Acute Hyperbaric Oxygen Treatment Increases Hepatic Insulin Sensitivity and Muscle Reactive Oxygen Species in T2D

NCT ID: NCT04219215

Last Updated: 2023-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2022-09-20

Brief Summary

Diabetes mellitus type 2 (T2D) is characterized by insulin resistance of liver and skeletal muscle, which is at least partly due to impaired muscle mitochondrial function. Long-term HBO therapy, as applied for treating the diabetic foot syndrome, has been shown to improve blood glucose concentrations. To study the underlying mechanisms, we want to examin the short-term effect of HBO treatment on insulin sensitivity and mitochondrial oxidative capacity and production of reactive oxygen species (ROS) in a randomized, double blinded, placebo-controlled cross-over trial.

Detailed Description

In total 14 patients are planned. Each participant participates in both experimental parts (100% O2 and ambient air). They are examined immediately after each HBO/ ambient air therapy. The allocation is randomized treated every three weeks with 2-hour therapies using pure O2 or indoor air. Randomized and double-blinded in a cross-over setting, one group of patients with type 2 diabetes is first treated with HBO therapy and the other group is first treated with room air. Here, an ambient pressure of 2.4 ATM is built up and then administered for respiration over a total of 90 minutes of pure O2. Patients are examined on two consecutive days for each part of the study.On the first day serum samples are taken and a sample is taken from the vastus lateralis muscle. A magnetic resonance spectroscopic examination (MRS) is performed on the patient subsequently. In this case, phosphorus metabolites (absolute quantification of ATP, Pi) and the ATP synthase flow rate (fATP) are determined non-invasively by means of 31P MRS and TG storage (HCL) by means of 1H-MRS.

On the next day of the trial patients are treated with HBO therapy or room air. A hyperinsulinemic-euglycemic clamp test (120-300 min) with administration of deuterated glucose (D- [6,6-2H2] glucose) (0-120 min) to measure muscular and hepatic insulin resistance will be performed after the end of HBO therapy or room air treatment performed. Indirect calorimetry determines energy consumption and substrate selection (lipid and glucose oxidation) in hyperinsulinaemia. After the end of the HBO therapy or room air treatment and 30 minutes after the start of the clamp test, a sample is taken from the vastus lateralis muscle again.

Conditions

Type 2-diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Hyperbaric oxygenation

Patients with T2D receive an 2 hour treatment with 100 % oxygen in a hyperbaric chamber

Group Type: EXPERIMENTAL

100% O2 in oxygen chamber

Intervention Type: DEVICE

Application of 100% O2 in an hyperbaric oxygen chamber

21% O2 in oxygen chamber

Intervention Type: DEVICE

Application of ambient air (21% O2) in an hyperbaric oxygen chamber

Ambient Air

Patients with T2D receive an 2 hour treatment with 21% oxygen in a hyperbaric chamber

Group Type: EXPERIMENTAL

100% O2 in oxygen chamber

Intervention Type: DEVICE

Application of 100% O2 in an hyperbaric oxygen chamber

21% O2 in oxygen chamber

Intervention Type: DEVICE

Application of ambient air (21% O2) in an hyperbaric oxygen chamber

Interventions

100% O2 in oxygen chamber

Application of 100% O2 in an hyperbaric oxygen chamber

Intervention Type: DEVICE

21% O2 in oxygen chamber

Application of ambient air (21% O2) in an hyperbaric oxygen chamber

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 and ≤ 75 years
• Type 2 diabetes
• HbA1c ≥ 6 and ≤ 9%
• BMI ≤ 35 kg / m2

Exclusion Criteria

• Treatment with thiazolidinedione in the last 6 months
• Uncontrolled hyperglycemia (FPG ≥ 240 mg / dl)
• vitamin supplement (washing out at least 4 weeks)
• Patients requiring revascularization
• Serum CRP ≥ 5 mg / dl
• Previous treatment for HBO therapy
• Secondary diabets according to ADA criteria (type 3 B-H, eg pancreopriver diabetes)
• Type 4 diabetes (gestational diabetes), pregnancy
• poor glycemic control (HbA1c> 9.0%)
• Hyperlipidemia (low density triglycerides and lipoproteins ≥ double upper Reference limit)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

German Diabetes Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Roden, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

German Diabetes Center

Locations

German Diabetes Center

Düsseldorf, North Rhine-Westphalia, Germany

Countries

Germany

References

Sarabhai T, Mastrototaro L, Kahl S, Bonhof GJ, Jonuscheit M, Bobrov P, Katsuyama H, Guthoff R, Wolkersdorfer M, Herder C, Meuth SG, Dreyer S, Roden M. Hyperbaric oxygen rapidly improves tissue-specific insulin sensitivity and mitochondrial capacity in humans with type 2 diabetes: a randomised placebo-controlled crossover trial. Diabetologia. 2023 Jan;66(1):57-69. doi: 10.1007/s00125-022-05797-0. Epub 2022 Sep 30.

Reference Type: DERIVED

PMID: 36178534 (View on PubMed)

Other Identifiers

HBO

Identifier Type: -

Identifier Source: org_study_id