Low Oxygen Exposure for Obesity

(LOWS Trial)

Recruiting at 1 trial location

Overseen By Claire E. Berryman, PhD, RD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Florida State University

Must not be taking: Sedatives, Sleeping aids, Tranquilizers, others

Disqualifiers: Cardiovascular, Gastrointestinal, Kidney, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications that interfere with oxygen delivery or transport, such as sedatives, sleeping aids, tranquilizers, diuretics, and alpha or beta blockers, for 4 weeks before and throughout the study.

Is low oxygen exposure safe for humans?

The research does not provide specific safety data on low oxygen exposure for obesity, but it highlights potential risks of oxygen therapy in obese individuals, such as worsening breathing issues. This suggests that any oxygen-related treatment should be carefully monitored in this population. ^{1 2 3 4 5}

How does the treatment of normobaric hypoxia differ from other treatments for obesity?

Normobaric hypoxia (NH) is unique because it involves exposure to low oxygen levels, either at rest or combined with exercise, which can enhance weight loss and improve cardio-metabolic health in obese individuals. Unlike traditional treatments, NH can increase energy expenditure and reduce insulin levels without the need for dietary changes, making it a novel approach to managing obesity. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Low Oxygen Exposure for Obesity?

Research shows that training in low oxygen conditions (normobaric hypoxia) can lead to more weight loss in obese individuals compared to normal oxygen conditions. Additionally, this approach has been associated with improvements in energy expenditure and reductions in body weight and blood pressure, which may help manage obesity. ^{6 7 9 11 12}

Who Is on the Research Team?

Claire E. Berryman, PhD, RD

Principal Investigator

Pennington Biomedical Research Center

Are You a Good Fit for This Trial?

This trial is for adults with obesity (BMI between 30-39.9) in Tallahassee, Florida who don't smoke or use certain supplements and medications. They must have completed COVID-19 vaccination, live below ~7,000 feet altitude, and share a home with someone who can respond to safety alarms.

Inclusion Criteria

Currently residing in Tallahassee, Florida or surrounding area

Willing to refrain from smoking, vaping, chewing tobacco, and dietary supplement use throughout the entire study

My BMI is between 30 and 39.9.

Exclusion Criteria

I have been diagnosed with HAPE or HACE before.

Blood donation within 8 weeks of beginning the study

Weight gain or loss > 10% of body weight during the past 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Baseline measurements including body composition, blood volume, and fasting measures are taken

2 weeks

Multiple visits for baseline assessments

Treatment

Participants undergo 8 weeks of calorie restriction combined with either normobaric hypoxia or normoxia exposure

8 weeks

Daily overnight exposure (8 hours/night)

Follow-up

Participants are monitored for sustained weight loss and metabolic health

4 weeks

1 visit for follow-up assessment

What Are the Treatments Tested in This Trial?

Interventions

• Normobaric hypoxia (NH)
• Normobaric normoxia (NN)

Trial Overview The study tests if sleeping in a low-oxygen tent at home for 8 hours nightly over 8 weeks affects weight loss during calorie restriction. Participants are randomly assigned to breathe either normal air (NN) or lower oxygen levels (NH), mimicking high altitude.

How Is the Trial Designed?

Group I: Normobaric hypoxia (NH) Experimental Treatment 1 Intervention

8 weeks of overnight exposure (8 hrs/night) to NH conditions (\~15% oxygen; achieved with nitrogen dilution, equivalent to \~8500 feet elevation) using a commercially available tent and generator system (Hypoxico, Inc., New York, NY).

Group II: Normobaric normoxia (NN) Placebo Group 1 Intervention

8 weeks of overnight exposure (8 hrs/night) to NN conditions (\~21% oxygen; sea level) using a commercially available tent and generator system (Hypoxico, Inc., New York, NY).

Who Is Running the Clinical Trial?

Florida State University

Lead Sponsor

Trials

234

Recruited

41,100+

Pennington Biomedical Research Center

Lead Sponsor

Trials

314

Recruited

183,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 22 obese young adults over 4 weeks, those who underwent normobaric hypoxia training lost significantly more weight (-6.9 kg) compared to those who trained in normoxia (-4.3 kg), indicating that hypoxia training can enhance weight loss efforts.

Normobaric hypoxia training also led to significant improvements in systolic and mean blood pressure, suggesting additional cardiovascular benefits alongside weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normobaric hypoxia training causes more weight loss than normoxia training after a 4-week residential camp for obese young adults. Kong, Z., Zang, Y., Hu, Y.[2021]

Normobaric hypoxic conditioning (HC) has shown promising results in improving cardio-metabolic health in obese populations, with passive HC leading to significant reductions in insulin levels and increased energy expenditure in humans.

Active HC resulted in weight loss and lower blood pressure in both obese animals and humans, suggesting that this approach could be beneficial for weight management and overall health, although more research is needed to clarify its effects on other health markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normobaric hypoxic conditioning to maximize weight loss and ameliorate cardio-metabolic health in obese populations: a systematic review. Hobbins, L., Hunter, S., Gaoua, N., et al.[2020]

Oxygen availability is crucial in metabolic disorders like obesity, type 2 diabetes, and cardiovascular disease, suggesting that oxygen could be considered a nutrient essential for health.

Novel therapies, such as intermittent hypoxia training and hyperoxia, may offer new treatment options for metabolic disorders, highlighting the need for better methods to measure oxygen levels and understand their role in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen in Metabolic Dysfunction and Its Therapeutic Relevance. Lopez-Pascual, A., Trayhurn, P., Martínez, JA., et al.[2022]

In a study involving 32 obese participants, those who trained in mild hypoxia (15% O2) lost significantly more weight (1.14 kg) compared to those in a sham hypoxia group (0.03 kg) after 8 weeks of low-intensity exercise, indicating the potential efficacy of hypoxic training for weight loss.

The study, which was the first of its kind with a sham control, showed that mild hypoxic conditions can enhance weight loss without negatively affecting blood sugar levels, as HbA1C values remained stable throughout the training period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intense physical exercise in normobaric hypoxia leads to more weight loss in obese people than low intense physical exercise in normobaric sham hypoxia. Netzer, NC., Chytra, R., Küpper, T.[2023]

A study involving 12 males with overweight found that 60 minutes of hypoxic exposure at different oxygen levels did not improve glycaemic control or insulin sensitivity during an oral glucose tolerance test, indicating that hypoxia may not be beneficial for glucose metabolism in this population.

While lower oxygen levels (VHIGH) did lead to increased symptoms of dyspnoea and acute mountain sickness, they did not affect glucose levels, suggesting that higher levels of hypoxia may pose safety concerns without providing metabolic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of different levels of acute hypoxia on subsequent oral glucose tolerance in males with overweight: A balanced cross-over pilot feasibility study. Corbett, J., Tipton, MJ., Perissiou, M., et al.[2023]

In a study of 184 obese individuals with chronic hypoxemia, 80% were found to have obstructive sleep apnea (OSA) and 51% had obesity hypoventilation syndrome (OHS), indicating a high prevalence of these conditions in this population.

The study highlights that relying only on arterial blood gas measurements and pulmonary function tests is inadequate for diagnosing OSA and OHS, suggesting that further sleep testing is necessary to ensure safe and effective treatment options, especially before administering supplemental oxygen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Sleep-disordered Breathing in Obese Patients with Chronic Hypoxemia. A Cross-Sectional Study. Povitz, M., James, MT., Pendharkar, SR., et al.[2022]

In a randomized crossover trial involving 22 morbidly obese inpatients, high concentration oxygen therapy significantly increased transcutaneous carbon dioxide tension (Ptco2) by an average of 3.2 mmHg compared to titrated oxygen therapy.

The study supports clinical guidelines recommending that oxygen therapy for morbidly obese patients should be titrated to maintain peripheral oxygen saturation (Spo2) between 88-92% to avoid potential respiratory complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High flow or titrated oxygen for obese medical inpatients: a randomised crossover trial. Pilcher, J., Richards, M., Eastlake, L., et al.[2022]

In a study of 150 hospitalized patients with severe obesity, 31% were found to have hypoventilation, which is linked to higher rates of complications such as increased need for intensive care and mechanical ventilation.

Patients with obesity-associated hypoventilation had a significantly higher mortality rate of 23% over 18 months compared to 9% in those with simple obesity, highlighting the serious health risks associated with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Nowbar, S., Burkart, KM., Gonzales, R., et al.[2023]

In a study involving 28 participants (14 with obesity hypoventilation syndrome and 14 healthy controls), breathing moderate concentrations of supplemental oxygen (FiO2 0.28 and 0.50) led to significant increases in carbon dioxide levels (PavCO2) and acidaemia in individuals with obesity hypoventilation syndrome, indicating potential risks associated with this treatment.

The study found that while healthy controls did not experience changes in PavCO2 or pH with increased oxygen, those with obesity hypoventilation syndrome showed hypoventilation and increased physiological dead space, suggesting that oxygen therapy can be harmful in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate concentrations of supplemental oxygen worsen hypercapnia in obesity hypoventilation syndrome: a randomised crossover study. Hollier, CA., Harmer, AR., Maxwell, LJ., et al.[2014]

In a study of 50 morbidly obese patients, using the reverse Trendelenburg position with pressure support ventilation (RT/PPV) significantly increased the safe non-hypoxic apnea period (SNHAP) to 258.2 seconds compared to 216.7 seconds with the ramp position and zero end-expiratory pressure (RP/ZEEP).

The RT/PPV method also led to quicker achievement of optimal oxygen levels, with 88% of patients reaching a satisfactory end-tidal oxygen concentration of 0.90, and a faster recovery to 97% oxygen saturation after ventilation, highlighting its effectiveness in reducing hypoxemia risks during airway management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of reverse Trendelenburg position and positive pressure ventilation on safe non-hypoxic apnea period in obese, a randomized-control trial. Couture, EJ., Carrier-Boucher, A., Provencher, S., et al.[2023]

Normobaric hypoxia (NH) can be used as a practical substitute for hypobaric hypoxia (HH) in training and research by adjusting the inspired fraction of oxygen to match the oxygen partial pressure at high altitudes.

However, the physiological responses to NH and HH are not identical, as differences in alveolar gas composition arise due to nitrogen dilution effects, meaning that caution should be taken when interpreting results from NH as directly applicable to HH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalent Air Altitude and the Alveolar Gas Equation. Conkin, J.[2016]

Hypoxic training over 4 weeks improved glucose tolerance more significantly than normoxic training, despite no changes in overall fat mass or abdominal fat area in either group of 20 sedentary subjects.

Both training conditions led to reduced fasting glucose and insulin levels, but hypoxic training did not enhance the regulation of appetite-related hormones compared to normoxic training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole body, regional fat accumulation, and appetite-related hormonal response after hypoxic training. Morishima, T., Kurihara, T., Hamaoka, T., et al.[2018]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Normobaric hypoxia training causes more weight loss than normoxia training after a 4-week residential camp for obese young adults. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Normobaric hypoxic conditioning to maximize weight loss and ameliorate cardio-metabolic health in obese populations: a systematic review. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Oxygen in Metabolic Dysfunction and Its Therapeutic Relevance. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Low intense physical exercise in normobaric hypoxia leads to more weight loss in obese people than low intense physical exercise in normobaric sham hypoxia. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of different levels of acute hypoxia on subsequent oral glucose tolerance in males with overweight: A balanced cross-over pilot feasibility study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Prevalence of Sleep-disordered Breathing in Obese Patients with Chronic Hypoxemia. A Cross-Sectional Study. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

High flow or titrated oxygen for obese medical inpatients: a randomised crossover trial. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Moderate concentrations of supplemental oxygen worsen hypercapnia in obesity hypoventilation syndrome: a randomised crossover study. [2014]

10. England pubmed.ncbi.nlm.nih.gov

Effect of reverse Trendelenburg position and positive pressure ventilation on safe non-hypoxic apnea period in obese, a randomized-control trial. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Equivalent Air Altitude and the Alveolar Gas Equation. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Whole body, regional fat accumulation, and appetite-related hormonal response after hypoxic training. [2018]