/paritaprevir/ritonavir phenelzine ponatinib ritonavir vemurafenib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Performance Time | Performed 60min after pill ingestion | Time to complete 8km cycling time trial |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Histamine Concentrations at Baseline and Post-Exercise | baseline and immediately post-exercise, same day as pill ingestion | Plasma histamine concentrations (ng/mL) were determined baseline and post-exercise for each experimental condition. Baseline measures were taken immediately prior to exercise and the post-exercise measures were taken 5-10 minutes after the cessation of exercise. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited by direct email to the administrators of the Indiana University ROTC program. It was made clear that participation of cadets was voluntary in nature and was not be a requirement of ROTC duties. Active recruitment took place from 08/2017 to 03/2018.
Pre-assignment details
Enrolled participants were excluded prior to arm/group assignment if they had abnormal pulmonary function, or voluntarily discontinued with study procedures after completing a graded maximal exercise test and familiarization trial of exercise performance tests on a cycle ergometer. Two subjects withdrew prior to initial group assignments.
Participants by arm
| Arm | Count |
|---|---|
| Subjects Completing All 3 Study Arms Completed: Hypoxia/ Cetirizine (14.3% oxygen with 10mg cetirizine), Hypoxia/ Placebo (21% oxygen with gelatin placebo), and Normoxia/Placebo (21% oxygen with gelatin placebo) | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Washout (>6d) | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 1 |
| Third Intervention (d1) | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Subjects Completing All 3 Study Arms | — |
|---|---|---|
| Age, Categorical <=18 years | 1 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 7 Participants | — |
| Age, Continuous | 20 years STANDARD_DEVIATION 1 | — |
| Body Fat Percentage | 12.1 percentage STANDARD_DEVIATION 3.9 | — |
| Body Mass Index | 23 kg/m^2 STANDARD_DEVIATION 2 | — |
| Height | 172 cm STANDARD_DEVIATION 8 | — |
| Maximal Aerobic Capacity (VO2max) | 44.3 ml/kg/min STANDARD_DEVIATION 8.3 | — |
| Physical Activity | 441 minutes per week STANDARD_DEVIATION 310 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 8 participants | — |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 6 Participants | — |
| Weight | 68.3 kg STANDARD_DEVIATION 11.1 | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 1 / 11 | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 11 |
Outcome results
Primary
Performance Time
Time to complete 8km cycling time trial
Time frame: Performed 60min after pill ingestion
Population: Subjects who completed all three interventions were included in the outcome analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cetirizine and Hypoxia | Performance Time | 17.03 minutes | Standard Deviation 1.92 |
| Placebo and Hypoxia | Performance Time | 18.08 minutes | Standard Deviation 2.87 |
| Placebo and Normoxia | Performance Time | 16.32 minutes | Standard Deviation 1.98 |
p-value: 0.04795% CI: [0.01, 2.11]ANOVA
Secondary
Plasma Histamine Concentrations at Baseline and Post-Exercise
Plasma histamine concentrations (ng/mL) were determined baseline and post-exercise for each experimental condition. Baseline measures were taken immediately prior to exercise and the post-exercise measures were taken 5-10 minutes after the cessation of exercise.
Time frame: baseline and immediately post-exercise, same day as pill ingestion
Population: Subjects included are those who completed all three intervention visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cetirizine and Hypoxia | Plasma Histamine Concentrations at Baseline and Post-Exercise | .36 ng/mL | Standard Deviation 0.14 |
| Placebo and Hypoxia | Plasma Histamine Concentrations at Baseline and Post-Exercise | .49 ng/mL | Standard Deviation 0.21 |
| Placebo and Normoxia | Plasma Histamine Concentrations at Baseline and Post-Exercise | .56 ng/mL | Standard Deviation 0.39 |
| Placebo and Hypoxia (Post-Exercise) | Plasma Histamine Concentrations at Baseline and Post-Exercise | .61 ng/mL | Standard Deviation 0.34 |
| Placebo and Normoxia (Baseline) | Plasma Histamine Concentrations at Baseline and Post-Exercise | .37 ng/mL | Standard Deviation 0.09 |
| Placebo and Normoxia (Post-Exercise) | Plasma Histamine Concentrations at Baseline and Post-Exercise | .47 ng/mL | Standard Deviation 0.15 |
p-value: 0.327ANOVA
p-value: 0.557ANOVA