Effects of Short and Long Courses of Intermittent Hypoxic-Hyperoxic Training in Patients With Type 2 Diabetes Including Elderly

Official title

A Single-Center Randomized Clinical Trial With Prospective Follow-up of the Efficacy and Safety of Short and Long Duration Intermittent Hypoxic-Hyperoxic Training in Patients With Type 2 Diabetes Mellitus Including Elderly Patients

Overview

This is a single-center randomized controlled trial evaluating the efficacy and safety of short (3 days) versus long (10 days) courses of intermittent hypoxic-hyperoxic training (IHHT) in patients with type 2 diabetes mellitus aged 50-74 years. Participants will be randomized into three groups: 3-day IHHT course (n≥100), 10-day IHHT course (n≥100), or control group receiving gas mixture with constant O2 21% for 10 days (n≥50). The primary outcomes are fasting glucose levels and HbA1c. Secondary outcomes include cardiovascular parameters, quality of life, cognitive function, and biological age.

Interventions

• Other Intermittent Hypoxic-Hyperoxic Training (3 days)
  Three daily sessions using HYPO-OXY-1 (OXYTERRA) device
• Other Intermittent Hypoxic-Hyperoxic Training (10 days)
  Ten daily sessions using HYPO-OXY-1 (OXYTERRA) device
• Other Normoxic gas breathing
  Ten daily sessions of breathing gas mixture with constant O2 21%

Primary outcome measures

• Change in fasting glucose level (mmol/L) from baseline to 30±3 days after intervention completion [Time frame: Baseline, day 30]
• Change in HbA1c (%) from baseline to 30±3 days after intervention completion [Time frame: Baseline, day 30]

Secondary outcome measures (8)

• Change in Cardio-Ankle Vascular Index (CAVI) [Time frame: Baseline, day 17-19, day 30]
• Change in flow-mediated vasodilation (%) [Time frame: Baseline, day 17-19, day 30 post-intervention]
• Change in 24-hour ambulatory blood pressure [Time frame: Baseline and 30±3 days post-intervention]
• Change in quality of life by SF-36 [Time frame: Baseline, day 17-19, and 30±3 days post-intervention]
• Change in cognitive function by MoCA scale [Time frame: Baseline, day 17-19, and 30±3 days post-intervention]
• Change in anxiety and depression by HADS [Time frame: Baseline, day 17-19, and 30±3 days post-intervention]
• Change in biological age [Time frame: Baseline and 30±3 days post-intervention]
• Change in 6-minute walk test distance (meters) [Time frame: Baseline and 30±3 days post-intervention]

Eligibility criteria

Inclusion criteria

• Age 50-74 years inclusive
• Type 2 diabetes mellitus confirmed by medical documentation
• Stable therapy for diabetes and other chronic diseases for at least 4 weeks prior to enrollment
• Ability to comply with study protocol requirements
• Signed informed consent

Exclusion criteria

• Type 1 diabetes mellitus
• Acute diabetes complications within 6 months (diabetic ketoacidosis, hyperosmolar hyperglycemic state, lactic acidosis, hypoglycemic coma)
• Acute or active chronic infections
• Angina pectoris functional class III-IV
• Uncontrolled grade 3 arterial hypertension (SBP ≥180 and/or DBP ≥110 mmHg)
• Acute cerebrovascular accident, myocardial infarction, surgical interventions, clinically significant injuries within 6 months
• Internal carotid artery stenosis >60% and/or symptomatic stenosis 50-99%
• Chronic obstructive pulmonary disease and bronchial asthma
• Exacerbation and decompensation of chronic diseases within 1 month ALT and/or AST levels >2-3 times upper limit of normal
• Congenital heart and major vessel abnormalities
• Implanted cardiac pacemaker
• Cancer with remission <5 years
• Mental illness, drug addiction, alcohol dependence
• Pregnancy
• Inability to participate throughout the study period

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Russia · 1 center

• National Medical Research Center for Therapy and Preventive Medicine — Moscow

Publications

• Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, McCormack MC, Carlin BW, Sciurba FC, Pitta F, Wanger J, MacIntyre N, Kaminsky DA, Culver BH, Revill SM, Hernandes NA, Andrianopoulos V, Camillo CA, Mitchell KE, Lee AL, Hill CJ, Singh SJ. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir PMID 25359355
• Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, Hou L, Baccarelli AA, Stewart JD, Li Y, Whitsel EA, Wilson JG, Reiner AP, Aviv A, Lohman K, Liu Y, Ferrucci L, Horvath S. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018 Apr 18;10(4):573-591. doi: 10.18632/aging.101414. PMID 29676998
• Moore HM, Kelly A, Jewell SD, McShane LM, Clark DP, Greenspan R, Hainaut P, Hayes DF, Kim P, Mansfield E, Potapova O, Riegman P, Rubinstein Y, Seijo E, Somiari S, Watson P, Weier HU, Zhu C, Vaught J. Biospecimen Reporting for Improved Study Quality. Biopreserv Biobank. 2011 Apr;9(1):57-70. doi: 10.1089/bio.2010.0036. PMID 21826252
• Chernyavsky M.A., Irtyuga O.B., Yanishevsky S.N., Alieva A.S., Samochernykh K.A., Abramov K.B., Vavilova T.V., Lukyanchikov V.A., Kurapeev D.I., Vanyurkin A.G., Chernova D.V., Shelukhanov N.K., Kozlyonok А.V., Kavteladze Z.A., Malevanny M.V., Vinogradov R.A., Khafizov T.N., Ivanova G.E., Zhukovskaya N.V., Fokin A.A., Ignatiev I.M., Karpenko A.A., Ignatenko P.V., Astapov D.A., Semenov V.Yu., Porkha
• Dedov II, Shestakova MV, Sukhareva OY, editors. Standards of specialized diabetes care. 12th edition. Moscow; 2025
• Serebrovska TV, Grib ON, Portnichenko VI, Serebrovska ZO, Egorov E, Shatylo VB. Intermittent Hypoxia/Hyperoxia Versus Intermittent Hypoxia/Normoxia: Comparative Study in Prediabetes. High Alt Med Biol. 2019 Dec;20(4):383-391. doi: 10.1089/ham.2019.0053. Epub 2019 Oct 7. PMID 31589074

Identifiers

NCT: NCT07574333 · EFIR_0309_2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗