Insulin Sensitivity During Hyperbaric Oxygen Compared to Hyperbaric Air

NCT ID: NCT03138746

Last Updated: 2020-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

25 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-08-13

Study Completion Date

2020-01-15

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Diabetes Mellitus, Type II Insulin Resistance

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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HBO

On day 2, the participant will undergo a 2-hour hyperbaric exposure breathing 100% oxygen

HBO

Intervention Type PROCEDURE

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

Hyperbaric air

Intervention Type PROCEDURE

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

Interventions

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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

Intervention Type 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

Intervention Type PROCEDURE

Eligibility Criteria

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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)
Minimum Eligible Age

40 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Royal Adelaide Hospital

OTHER

Sponsor Role collaborator

University of Adelaide

OTHER

Sponsor Role lead

Responsible Party

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A/Prof Leonie Heilbronn

ARC Future Fellow

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David C Wilkinson, FANZCA

Role: PRINCIPAL_INVESTIGATOR

University of Adelaide

Locations

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Hyperbaric Medicine Unit, Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Countries

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Australia

References

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Wilkinson D, Chapman IM, Heilbronn LK. Hyperbaric oxygen therapy improves peripheral insulin sensitivity in humans. Diabet Med. 2012 Aug;29(8):986-9. doi: 10.1111/j.1464-5491.2012.03587.x.

Reference Type BACKGROUND
PMID: 22269009 (View on PubMed)

Wilkinson D, Nolting M, Mahadi MK, Chapman I, Heilbronn L. Hyperbaric oxygen therapy increases insulin sensitivity in overweight men with and without type 2 diabetes. Diving Hyperb Med. 2015 Mar;45(1):30-6.

Reference Type BACKGROUND
PMID: 25964036 (View on PubMed)

Other Identifiers

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R20160801

Identifier Type: -

Identifier Source: org_study_id