Evaluation of the Effect of IHHT on Vascular Stiffness and Elasticity of the Liver Tissue in Patients With MS.

Double-Blind, Placebo-Controlled, Randomized Parallel Design Trial of Evaluation of the Effect of Interval Hypoxic-hyperoxic Training (IHHT) on Vascular Stiffness and Elasticity of the Liver Tissue in Patients With Metabolic Syndrome.

The aim of this study is to assess the effect of interval hypoxy-hyperoxic training (IHHT) on the arterial stiffness and elasticity of the liver tissue in patients with metabolic syndrome and on other components of the metabolic syndrome, and the possibility of their reversible recovery after training.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Vascular Stiffness; Liver Fibroses; Trimethylamine N-oxyde; Toll-like Receptors
• Intervention / Treatment: Procedure: Interval hypoxic-hyperoxic training (IHHT) using respiratory therapy unit ReOxy.; Procedure: Simulating Interval hypoxic-hyperoxic training (IHHT) using respiratory therapy unit ReOxy.

Detailed Description

The study will included 60 patients with metabolic syndrome (alimentary obesity (large waist, that measures at least 89 centimeters for women, and 102 centimeters for men), high blood pressure (130/85 mm Hg or higher), dislipidemia (triglyceride level 150 mg/dL (1.7 mmol/L) or higher of this type of fat found in blood; reduced high-density lipoprotein (HDL) cholesterol less than 40 mg/dL (1.04 mmol/L) in men, or less than 50 mg/dL (1.3 mmol/L) in women of HDL cholesterol), elevated fasting blood sugar (100 mg/dL (5,6 mmol/L) or higher). All patients were random separated into two groups: trial (30 pers., who will undergo 15 procedures of the IHHT, 5 days a week for 3 weeks), and control (30 pers., who will undergo 15 placebo procedures simulating IHHT, 5 days a week for 3 weeks). Before and after procedures of IHHT all patients will undergo laboratory and instrumental examinations, wich include arterial stiffness measurement, making by Fukuda Denshi VS-100 VaSera, measurement of liver tissue elasticity and fibrosis, making by elastography on FibroScan (Echosense, XL-sensor), and laboratory analysis (lipid profile, fasting blood sugar, trimethylamin N-oxyde (TMAO), Toll-like receptors 4,7,9). After 6 month of IHHT all patients will undergo the same laboratory and instrumental examinations to assess the duration of the effect.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119435
    • University Clinical Hospital №1 Sechenov University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient's written informed consent.
• The presence of metabolic syndrome: as having three or more of the following traits, including traits you're taking medication to control:
• Large waist - A waistline that measures at least 35 inches (89 centimeters) for women and 40 inches (102 centimeters) for men;
• High triglyceride level - 150 milligrams per deciliter (mg/dL), or 1.7 millimoles per liter (mmol/L), or higher of this type of fat found in blood;
• Reduced "good" or HDL cholesterol - Less than 40 mg/dL (1.04 mmol/L) in men or less than 50 mg/dL (1.3 mmol/L) in women of high-density lipoprotein (HDL) cholesterol;
• Increased blood pressure - 130/85 millimeters of mercury (mm Hg) or higher;
• Elevated fasting blood sugar - 100 mg/dL (5.6 mmol/L) or higher.
• Must be able to come to the hospital 5 days per week, for 3 weeks.

Exclusion Criteria:

• Refusal from further participation in the study.
• Individual intolerance to hypoxia.
• Cirrhosis of the liver with liver failure class C according to the classification of Child-Pugh.
• Alcohol use 140 g / week or more for men, and 70 g / week or more for women.
• Patients with positive serological reactions to hepatitis B and C.
• Chronic kidney disease (GFR less than 30 ml / min / 1.73 m 2).
• Pregnancy, lactation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group trial; Included 30 patients, with metabolic syndrome, aged 24-71 year old.	Procedure: Interval hypoxic-hyperoxic training (IHHT) using respiratory therapy unit ReOxy.; Every patient from control group undergo 15 procedures of IHHT, 5 procedures per week for 3 weeks, 1 procedure lasts 40 minutes. IHHT is a protocol which employs passive (the patient is at rest), short (several minutes) mild normobaric hypoxic exposures alternated with similar duration intervals of breathing hyperoxia, and repeated for 40 minutes. During the initial pretreatment test, the patient inhales air with low oxygen content at atmospheric pressure in a continuous mode through a mask. In the interval therapeutic mode that follows, periods of hypoxia (10-14% O2) are interrupted by periods of reoxygenation by hyperoxia (up to 35% O2). Automatic switching of gas flows (SRT technology). Built-in intelligent software automatically identifies and suggests key treatment parameters for the individual treatment program, by adjusting the starting parameters based upon the results of the pretreatment hypoxic test.
Experimental: Group control; Included 30 patients, with metabolic syndrome, aged 24-71 year old.	Procedure: Simulating Interval hypoxic-hyperoxic training (IHHT) using respiratory therapy unit ReOxy.; Every patient from group control undergo simulating procedures of interval hypoxic-hyperoxic training, 15 procedures, 5 procedures per week for 3 weeks. 1 procedure lasts 40 minutes, in normoxia. Before the start of the course, each patient undergoes a test procedure for 10 minute (in normoxia) for simulate procedures IHHT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the effect of interval hypoxy-hyperoxic training (IHHT) on the arterial stiffness.	Assessment of arterial stiffness will be measured by pulse wave velocity using VASERA VS-1500 Fukuda Denshi on next day after course of 15 procedures of IHHT.	Assessment will be measured next day after 15th procedure of the IHHT procedure.
Assess the effect of interval hypoxy-hyperoxic training (IHHT) on the liver fibrosis.	Assessment of the liver fibrosis and elasticity of liver tissue will be measurement by elastography on FibroScan (Echosense, XL-sensor) by measured liver tissue stiffness (in KPa).	Assessment will be measured next day after 15th procedure of the IHHT procedure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the effect of interval hypoxy-hyperoxic training (IHHT) on the lipid profile ( total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides in mmol/l).	Taken in blood.	Assessment will be measured next day after 15th procedure of the IHHT procedure.
Assess the effect of interval hypoxy-hyperoxic training (IHHT) on the trimethylamine n-oxide in mg/dl.	Taken in blood.	Assessment will be measured next day after 15th procedure of the IHHT procedure.

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2019
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): December 3, 2020

Study Registration Dates

• First Submitted: May 13, 2020
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 8, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Metabolic syndrome; Non-alcoholic Fatty Liver Disease; Vascular Aging; Non-drug methods; Interval Hypoxic-hyperoxic training; Trimethylamine N-oxyde (TMAO); Toll-like Receptors (TLR)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Liver Diseases; Insulin Resistance; Hyperinsulinism; Fibrosis; Syndrome; Metabolic Syndrome; Liver Cirrhosis
• Other Study ID Numbers: A0519

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Prohibition of local ethics committee

Drug and device information, study documents

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