Clinical trial NCT05289310: Low Oxygen Exposure and Weight Status
Official title: Effects of Daily Low Oxygen Exposure on Weight Status, Body Composition, and Metabolic Health
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity
Keywords: Body weight
Normobaric hypoxia
Negative energy balance
Energy intake
Energy expenditure
Lead sponsor: Pennington Biomedical Research Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2022-03-21
Enrollment: 60
Sex: ALL
Minimum age (years): 22
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the proposed double-blind, parallel-arm, randomized clinical trial is to evaluate changes in body weight and composition, assess determinants of energy balance (intake and expenditure), and measure modulators of energy balance, following 8 wk of calorie restriction (-500 kcal/d) in combination with either overnight exposure to normobaric hypoxia (8 h/night, 15% FiO2, \~2640 m) or normoxia (8 h/night, 21% FiO2), using a commercially available, in-home tent system, in adults with obesity.

Detailed description: Obesity and associated metabolic conditions are a significant public health burden, costing the U.S. \~$150 billion annually. Obesity is both a disease, affecting 1 in 3 Americans, and a risk factor for other chronic diseases, such as cardiovascular disease, type 2 diabetes, and 13 forms of cancers. Diet and exercise are the cornerstone of obesity prevention and treatment. However, a considerable number of individuals are non-responsive to existing weight-loss interventions and obesity rates continue to rise. Therefore, non-conventional approaches are needed to supplement current weight-loss strategies. Daily exposure to low-oxygen conditions may aid in current weight- loss strategies. Moderate (1500-3500 m) and higher (≥ 3500 m) altitude environments are naturally hypoxic due to the lower atmospheric pressure (for reference, Denver, CO is \~1600 m and Mt. Hood in Oregon is \~3500 m). Studies show that sea-level natives exposed to moderate- or high- altitude continuously for 5 or more days lose weight, which is a consequence of prolonged reductions in blood and tissue oxygenation that lead to increased energy expenditure and decreased appetite. However, implementation of hypoxia as a means for weight loss has been limited, to date, by the logistical constraints of traveling to remote locations or access to an altitude chamber. A safe, less expensive, and more logistically feasible alternative is the use of commercially available, low-oxygen systems at sea level, which create a normobaric hypoxic environment. Whether in-home, overnight, normobaric hypoxic exposure, compared to normobaric normoxic exposure, promotes body mass loss in adults with obesity remains unknown. Furthermore, determinants of energy balance, including energy intake and expenditure, and their relative contribution to normobaric hypoxia-induced weight loss have not been investigated. The objective of the proposed double-blind, parallel-arm, randomized clinical trial is to evaluate changes in body weight and composition, assess determinants of energy balance (intake and expenditure), and measure modulators of energy balance, following 8 wk of calorie restriction (-500 kcal/d) in combination with either overnight exposure to normobaric hypoxia (8 h/night, 15% FiO2, \~2640 m) or normoxia (8 h/night, 21% FiO2), using a commercially available, in-home tent system, in adults with obesity. Chronic (8 weeks), overnight (8 hours/night) low oxygen exposure may provide a non-conventional approach to supplement current weight-loss strategies, inform new strategies to accelerate weight loss, aid long-term weight management efforts, and benefit metabolic health in individuals with obesity.

Eligibility criteria: Inclusion Criteria:

* Obese (BMI between 30-39.9 kg/m2)
* Born at altitudes below 2,100 meters (\~7,000 feet)
* Currently residing in Tallahassee, Florida or surrounding area
* Completed a full FDA authorized or approved COVID-19 vaccination series at least 14 days before any in-person human research activity.
* Not taking any medication(s) that interfere with oxygen delivery/transport for 4 weeks prior to and throughout the entire study (e.g., includes sedatives, sleeping aids, tranquilizers and/or any medication that depresses ventilation, diuretics, alpha and beta blockers).
* Willing to refrain from smoking, vaping, chewing tobacco, and dietary supplement use throughout the entire study.
* Willing to have a hypoxic tent set-up in their home and spend 8 consecutive hours per night in the tent for 8 weeks
* Lives with a family member, partner/spouse, or roommate who can hear and respond in the unlikely event that the blood oxygen, air oxygen, or air carbon dioxide monitoring alarm would sound.

Exclusion Criteria:

* Living in areas that are more than 1,200 m (\~4,000 feet), or have traveled to areas that are more than 1,200 m for five days or more within the last 2 months
* Individuals who have not completed a full FDA authorized or approved COVID-19 vaccination series at least 14 days before any in-person human research activity.
* Cardiovascular abnormalities, gastrointestinal disorders, or any condition that interferes with oxygen delivery/transport (e.g., kidney disease, cardiovascular disease, etc.)
* Oxygen saturation \< 95% while awake or oxygen saturation dips below 88% for a total of ≥ 10 min overnight in normoxic conditions
* Evidence of apnea or other sleeping disorders
* Evidence of prior high-altitude pulmonary edema (HAPE) or high-altitude cerebral edema (HACE) diagnosis
* Diagnosis or family history of sickle cell anemia/trait
* Hematocrit \<42% for males, \<36% for females
* Hemoglobin \<13 g/dL for males, \<12 g/dL for females
* Blood donation within 8 weeks of beginning the study
* Present condition of alcoholism, anabolic steroids, or other substance abuse issues
* Women who are pregnant, lactating, planning to become pregnant, or who have had an irregular menstrual cycle in the past 6 mo.
* Weight gain or loss \> 10% of body weight during the past 6 months
* Adults unable to consent

Primary outcomes:
measure: Change in body weight
timeFrame: 10 weeks (70 days)
Secondary outcomes:
measure: 4-compartment body composition using DEXA and deuterium dilution
timeFrame: Days -7 and 49
measure: Waist circumference
timeFrame: Days -7 and 49
measure: Blood volume
timeFrame: Days -7 and 49
measure: Total daily energy expenditure (TDEE)
timeFrame: Days -7 to 0 and 49-56
measure: Resting metabolic rate
timeFrame: Days 0 and 56
measure: Resting substrate oxidation
timeFrame: Days 0 and 56
measure: Ad libitum energy intake
timeFrame: Days 0 and 56
measure: Subjective appetite measures
timeFrame: Days 0 and 56
measure: Overnight oxygen saturation (wrist-worn device)
timeFrame: 10 weeks (70 days)
measure: Overnight oxygen saturation (index finger pulse oximetry)
timeFrame: 10 weeks (70 days)
measure: Prevalence of acute mountain sickness
timeFrame: Days 0-7, 14, 21, 28, 35, 42, and 56
measure: Heart rate variability
timeFrame: Days 0 and 56
measure: Heart rate variability
timeFrame: 10 weeks (70 days)
measure: Urinary epinephrine
timeFrame: Days -1, 13, and 55
measure: Urinary norepinephrine
timeFrame: Days -1, 13, and 55
measure: Urinary dopamine
timeFrame: Days -1, 13, and 55
measure: Plasma glucose concentrations
timeFrame: Days 0 and 56
measure: Plasma insulin concentrations
timeFrame: Days 0 and 56
measure: Whole-body insulin sensitivity index
timeFrame: Days 0 and 56
measure: Thermic effect of glucose
timeFrame: Days 0 and 56
measure: 24-hour continuous glucose concentrations
timeFrame: Days -14-0, 1-14, and 42-56
measure: 24-hour glucose variability
timeFrame: Days -14-0, 1-14, and 42-56
measure: Assessment of sleep
timeFrame: 10 weeks (70 days)
measure: Pittsburgh Sleep Quality Index
timeFrame: Days -1, 14, and 56
measure: Subjective sleep quality
timeFrame: Days -7-0, 1-14, and 49-56
measure: Fasting measures of iron status
timeFrame: Days 0 and 56
measure: Psychosocial Factors
timeFrame: Days 0, 14, and 56
measure: Fasting blood pressure
timeFrame: Days -7 and 49
measure: Barrier Questionnaire
timeFrame: Day 56
measure: Change in body weight
timeFrame: 4 weeks after intervention ends
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
Study officials:
affiliation: Pennington Biomedical Research Center
name: Claire E. Berryman, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References: