Intermittent Hypoxia-hyperoxia Therapy in Obese Patients (IHHTOP)

Obesity Clinical Trial

— (IHHTOP)  

Official title:

The Metabolic and Respiratory Effects of Intermittent Hypoxia-hyperoxia Therapy in Obese Patients Within the Complex Management of Medical Rehabilitation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06451601
• Other study ID #: AndreeaUzun
• Status: Completed
• Phase: N/A
• Start date: April 1, 2024
• Est. completion date: May 15, 2024

Study information

• Verified date: June 2024
• Source: Balnear and Rehabilitation Sanatorium Techirghiol
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Obesity represents the excessive or abnormal accumulation of adipose tissue in the body, which affects health through its association with the risk of developing diabetes mellitus, cardiovascular and pulmonary diseases and hypertension. Obesity can cause significant respiratory changes, so obese patients present pulmonary complications more frequently than individuals with normal weight. Intermittent hypoxia (IH) represents the alternation between repeated episodes of hypoxia interspersed with normoxic episodes. Intermittent hypoxia-hyperoxia is the therapy that uses hyperoxic intervals instead of normoxic ones between hypoxic breathing sessions. This study aimed to evaluate the effectiveness of intermittent hypoxia-hyperoxia therapy among obese patients, focusing on metabolic and respiratory effects. The study aimed to determine if this method could bring benefits in managing or alleviating the complications associated with obesity. A total of 70 obese patients will be recruited and randomized to either the IHHT group or the control group. The intervention group will receive IHHT while the control group will not receive this therapy. All patients will be assessed at baseline and after 2 weeks of treatment using a variety of clinical and functional measures. The study's results will be used to determine whether IHHT benefits the patients who follow it. This study is designed to contribute to the existing body of knowledge on treating obese patients. The results of the study will be of interest to clinicians, researchers, and patients.

Description:

The study was a prospective, randomized controlled, unicentric study conducted at the Balneal and Rehabilitation Sanatorium Techirghiol (BRST) in Romania. A total of 70 obese patients (BMI > 30 kg/m2) were enrolled in the study. The patients were randomly assigned to either the IHHT group or the control group. Patients in the intervention group received intermittent hypoxia-hyperoxia therapy and patients in the control group did not receive this therapy. Simultaneously with the intermittent hypoxia-hyperoxia therapy, the patients benefited from complex balneo-physical-kinetic treatment which included hydrokinetotherapy and hydrothermotherapy using specific natural environmental factors: sapropelic mud and salt water from Lake Techirghiol, electrotherapy, massage therapy and kinetotherapy. The 35 patients in the IHHT group underwent intermittent hypoxia-hyperoxia therapy using the CellOxy Device. During the hypoxic phases, patients received concentrations of 9-16% O2, while during the hyperoxic phases, approximately 35% O2 was administered. During both testing and actual therapy sessions, patients remained in a comfortable position, lying on a bed. Initially, patients performed hypoxic tests 1 and 2, to determine the optimal oxygen level and to be included in a typology (type I, II, or III). Based on the obtained data, the device automatically calculated and planned personalized IHHT sessions for each patient. Starting from the following day, patients in the IHHT group were subjected to intermittent hypoxia-hyperoxia as follows: hypoxia with 9-16% O2 for 5-7 minutes, followed by exposure to hyperoxia with ~35% O2 for 2-5 minutes. During the sessions, both SpO2 and heart rate were constantly monitored using the device's built-in pulse oximeter. In total, patients in the IHHT group performed 9 sessions of hypoxic-hyperoxic therapy: testing on the first day (hypoxic tests 1 and 2), followed by 4 days of sessions in the first week, 2 days of rest on the weekend and then another 5 days of sessions in the second week. The initial assessment of patients consisted of a comprehensive medical examination, which identified their comorbidities, family history, verification of medication for associated pathologies and behavioral factors (smoking, alcohol consumption, psychosocial stress). All patients underwent the following measurements: resting blood pressure (BP), heart rate (HR), blood oxygen saturation (SpO2), anthropometric data: height (cm), body weight (kg), waist circumference (cm), and hip circumference (cm), BMI calculation, blood sampling (urea, uric acid, creatinine, glucose, total cholesterol, AST, ALT). Regardless of the presence or absence of changes in the analysis results, patients were included in the study. We consider it important to investigate the entire spectrum of the studied patients, including those with evident changes in their analyses and those with normal results, to obtain a comprehensive and representative image of the researched phenomenon. The patients also performed a 6-minute walk test and a spirometry. After completing the 2 weeks of treatment at the Balneal and Rehabilitation Sanatorium of Techirghiol, the final assessment identified the same parameters as followed initially. The statistical analysis was performed using IBM SPSS statistics software version 25. Data are presented as mean ± standard deviation (SD) for continuous variables in case of symmetric distributions, median and IQR (Interquartile range IQR = P75-P25) for numerical discrete variables or for continuous variables in case of skewed distributions, or as frequencies and percentages for categorical variables. The normality of the continuous data was estimated with Shapiro-Wilk Tests of Normality. For hypotheses testing: Independent Samples Mann Whitney U test, Related Samples Wilcoxon Signed Rank Test, Chi-Square Test of association, were used depending on the type of analyzed variables. Spearman's correlation coefficient was used as a statistical measure of the strength of a relationship between paired data. The significance level α was set at 0.05. If the test statistic for every conducted test was in the critical region, and the p-value was less than or equal to the significance level, we decided to reject the null hypothesis in favor of the alternative hypothesis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: May 15, 2024
• Est. primary completion date: May 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• patients with BMI >30 kg/m2
• aged between 40-75 years
• patients to sign the informed consent form
• patients to be compensated and to have medical treatment for associated pathologies

Exclusion Criteria:

• BMI <30 kg/m2
• age under 40 or over 75 years
• refusal to sign the informed consent form
• patients presenting contraindications to intermittent hypoxia-hyperoxia therapy
• patients presenting contraindications to complex medical rehabilitation treatment

Related Conditions & MeSH terms

• Hyperoxia
• Hypoxia
• Obesity

Intervention

Device:
• Intermittent hypoxia-hyperoxia therapy
Data on demographics and clinical conditions was gathered. The investigators collect the next features: sex, age, occupation, environment, body mass index, nutritional status, abdominal circumference, hip circumference, smoking, alcohol. Also, the patients performed a 6-minute walking test. Other Names: Hydrokinetotherapy Hydrothermotherapy Electrotherapy Massage therapy Kinetotherapy

Locations

Country	Name	City	State
Romania	Balneal and Rehabilitation Sanatorium Techirghio	Techirghiol	Constanta

Sponsors (1)

Lead Sponsor	Collaborator
Balnear and Rehabilitation Sanatorium Techirghiol

Country where clinical trial is conducted

Romania, 

References & Publications (30)

Afina AB, Oleg SG, Alexander AB, Ines D, Alexander Yu S, Nikita VV, Denis ST, Daria GG, Zhang Y, Chavdar SP, Dmitriy VG, Elena AS, Irina VK, Philippe Yu K. The Effects of Intermittent Hypoxic-Hyperoxic Exposures on Lipid Profile and Inflammation in Patients With Metabolic Syndrome. Front Cardiovasc Med. 2021 Aug 27;8:700826. doi: 10.3389/fcvm.2021.700826. eCollection 2021. — View Citation

Bayer U, Glazachev OS, Likar R, Burtscher M, Kofler W, Pinter G, Stettner H, Demschar S, Trummer B, Neuwersch S. [Adaptation to intermittent hypoxia-hyperoxia improves cognitive performance and exercise tolerance in elderly]. Adv Gerontol. 2017;30(2):255-261. Russian. — View Citation

Behrendt T, Bielitzki R, Behrens M, Herold F, Schega L. Effects of Intermittent Hypoxia-Hyperoxia on Performance- and Health-Related Outcomes in Humans: A Systematic Review. Sports Med Open. 2022 May 31;8(1):70. doi: 10.1186/s40798-022-00450-x. — View Citation

Bestavashvili A, Glazachev O, Ibragimova S, Suvorov A, Bestavasvili A, Ibraimov S, Zhang X, Zhang Y, Pavlov C, Syrkina E, Syrkin A, Kopylov P. Impact of Hypoxia-Hyperoxia Exposures on Cardiometabolic Risk Factors and TMAO Levels in Patients with Metabolic Syndrome. Int J Mol Sci. 2023 Sep 24;24(19):14498. doi: 10.3390/ijms241914498. — View Citation

Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med. 2007 Apr 1;175(7):661-6. doi: 10.1164/rccm.200611-1717OC. Epub 2007 Jan 18. — View Citation

Bischoff SC, Schweinlin A. Obesity therapy. Clin Nutr ESPEN. 2020 Aug;38:9-18. doi: 10.1016/j.clnesp.2020.04.013. Epub 2020 May 11. — View Citation

Burtscher M, Gatterer H, Szubski C, Pierantozzi E, Faulhaber M. Effects of interval hypoxia on exercise tolerance: special focus on patients with CAD or COPD. Sleep Breath. 2010 Sep;14(3):209-20. doi: 10.1007/s11325-009-0289-8. Epub 2009 Aug 18. — View Citation

Collins LC, Hoberty PD, Walker JF, Fletcher EC, Peiris AN. The effect of body fat distribution on pulmonary function tests. Chest. 1995 May;107(5):1298-302. doi: 10.1378/chest.107.5.1298. — View Citation

Cortes-Telles A, Ortiz-Farias DL, Pou-Aguilar YN, Almeida-de-la-Cruz L, Perez-Padilla JR. Clinical impact of obesity on respiratory diseases: A real-life study. Lung India. 2021 Jul-Aug;38(4):321-325. doi: 10.4103/lungindia.lungindia_701_20. — View Citation

Costalat G, Lemaitre F, Tobin B, Renshaw G. Intermittent hypoxia revisited: a promising non-pharmaceutical strategy to reduce cardio-metabolic risk factors? Sleep Breath. 2018 Mar;22(1):267-271. doi: 10.1007/s11325-017-1459-8. Epub 2017 Feb 2. — View Citation

Dixon AE, Peters U. The effect of obesity on lung function. Expert Rev Respir Med. 2018 Sep;12(9):755-767. doi: 10.1080/17476348.2018.1506331. Epub 2018 Aug 14. — View Citation

Dudnik E, Zagaynaya E, Glazachev OS, Susta D. Intermittent Hypoxia-Hyperoxia Conditioning Improves Cardiorespiratory Fitness in Older Comorbid Cardiac Outpatients Without Hematological Changes: A Randomized Controlled Trial. High Alt Med Biol. 2018 Dec;19(4):339-343. doi: 10.1089/ham.2018.0014. Epub 2018 Sep 22. — View Citation

Ford ES, Cunningham TJ, Mercado CI. Lung function and metabolic syndrome: Findings of National Health and Nutrition Examination Survey 2007-2010. J Diabetes. 2014 Nov;6(6):603-13. doi: 10.1111/1753-0407.12136. — View Citation

Glazachev O, Kopylov P, Susta D, Dudnik E, Zagaynaya E. Adaptations following an intermittent hypoxia-hyperoxia training in coronary artery disease patients: a controlled study. Clin Cardiol. 2017 Jun;40(6):370-376. doi: 10.1002/clc.22670. Epub 2017 Mar 21. — View Citation

Glazachev OS, Zvenigorodskaia LA, Dudnik EN, Iartseva LA, Mishchenkova TV, Platonenko AV, Spirina GK. [Interval hypoxic-hyperoxic training in the treatment of the metabolic syndrome]. Eksp Klin Gastroenterol. 2010;(7):51-6. Russian. — View Citation

Glazychev OS. [Optimization of clinical application of interval hypoxic training]. Med Tekh. 2013 May-Jun;(3):21-4. No abstract available. Russian. — View Citation

Hegewald MJ. Impact of obesity on pulmonary function: current understanding and knowledge gaps. Curr Opin Pulm Med. 2021 Mar 1;27(2):132-140. doi: 10.1097/MCP.0000000000000754. — View Citation

https://www.cell-oxy.com/thedevice

Iliescu MG, Stanciu LE, Uzun AB, Cristea AE, Motoasca I, Irsay L, Iliescu DM, Vari T, Ciubean AD, Caraban BM, Ciufu N, Azis O, Ciortea VM. Assessment of Integrative Therapeutic Methods for Improving the Quality of Life and Functioning in Cancer Patients-A Systematic Review. J Clin Med. 2024 Feb 20;13(5):1190. doi: 10.3390/jcm13051190. — View Citation

Irsay L, Ungur RA, Borda IM, Tica I, Iliescu MG, Ciubean AD, Popa T, Cinteza D, Popa FL, Bondor CI, Ciortea VM. Safety of Electrotherapy Treatment in Patients with Knee Osteoarthritis and Cardiac Diseases. Life (Basel). 2022 Oct 24;12(11):1690. doi: 10.3390/life12111690. — View Citation

Lin X, Li H. Obesity: Epidemiology, Pathophysiology, and Therapeutics. Front Endocrinol (Lausanne). 2021 Sep 6;12:706978. doi: 10.3389/fendo.2021.706978. eCollection 2021. — View Citation

Mallet R, Burtcher J, Manukhina E, Downy F, Glazachev O, Serebrovskaya T, et al. Hypoxic-hyperoxic conditioning and demen-tia. Diagn Manage Dement. (2020) 47:745-60. 10.1016/B978-0-12-815854-8.00047-1

Murugan AT, Sharma G. Obesity and respiratory diseases. Chron Respir Dis. 2008;5(4):233-42. doi: 10.1177/1479972308096978. — View Citation

Panuganti KK, Nguyen M, Kshirsagar RK. Obesity. 2023 Aug 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK459357/ — View Citation

Serebrovska ZO, Serebrovska TV, Kholin VA, Tumanovska LV, Shysh AM, Pashevin DA, Goncharov SV, Stroy D, Grib ON, Shatylo VB, Bachinskaya NY, Egorov E, Xi L, Dosenko VE. Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer's Disease in Patients with Mild Cognitive Impairment: A Pilot Study. Int J Mol Sci. 2019 Oct 30;20(21):5405. doi: 10.3390/ijms20215405. — View Citation

Serebrovskaya TV, Xi L. Intermittent hypoxia training as non-pharmacologic therapy for cardiovascular diseases: Practical analysis on methods and equipment. Exp Biol Med (Maywood). 2016 Sep;241(15):1708-23. doi: 10.1177/1535370216657614. Epub 2016 Jul 12. — View Citation

Thompson WG, Cook DA, Clark MM, Bardia A, Levine JA. Treatment of obesity. Mayo Clin Proc. 2007 Jan;82(1):93-101; quiz 101-2. doi: 10.4065/82.1.93. — View Citation

Ungur RA, Ciortea VM, Irsay L, Ciubean AD, Nasui BA, Codea RA, Singurean VE, Groza OB, Cainap S, Martis Petrut GS, Borda C, Borda IM. Can Ultrasound Therapy Be an Environmental-Friendly Alternative to Non-Steroidal Anti-Inflammatory Drugs in Knee Osteoarthritis Treatment? Materials (Basel). 2021 May 21;14(11):2715. doi: 10.3390/ma14112715. — View Citation

Uzun AB, Iliescu MG, Stanciu LE, Ionescu EV, Ungur RA, Ciortea VM, Irsay L, Motoasca I, Popescu MN, Popa FL, Pazara L, Tofolean DE. Effectiveness of Intermittent Hypoxia-Hyperoxia Therapy in Different Pathologies with Possible Metabolic Implications. Metabolites. 2023 Jan 25;13(2):181. doi: 10.3390/metabo13020181. — View Citation

Zammit C, Liddicoat H, Moonsie I, Makker H. Obesity and respiratory diseases. Int J Gen Med. 2010 Oct 20;3:335-43. doi: 10.2147/IJGM.S11926. — View Citation

* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metabolic effects	Blood sampling (urea, uric acid, creatinine, glucose, total cholesterol). The Units of Measure for these biomarkers = mg/dL.	Two measurements, at the beginning of treatment and after 2 weeks of treatment.
Primary	Metabolic effects	Blood sampling (AST, ALT). The Units of Measure for these biomarkers = U/L.	Two measurements, at the beginning of treatment and after 2 weeks of treatment.
Secondary	Respiratory effects	Spirometry (FVC, FEV1). The Units of Measure = l.	Two measurements, at the beginning of treatment and after 2 weeks of treatment.
Secondary	Respiratory effects	Spirometry (FEV1/FVC ). The Units of Measure = %.	Two measurements, at the beginning of treatment and after 2 weeks of treatment.