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Rebreathing-induced Hypoxia and Glucose Levels

Primary Purpose

Hypoxemia

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Rebreathing-induced hypoxia
Spontaneous breathing
Sponsored by
University of Texas at Austin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoxemia

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Men and women aged 18 to 80 years old

Exclusion Criteria:

  • Have uncontrolled stage 2 hypertension (˃140/90 mmHg)
  • Are smokers
  • Are pregnant
  • Have a history of cardiovascular disease or indication of cardiovascular disease such as myocardial infarction, left ventricular hypertrophy, ischemic heart disease (or prior ischemia), stroke, and/or other vascular disease
  • Have a history of lung disease
  • Are taking insulin or more than one antihypertensive medication
  • Have poorly controlled diabetes: HbA1c levels ˃ 9%
  • Have been previously diagnosed with diabetic complications (nephropathy, neuropathy, retinopathy) by their family doctor

Sites / Locations

  • The Unviersity of Texas at AustinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Experimental

Arm Label

Spontaneous breathing

Rebreathing-induced hypoxia

Arm Description

Participants will be spontaneously breathing during an oral glucose tolerance test.

Participants will rebreathe room air from a low-volume closed-circuit system for a period of 2 minutes.

Outcomes

Primary Outcome Measures

Change in plasma glucose levels
Plasma glucose levels obtained from a venous catheter during a 2-hour oral glucose tolerance test

Secondary Outcome Measures

Full Information

First Posted
May 8, 2022
Last Updated
December 5, 2022
Sponsor
University of Texas at Austin
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1. Study Identification

Unique Protocol Identification Number
NCT05422430
Brief Title
Rebreathing-induced Hypoxia and Glucose Levels
Official Title
Effect of Rebreathing-induced Hypoxia on the Response to an Oral Glucose Tolerance Test
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 21, 2021 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas at Austin

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of this research project is to determine the effect of repeated maximal voluntary apneas on glucose uptake during an oral glucose tolerance test in healthy individuals, individuals with prediabetes and patients with type 2 diabetes.
Detailed Description
It is predicted that 1 in 3 adults will develop diabetes by 2050, implying that a large percentage of the population will become at high risk for cardiovascular disease, the most common cause of death in patients with type 2 diabetes. While regular exercise reduces insulin resistance and the elevated glucose levels associated with type 2 diabetes, only 28% of the adult population with diabetes meet physical activity recommendations. There is therefore an urgent need to identify alternative, non-pharmacological interventions that prevent and treat type 2 diabetes. A reduced oxygen availability, or hypoxia, is widely implicated in the development of insulin resistance. Paradoxically, hypoxia also triggers glucose uptake independently from the actions of insulin. Indeed, breathing low levels of oxygen stimulates glucose uptake in skeletal muscles by activating 5' adenosine monophosphate-activated protein kinase (AMPK). Discrepancies on the effect of hypoxia on glucose homeostasis may be attributed to the duration and type (nocturnal vs. diurnal) of hypoxic exposure. For example, the many severe hypoxic bouts associated with obstructive sleep apnea are associated with a worsened glycemic control while hypoxic exposure consisting of a limited number of short bouts of moderate hypoxia improves glycemic control. Therefore, an intervention that can induce brief hypoxic conditions, as observed through a reduced fraction of inspired oxygen, could attenuate the postprandial increase in glucose levels. Fraction of inspired oxygen can be reduced by rebreathing into a low-volume closed-circuit system containing ambient air for few minutes. Thus, the aim of this research project is to determine the effect of few bouts of rebreathing-induced hypoxia on glucose uptake during an oral glucose tolerance test in healthy individuals, individuals with prediabetes and patients with type 2 diabetes. If our expected outcomes are met, our next step will be to determine whether repeated sessions of rebreathing-induced hypoxia (5 sessions per week over 1-3 months) results in improvements in glycemic control.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Spontaneous breathing
Arm Type
Sham Comparator
Arm Description
Participants will be spontaneously breathing during an oral glucose tolerance test.
Arm Title
Rebreathing-induced hypoxia
Arm Type
Experimental
Arm Description
Participants will rebreathe room air from a low-volume closed-circuit system for a period of 2 minutes.
Intervention Type
Behavioral
Intervention Name(s)
Rebreathing-induced hypoxia
Intervention Description
Participants will rebreathe room air from a low-volume closed-circuit system for a period of 2 minutes.
Intervention Type
Behavioral
Intervention Name(s)
Spontaneous breathing
Intervention Description
Participants will be spontaneously breathing during an oral glucose tolerance test.
Primary Outcome Measure Information:
Title
Change in plasma glucose levels
Description
Plasma glucose levels obtained from a venous catheter during a 2-hour oral glucose tolerance test
Time Frame
Collected at min 0, 30, 60, 90 and 120 minutes of the oral glucose tolerance test

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Men and women aged 18 to 80 years old Exclusion Criteria: Have uncontrolled stage 2 hypertension (˃140/90 mmHg) Are smokers Are pregnant Have a history of cardiovascular disease or indication of cardiovascular disease such as myocardial infarction, left ventricular hypertrophy, ischemic heart disease (or prior ischemia), stroke, and/or other vascular disease Have a history of lung disease Are taking insulin or more than one antihypertensive medication Have poorly controlled diabetes: HbA1c levels ˃ 9% Have been previously diagnosed with diabetic complications (nephropathy, neuropathy, retinopathy) by their family doctor
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sophie Lalande
Phone
5122326485
Email
sophie.lalande@austin.utexas.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sophie Lalande
Organizational Affiliation
UT Austin
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Unviersity of Texas at Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78712
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chan Kean
Phone
512-471-6733
Email
ckean@austin.utexas.edu

12. IPD Sharing Statement

Citations:
PubMed Identifier
20969750
Citation
Boyle JP, Thompson TJ, Gregg EW, Barker LE, Williamson DF. Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. Popul Health Metr. 2010 Oct 22;8:29. doi: 10.1186/1478-7954-8-29.
Results Reference
background
PubMed Identifier
16505501
Citation
Resnick HE, Foster GL, Bardsley J, Ratner RE. Achievement of American Diabetes Association clinical practice recommendations among U.S. adults with diabetes, 1999-2002: the National Health and Nutrition Examination Survey. Diabetes Care. 2006 Mar;29(3):531-7. doi: 10.2337/diacare.29.03.06.dc05-1254.
Results Reference
background
PubMed Identifier
7789635
Citation
Azevedo JL Jr, Carey JO, Pories WJ, Morris PG, Dohm GL. Hypoxia stimulates glucose transport in insulin-resistant human skeletal muscle. Diabetes. 1995 Jun;44(6):695-8. doi: 10.2337/diab.44.6.695.
Results Reference
background
PubMed Identifier
2055841
Citation
Cartee GD, Douen AG, Ramlal T, Klip A, Holloszy JO. Stimulation of glucose transport in skeletal muscle by hypoxia. J Appl Physiol (1985). 1991 Apr;70(4):1593-600. doi: 10.1152/jappl.1991.70.4.1593.
Results Reference
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PubMed Identifier
11389854
Citation
Mu J, Brozinick JT Jr, Valladares O, Bucan M, Birnbaum MJ. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell. 2001 May;7(5):1085-94. doi: 10.1016/s1097-2765(01)00251-9.
Results Reference
background
PubMed Identifier
19265062
Citation
Louis M, Punjabi NM. Effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers. J Appl Physiol (1985). 2009 May;106(5):1538-44. doi: 10.1152/japplphysiol.91523.2008. Epub 2009 Mar 5.
Results Reference
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PubMed Identifier
28087818
Citation
Newhouse LP, Joyner MJ, Curry TB, Laurenti MC, Man CD, Cobelli C, Vella A, Limberg JK. Three hours of intermittent hypoxia increases circulating glucose levels in healthy adults. Physiol Rep. 2017 Jan;5(1):e13106. doi: 10.14814/phy2.13106. Epub 2017 Jan 13.
Results Reference
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PubMed Identifier
23536585
Citation
Duennwald T, Gatterer H, Groop PH, Burtscher M, Bernardi L. Effects of a single bout of interval hypoxia on cardiorespiratory control and blood glucose in patients with type 2 diabetes. Diabetes Care. 2013 Aug;36(8):2183-9. doi: 10.2337/dc12-2113. Epub 2013 Mar 27.
Results Reference
background
PubMed Identifier
28155101
Citation
Costalat G, Lemaitre F, Tobin B, Renshaw G. Intermittent hypoxia revisited: a promising non-pharmaceutical strategy to reduce cardio-metabolic risk factors? Sleep Breath. 2018 Mar;22(1):267-271. doi: 10.1007/s11325-017-1459-8. Epub 2017 Feb 2.
Results Reference
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PubMed Identifier
18097682
Citation
de Bruijn R, Richardson M, Schagatay E. Increased erythropoietin concentration after repeated apneas in humans. Eur J Appl Physiol. 2008 Mar;102(5):609-13. doi: 10.1007/s00421-007-0639-9. Epub 2007 Dec 19.
Results Reference
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Rebreathing-induced Hypoxia and Glucose Levels

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