The Effect of a Multi-strain Probiotic on Acclimatization to High Altitude

The Effect of a Multi-strain Probiotic SLAB51 (Sivomixx800®) on Acclimatization to High Altitude

The goal of this study is to learn if the probiotic SLAB51 (Sivomixx800®) works to enhance acclimatization to high altitude in humans. The main questions it aims to answer are:

Does SLAB51 improve oxygen saturation during high-altitude exposure? Researchers will compare SLAB51 to a placebo (a substance that contains no probiotic) to see if SLAB51 works to enhance high-altitude acclimatization.

Participants will:

Take SLAB51 or a placebo three times daily during two separate three-night acclimatization periods at high altitude, spaced at least six weeks apart.

Complete baseline measurements at sea level. Visit the high-altitude Barcroft Station (3,801 m) at the University of California White Mountain Research Center for physiological measurements and assessments.

Undergo assessments including oxygen saturation, ventilation, heart rate, blood pressure, sleep studies, cognitive assessments, exercise capacity, Acute Mountain Sickness scores, and provide blood, fecal, and urine samples for advanced analyses.

Study Overview

• Status: Active, not recruiting
• Conditions: Probiotics
• Intervention / Treatment: Dietary supplement: SLAB51

Detailed Description

Individuals will be recruited to participate in a double-blind, placebo controlled, cross-over study receiving placebo or the nutritional supplement probiotic SLAB51 (Sivomixx800®) during exposure to high altitude to test the effects of SLAB51 on high-altitude acclimatization.

Humans face significant physiological detriments when they ascend to high altitude due to hypobaric hypoxia, and physiological changes are crucial for acclimatization to this stressful environment. Currently, there are limited interventions to improve acclimatization to high altitude. The investigators conducting this study will test if the probiotic SLAB51 improves oxygen saturation and mitigates negative outcomes often experienced during acclimatization to high altitude through studies performed at sea level and at the high-altitude Barcroft Station (3,801 m) at the University of California White Mountain Research Center.

Preliminary studies indicate that ingestion of SLAB51 significantly improves oxygenation in humans during physical exercise in simulated altitude within a hypobaric chamber, in a pressurized airplane cabin during commercial flight, in premature born babies, and in COVID-19 patients. Here, the investigators explore whether ingestion of SLAB51 affects acclimatization to high altitude in healthy humans. Physiological measurements include oxygen saturation (O2 Sat or SpO2 during wakefulness and sleep, primary outcomes) as well as ventilation, heart rate, blood pressure, sleep studies, cognitive assessments, exercise capacity, measurement of the Acute Mountain Sickness score, and the collection of blood, fecal, and urine samples to further explored through transcriptomics, methylation, metabolomics, and proteomics. All measurements will be taken in up to 60 participants on two separate occasions separated by at least 6 weeks. Participants will complete all assessments, one baseline measurement obtained at sea level (0 - 300 m) and then twice during three-night acclimatization periods at Barcroft Station (3,801 m). At high altitude, participants will receive a treatment (placebo or SLAB51) upon arrival at Barcroft Station and then three times a day until departure from the high-altitude site. During the second portion of the study approximately six weeks later, participants will complete the same repeat assessments during a second three-night visit at Barcroft Station, where they will receive whichever treatment was not taken during the high-altitude exposure six weeks prior. Both participants and researchers performing the studies will be blinded to the treatment. Upon completion of the study, researchers will compare how participants acclimatized when they received SLAB51 versus when they received the placebo treatment.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Bishop, California, United States, 93514
      • White Mountain Research Station
    • La Jolla, California, United States, 92093
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form. Participants must have the cognitive ability to consent to participate in this study.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Persons aged ≥ 18 years old or ≤ 65 years old.
• Women and men will be studied.
• We will recruit healthy participants, in good general health evidenced by medical history.
• Pregnancy test will be done previous to the beginning of the study. No other specific laboratory tests will be performed before the study.
• In the case of participants that can get pregnant, we ask them to use effective contraception at least 1 month previous to the beginning of the first trip, and in between the first and the second trip.
• Ability to take oral medication and be willing to adhere to the SLAB51 regimen.

Exclusion Criteria:

• No exclusion criteria based on languages spoken.
• No exclusion will be based on gender, race, socioeconomic status.
• History of cardiovascular or pulmonary disease, including HAPE and HACE.
• Female's menstrual phase and use of birth control pills will be documented, as hormones are reported to influence the control of breathing (Regensteiner et al. 1989). However, women under birth control will not be excluded from the study. Pregnant females will be excluded.
• Current smoker or tobacco use (more than 1 cigarette per day).
• Presence of systemic or local infection.
• Patients with history of chronic cardiac, pulmonary, renal, liver, neurological, or psychiatric disease (except controlled mood disorders), i.e., failure to achieve SaO2 > 95% when breathing supplemental oxygen (inspired PO2 = 200-225 mmHg, equivalent to 30% O2 at sea level).
• Cases of acute pancreatitis and acute hypersensitivity to gluten and lactose.
• Immunosuppressed patients.
• Participants with a BMI higher than 35.
• Participants will be asked to answer a survey (STOP-BANG Score for Obstructive Sleep Apnea, https://www.mdcalc.com/calc/3992/stop-bang-score-obstructive-sleep-apnea) to determine self-reported OSA. Patients with a STOP-Bang Score higher equal or higher than 3 will be excluded.
• Use of any medications or agents that might interfere with the physiological measurements, such as ventilation and heart rate, will result in exclusion from our study, such as ibuprofen, anti-hypertensives, benzodiazepines, sleep aids including melatonin, opioids, other narcotics/sedatives and acetazolamide.
• Participants must not have traveled above 2,500 m (8,202 feet) of elevation for 4 weeks prior to the initial baseline measurement at sea level and throughout the duration of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic group; SLAB51 will be administered orally each day during the four days at high altitude. Each dose of SLAB51 consists of one six-gram sachet dissolved in 100 mL of water, containing approximately 800 billion bacteria. Participants will receive, in one of their trips, one dose of SLAB51 after arrival to high altitude, then three times a day approximately every 5 hours upon waking during Days 2 and 3, and a final dose the morning of Day 4 of acclimatization.	Dietary supplement: SLAB51; One dose of SLAB51 is administered after arrival to high altitude, then three times a day approximately every 5 hours upon waking during Days 2 and 3, and a final dose the morning of Day 4 of acclimatization.; Other Names: Oxxyslab
Placebo Comparator: Placebo group; Placebo will be administered in the other trip, following the same schedule as SLAB51 as described above.	Dietary supplement: SLAB51; One dose of SLAB51 is administered after arrival to high altitude, then three times a day approximately every 5 hours upon waking during Days 2 and 3, and a final dose the morning of Day 4 of acclimatization.; Other Names: Oxxyslab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygen saturation	The effects of treatment group (probiotic or placebo) and timepoint on daytime SpO2 and mean nocturnal SpO2 will be determined by two-way analysis of variance (ANOVA) with a Bonferroni post hoc test.	At sea level (one day, one night) and all four days and three nights of the study at high altitude

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoxic ventilatory response	Changes in ventilation due to the decrease of oxygen saturation (10%) and/or increase in carbon dioxide (5mmHg)	At sea level (one day) and one day at high altitude
Heart rate	Heart rate measurement	At sea level (one day, one night) and all four days at high altitude
Heart rate variability	Values of high frequency-low frequency ratio (HF/LF) of volunteers administered with SLAB51	At sea level (one day, one night) and all four days at high altitude
Blood pressure	Blood pressure measurement	At sea level (one day, one night) and all four days at high altitude
Sleep oxygen saturation	Oxygen levels during sleep	At sea level (one night) and all three nights of the study at high altitude
Sleep apnea hypopnea index	Number of times breathing stops and leads to a decrease of 3% oxygen saturation	At sea level (one night) and all three nights of the study at high altitude
Sleep oxygen desaturation index	How often and how much a person's blood oxygen saturation drops (at least 4%) during sleep	At sea level (one night) and all three nights of the study at high altitude
Sleep duration	How many hours and minutes a person sleeps during the night	At sea level (one night) and all three nights of the study at high altitude
Cancellation Pictures cognitive test	A timed, tablet-based test of selective attention and inhibitory control	Two consecutive days at sea level, each of the four days at high altitude, and another time at sea level 1-2 weeks after returning from high altitude.
Contrast Sensitivity cognitive test	Measures the ability to distinguish between fine increments of light and dark (contrast)	Two consecutive days at sea level, each of the four days at high altitude, and another time at sea level 1-2 weeks after returning from high altitude.
Digits-in-Noise cognitive test	Presents trials of three sequential spoken digits against a broad-band, speech-shaped masker. The outcome measure is the threshold noise tolerance.	Two consecutive days at sea level, each of the four days at high altitude, and another time at sea level 1-2 weeks after returning from high altitude.
Spatial Release from Masking cognitive test	Tests the ability to distinguish speech from competing speech using headphones and virtual spatial locations.	Two consecutive days at sea level, each of the four days at high altitude, and another time at sea level 1-2 weeks after returning from high altitude.
Trail Making cognitive test	A measure of visual attention and task switching ability with outcome measures of response time and accuracy.	Two consecutive days at sea level, each of the four days at high altitude, and another time at sea level 1-2 weeks after returning from high altitude.
Oxygen saturation in submaximal exercise	Measurement of oxygen saturation during the final 30 seconds of submaximal exercise on a stationary bike	At sea level (one day) and one day at high altitude
Lactate following submaximal exercise	Measurements of lactate following submaximal exercise on a stationary bike	At sea level (one day) and one day at high altitude
Acute Mountain Sickness Score	Questionnaire to gauge how a person feels at high altitude. It defines AMS as the presence of headaches in addition to three other symptoms, including gastrointestinal symptoms, fatigue/weakness, and dizziness/lightheadedness. Each symptom is appointed a point on a scale from 0 to 3, with 0 being no effect and 3 being severe. A total score of 3 or greater, with the presence of headaches, in a setting of rapid ascent to high altitude, is diagnosed as acute mountain sickness.	At sea level (one day) and all four days of the study at high altitude

Collaborators and Investigators

• Sponsor: University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: August 9, 2024
• First Posted (Actual): August 14, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 807971

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Although general information of mean and standard error data will be indicated in the graphs used for this project, individual data will be shown in as dots in the exposed graphs, and in tables when this is not possible.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No