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Insulin Sensitivity During Hyperbaric Oxygen Compared to Hyperbaric Air (HOTAIR4)

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ClinicalTrials.gov Identifier: NCT03138746
Recruitment Status : Recruiting
First Posted : May 3, 2017
Last Update Posted : September 5, 2018
Sponsor:
Collaborator:
Royal Adelaide Hospital
Information provided by (Responsible Party):
A/Prof Leonie Heilbronn, University of Adelaide

Brief Summary:

In a recent series of studies performed by our group, we have shown that exposure to hyperbaric oxygen (HBO) leads to an increase in insulin sensitivity in male subjects with type-2 diabetes (T2DM) and in obese and overweight men without diabetes. The aim of this study is to investigate the relationship between pressure and oxygen in producing this effect, specifically, is this effect measurable in hyperbaric air or is some higher pressure of oxygen required?

Aims:

  1. To determine whether the insulin sensitising effect of HBO is apparent in hyperbaric air at the same pressure as HBO.
  2. To examine mechanisms underpinning the increase in insulin sensitivity following HBO.

Condition or disease Intervention/treatment
Diabetes Mellitus, Type II Insulin Resistance Procedure: HBO Procedure: Hyperbaric air

Detailed Description:

The 40 participants will be randomly allocated to two groups, matched for BMI. All participants will attend the Hyperbaric Medicine Unit on 2 occasions and metabolic testing will be undertaken at the same time of the day. Day 1 will be for baseline assessment sitting outside the hyperbaric chamber. Day 2 will be two days after Day 1 in the same week during which participants will undergo a 2-hour session in the hyperbaric chamber with a "10:90:30" compression profile (compression of the chamber in air to 2 atmospheres absolute, then donning a "hood" supplying high flow gas for 90-minutes followed by a linear decompression back to 1 atmosphere absolute over 30-minutes). Half of the participants will breathe oxygen during this compression profile while the other half will breathe medical air.

An overnight fast (10-hours) will be required prior to each day with modification of their diabetic medication. This regimen will be monitored in consultation with a diabetes specialist (IC):

  • If prescribed metformin, withhold the evening dose before each study day but give other usual evening oral drugs
  • If taking evening insulin, reduce dose to 2/3 of usual dose the night before each study day
  • Hold diabetes drugs (oral or injectable) on morning of study until conclusion of study and then administer with food. Take usual morning oral medication at this time and modified insulin dose (if prescribed insulin)
  • Check BSL on arrival and departure each study day

Day 1. Baseline assessment. The participant will attend at 0900 for a hyperinsulinaemic euglycaemic clamp, which will be performed with the same protocol as used in our three previous clamp studies. Two intravenous cannulae are inserted into veins in contralateral forearms using local anaesthetic (lignocaine 1%). Baseline blood is taken for fasting glucose and insulin and a primed insulin infusion is started (80mU/m2/min) for 3½ hours. Blood samples (<2mls) are obtained at 5-10 minute intervals so that blood glucose can be maintained at 5.5 mmol/L with a variable infusion of 25% Dextrose and a trained individual will be present for the duration of the clamping procedure. Insulin sensitivity will be assessed by the steady state glucose infusion rate calculated over a stable 30-minute period of the clamp. Assessments will be made at two points during the 3½ hour clamp; at 2½-3 hours and 3-3½ hours. Immediately post-clamp, volunteers are given orange juice and high carbohydrate lunch, and the glucose infusion is maintained on halving scale for 5 minutes each for at least 20 minutes. Blood sugar levels are monitored every 10-15 minutes for 60 minutes. Total blood taken during the clamping procedure will be less than 100mls including baseline samples. The researchers have performed several hundred clamps.

Day 2. The participant will attend at 0900 for a second 3½-hour hyperinsulinaemic euglycaemic clamp, similar to Day1. The procedure for the two groups (HBO and hyperbaric air) will be identical, the only difference will be the breathing gas used during the 10:90:30 hyperbaric exposures. The breathing gas delivered to the participant (oxygen or air) will be supplied from masked "research" gas outlets, so the participant will be blinded as to which group they are in. The participant will enter the chamber after a 1-hour clamp stabilising period and assessment of the steady state glucose infusion rate will take place at similar times to Day1. This means that during the 2-hour hyperbaric exposure, the assessment periods will correspond to the 30-minute decompression at the end of the hyperbaric session and the first 30-minutes after exit from the hyperbaric chamber. Post clamp will be managed as during Day1.

Blood samples (20 ml) for inflammatory markers will be taken before and after procedures on both days. With blood taken during 2 clamps (less than 100mls each) and four 20 ml samples, total blood taken will be approximately 280 ml.


Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Insulin Sensitivity During Hyperbaric Oxygen Compared to Hyperbaric Air
Actual Study Start Date : August 13, 2018
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Insulin

Group/Cohort Intervention/treatment
HBO
On day 2, the participant will undergo a 2-hour hyperbaric exposure breathing 100% oxygen
Procedure: HBO
Compression in a hyperbaric chamber in air to 2 atmospheres absolute, then donning a "hood" supplying high flow oxygen for 90-minutes followed by a linear decompression back to 1 atmosphere over 30 minutes

Hyperbaric air
On day 2, the participant will undergo a 2-hour hyperbaric exposure breathing air
Procedure: Hyperbaric air
Compression in a hyperbaric chamber in air to 2 atmospheres absolute, then donning a "hood" supplying high flow air for 90-minutes followed by a linear decompression back to 1 atmosphere over 30 minutes




Primary Outcome Measures :
  1. insulin sensitivity [ Time Frame: Baseline to Day 2 ]
    As measured by the glucose infusion rate during the steady-state phase of the hyperinsulinaemic euglycaemic clamp on day 2


Secondary Outcome Measures :
  1. change in inflammatory cytokines [ Time Frame: Day 1 and 2 ]
    analysis of serum inflammatory markers pre and post procedures on Days 1 and 2


Biospecimen Retention:   Samples Without DNA
Serum


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Community sample
Criteria

Inclusion Criteria:

  • Men with T2DM, n=40 (numbers are based on power analysis of previous studies)
  • Normal to obese weight (BMI 25-40 kg/m2)
  • Age > 40 (no specific upper age limit)
  • All participants will attend the Hyperbaric Medicine Unit to be assessed by a hyperbaric physician (DW) to determine fitness to enter the hyperbaric chamber the standard clinical criteria of the Hyperbaric Medicine Unit will be used

Exclusion Criteria:

  • use of prescribed or non-prescribed medications which may affect glucose homeostasis (eg steroids)
  • uncontrolled asthma, current fever, upper respiratory infections
  • individuals who regularly perform high intensity exercise (>2 week)
  • current intake of > 140g alcohol/week
  • current smokers of cigarettes/cigars/marijuana
  • current intake of any illicit substance
  • experience claustrophobia in confined spaces
  • has donated blood within past 3-months
  • has been involved in any other study within the past 3-months
  • unable to comprehend study protocol
  • any other contraindication to HBO (eg Eustachian tube dysfunction making middle ear inflation ineffective)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03138746


Contacts
Contact: David C Wilkinson, FANZCA +61 8 7074 0180 david.wilkinson@sa.gov.au
Contact: Leonie K Heilbronn, PhD +61 8 8128 4838 leonie.heilbronn@adelaide.edu.au

Locations
Australia, South Australia
Hyperbaric Medicine Unit, Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Contact: David C Wilkinson, FANZCA    61 8 7074 0180    david.wilkinson@sa.gov.au   
Principal Investigator: David C Wilkinson, FANZCA         
Sub-Investigator: Ian M Chapman, PhD         
Sub-Investigator: Leonie K Heilbronn, PhD         
Sponsors and Collaborators
University of Adelaide
Royal Adelaide Hospital
Investigators
Principal Investigator: David C Wilkinson, FANZCA University of Adelaide

Publications:
Responsible Party: A/Prof Leonie Heilbronn, ARC Future Fellow, University of Adelaide
ClinicalTrials.gov Identifier: NCT03138746     History of Changes
Other Study ID Numbers: R20160801
First Posted: May 3, 2017    Key Record Dates
Last Update Posted: September 5, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by A/Prof Leonie Heilbronn, University of Adelaide:
hyperbaric oxygenation
insulin sensitivity
human
inflammation

Additional relevant MeSH terms:
Insulin Resistance
Diabetes Mellitus
Hypersensitivity
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Immune System Diseases
Hyperinsulinism
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs