Clinical trial NCT05147116: The Effect of Hypoxia on Type 2 Diabetes and Weight Loss
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type2 Diabetes
Lead sponsor: University of Portsmouth
Sponsor class: OTHER
Collaborators: name: Bournemouth University
name: University College, London
name: University of Cambridge
name: Portsmouth Hospitals NHS Trust
First posted: 2021-12-07
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single blind, randomized, balanced, crossover design study
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Δ Mean AUC (Area Under the Curve) Plasma [Glucose]
timeFrame: 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.
Secondary outcomes:
measure: Δ Body Mass
timeFrame: 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.
measure: Δ Total Minutes of Physical Activity (Light, Moderate, Moderate to Vigorous Physical Activity).
timeFrame: 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.
measure: Δ Sleep Efficiency (Percentage of Time Spent Asleep While in Bed)
timeFrame: 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.
measure: Δ IL-6
timeFrame: 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.
measure: Δ TNFɑ
timeFrame: 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.
Other outcomes:
Locations:
city: Portsmouth
country: United Kingdom
facility: Anthony Shepherd
state: Hampshire
Study officials:
affiliation: University of Portsmouth
name: Anthony Shepherd, PhD
role: PRINCIPAL_INVESTIGATOR
References: