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Completed

NCT Number: NCT05147116

The Effect of Hypoxia on Type 2 Diabetes and Weight Loss

The number of people with type 2 diabetes mellitus (T2DM) continuing to rise, this pandemic is expected to reach 700 million people by 2045. T2DM is a metabolic condition characterized by progressive insulin resistance and chronic hyperglycemia (high blood glucose concentrations). Hyperglycaemia increases the risk of both micro- and macrovascular damage, whilst interventions that reduce blood glucose mitigate this risk. Weight loss, achieved through exercise and dietary modification, is effective at reducing hyperglycaemia. However, despite the clear benefits of exercise and weight loss, diverse psychological, sociological and logistical factors can make it difficult for some individuals with T2DM to initiate, or adhere to, these lifestyle interventions. Alternative approaches to treatment are therefore required.

The purpose of this research project is to investigate whether 10-days of overnight exposure to moderate hypoxia is effective at improving blood glucose control in individuals with T2DM and to provide insight into the physiological mechanisms responsible for any beneficial effects.

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Key information

Conditions

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Anthony Shepherd

Portsmouth, Hampshire, PO1 2ER, United Kingdom

About this study

Type 2 diabetes mellitus (T2DM) is a metabolic condition characterized by progressive insulin resistance and chronic hyperglycemia (high blood glucose concentrations). Hyperglycaemia increases the risk of both micro- and macrovascular damage, whilst interventions that reduce blood glucose mitigate this risk. Weight loss, achieved through exercise and dietary modification, is effective at reducing hyperglycaemia. However, despite the clear benefits of exercise and weight loss, diverse psychological, sociological and logistical factors can make it difficult for some individuals with T2DM to initiate, or adhere to, these lifestyle interventions. With the number of people with T2DM continuing to rise, this pandemic is expected to reach 700 million people by 2045. Thus, there is a clear need for cost-effective interventions that can effectively improve glycaemic control in people with T2DM and which people will adhere to.

A simple exposure to a lowered concentration of inspired oxygen (i.e. hypoxia) may represent such an intervention. In addition to the beneficial effects on glucose homeostasis that have been reported following a single acute hypoxic exposure, repeated intermittent, or continuous, hypoxic exposure may also have therapeutic potential in individuals with T2DM. In rodent models, daily hypoxic exposures returned fasting blood [glucose] to normal levels and increased glucose transporter 4 translocation in mice with T2DM. Similar effects on glucose homeostasis have been shown in overweight humans and those with insulin resistance, (during intermittent hypoxic training) which was explained, at least in part, by reduction in body mass (~ 1.2 kg).

The mechanisms underpinning the improved glycaemic control in response to hypoxia are likely multifactorial. Specifically, our objective is to assess a novel therapeutic intervention for the treatment and management of T2DM which overcomes many of the barriers to uptake and adherence that are associated with some lifestyle interventions such as exercise and weight loss.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Males and post-menopausal women with T2DM (as diagnosed with the WHO criteria).

Exclusion criteria

  • Individuals with contraindications to hypoxic exposure (e.g. obstructive sleep apnoea, extant cardiac conditions or on medications such as SGLT2 inhibitors or PPAR antagonists).

Treatment and study plan

Sleeping in a tent

Other

Participants will spend 10 consecutive nights of sleeping in a tent

Primary outcomes

  1. Δ Mean AUC (Area Under the Curve) Plasma [Glucose]

    Time frame: Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.

    Does 10 days of overnight hypoxia change AUC during a oral glucose tolerance test. Units for AUC are AU (arbitrary units) which have been derived from the trapezoidal method and have been published as such. Trapezoidal method: AUC = Δx ((y0/2)+y1+y2+y3+...+(yn/2)).

    Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.

Secondary outcomes

  1. Δ Body Mass

    Time frame: Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.

    Does 10 days of overnight hypoxia change body mass - assessed via DXA.

    Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.

  2. Δ Total Minutes of Physical Activity (Light, Moderate, Moderate to Vigorous Physical Activity).

    Time frame: Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.

    Does 10 days of overnight hypoxia change physical activity - assessed via wrist worn accelerometry.

    Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.

  3. Δ Sleep Efficiency (Percentage of Time Spent Asleep While in Bed)

    Time frame: Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.

    Does 10 days of overnight hypoxia change sleep - assessed via wrist worn accelerometry.

    Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.

  4. Δ IL-6

    Time frame: Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.

    Does 10 days of overnight hypoxia change IL-6.

    Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.

  5. Δ TNFɑ

    Time frame: Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.

    Does 10 days of overnight hypoxia change TNFɑ.

    Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.

Sponsors and collaborators

Lead sponsor

University of Portsmouth

Other

Collaborators

  • Bournemouth University
  • Portsmouth Hospitals NHS Trust
  • University College, London
  • University of Cambridge

Registry information

Official study title

The Effects of Repeated Moderate Overnight Normobaric Hypoxia on Glucose Homeostasis, Appetite, Body Weight, Inflammation and Oxidative Stress in Individuals With Type 2 Diabetes Mellitus

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Dec 7, 2021
Registry last updated
Jan 24, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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