High Altitude and Exogenous Carbohydrate Oxidation

• Sponsor: United States Army Research Institute of Environmental Medicine (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT03851744
• Collaborator: University of Arkansas (Other)
• Enrollment: 10
• Location: 1
• Arms: 2
• Actual Duration (Months): 21.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Recent studies have reported that oxidation of exogenous carbohydrate is reduced under acute hypobaric hypoxic (high altitude; HA) conditions compared to normoxia (sea level; SL) in native lowlanders. However, the mechanisms by which HA suppresses exogenous carbohydrate oxidation are not known. This study will seek to confirm that acute HA exposure decreases exogenous carbohydrate oxidation during steady-state aerobic exercise compared to SL, and explore if the mechanism inhibiting plasma glucose uptake is insulin dependent or independent.

Condition or Disease	Intervention/Treatment	Phase
Glucose Metabolism; High Altitude	Other: Sea Level; Other: High Altitude	N/A

Detailed Description

This randomized crossover study will examine substrate metabolic responses to ingesting supplemental carbohydrate during steady-state aerobic-type exercise at sea level (SL) and following acute (~5 h) exposure to HA (4,300 m) conditions in 10 healthy, recreationally active adults between the ages of 18-39 yrs. Following a 48-hr muscle glycogen normalization period, volunteers will complete 80-min of metabolically-matched, steady-state aerobic exercise on a treadmill, and consume 145 g of glucose (1.8 g·min-1) at SL and HA. Treadmill exercise will be performed at the same absolute workload, with speed and grade being the same at SL and HA to induce the same absolute workload between phases. SL and HA trials will occur in the US Army Research Institute of Environmental Medicine (USARIEM) hypobaric chamber and will be separated by a minimum 7-d washout period between each protocol day. 6-6-[2H2] glucose will be used as a tracer to assess glucose turnover. Indirect calorimetry, breath sampling for 13C/12C expired in CO2, and urine collections will be used to determine carbohydrate, fat, and protein oxidation during exercise at SL and HA. Serial blood draws will be collected during each trial to assess endocrine and circulating substrate responses to exercise, carbohydrate, and hypoxia. Muscle biopsies will be collected before and after steady-state exercise to examine intramuscular glucose transport expression and translocation, glycogen status, and activity enzyme intermediates in aerobic and anaerobic energy metabolism.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Mechanistic Effects of Acute Hypobaric Hypoxia on Exogenous Carbohydrate Utilization During Steady-state Aerobic Exercise
• Actual Study Start Date: Nov 28, 2018
• Actual Primary Completion Date: Nov 1, 2019
• Actual Study Completion Date: Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sea Level Carbohydrate metabolism measured at SL	Other: Sea Level; Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL
Experimental: High Altitude Carbohydrate metabolism measured at HA	Other: High Altitude; Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA

Outcome Measures

Primary Outcome Measures

1. Rate of Exogenous Carbohydrate Oxidation [7 hours]

   Use indirect calorimetry and stable isotope methodologies to measure if acute HA exposure changes the rate of exogenous carbohydrate oxidation during steady-state aerobic exercise compared to SL

2. Rate of Glucose Turnover [7 hours]

   Use stable isotope methodologies to measure if acute HA exposure changes the rate of glucose turnover during steady-state aerobic exercise compared to SL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 39 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Men aged 18 - 39 years

• Born at altitudes less than 2,100 m (~7,000 feet; Examples include Santa Fe, New Mexico; Laramie, Wyoming; Etc.)

• Physically active based on assessment of physical activity history (2-4 days per week aerobic and/or resistance exercise)

• Have supervisor approval (permanent party military and civilians)

• Willing to refrain from alcohol, smokeless nicotine products and dietary supplement use during study periods

• Refrain from taking any nonsteroidal anti-inflammatory drugs (NSAIDs; e.g. aspirin, Advil®, Aleve®, Naprosyn®, or any aspirin-containing product) for 10 days before and at least 5 days AFTER each muscle biopsy. (*Tylenol® or acetaminophen is ok to use if needed for discomfort)

Exclusion Criteria:

• Born at altitudes greater than 2,100 m (~7,000 feet; Examples include Santa Fe, New Mexico; Laramie, Wyoming; Etc.)

• Living in areas that are more than 1,200 m (~4,000 feet), or have traveled to areas that are more than 1,200 m for five days or more within the last 2 months (Examples include Ft. Huachuca, Arizona; Lima, Peru; Feldberg, Germany, Etc.)

• Musculoskeletal injuries that compromise exercise capability

• Metabolic or cardiovascular abnormalities (determined by resting ECG), gastrointestinal disorders (e.g., kidney disease, diabetes, cardiovascular disease, etc.)

• Medication that affects macronutrient metabolism (i.e., diabetes medications, statins, corticosteroids, etc) and/or the ability to participate in strenuous exercise

• Evidence of apnea or other sleeping disorders

• Prior diagnosis of high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE)

• Presence of asthma or respiratory tract infections (< 1 month prior)

• Allergies or intolerance to foods (including but not limited to lactose intolerance/milk allergy), vegetarian practices, or medications (including, but not limited to, lidocaine ) to be utilized in the study

• Smoking or vaping

• History of complications with lidocaine

• Taking medications that interfere with oxygen delivery and transport (Includes sedatives, sleeping aids, tranquilizers and/or any medication that depresses ventilation, diuretics, alpha and beta blockers)

• Evidence of any physical, mental, and/or medical conditions that would make the proposed studies relatively more hazardous as determined by the Office of Medical Support and Oversight

• Present condition of alcoholism, anabolic steroids, or other substance abuse issues

• Anemia (hematocrit <38% and hemoglobin <12.5 g/dL) and Sickle Cell Anemia/Trait

• Abnormal prothrombin time (PT)/ partial thromboplastin time (PTT) test or problems with blood clotting

• Blood donation within 8 weeks of beginning the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USARIEM	Natick	Massachusetts	United States	01760

Sponsors and Collaborators

• United States Army Research Institute of Environmental Medicine
• University of Arkansas

Investigators

• Principal Investigator: Lee M Margolis, PhD, Military Nutrition Division, USARIEM

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 11, 2019

More Information

Publications

None provided.

• Responsible Party: United States Army Research Institute of Environmental Medicine
• ClinicalTrials.gov Identifier: NCT03851744
• Other Study ID Numbers: 18-09HC
• First Posted: Feb 22, 2019
• Last Update Posted: Sep 2, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Altitude Sickness

Study Results

Participant Flow

Pre-assignment Detail	No significant events happen prior to assignment of participants to a study arm.

Arm/Group Title	Sea Level First, Then High Altitude	High Altitude First, Then Sea Level
Arm/Group Description	Carbohydrate metabolism measured at SL first then HA Sea Level: Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL 7 day washout High Altitude: Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA	Carbohydrate metabolism measured at HA first then SL High Altitude: Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA 7 day washout Sea Level: Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL
Period Title: Overall Study
STARTED	4	6
COMPLETED	4	4
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Sea Level First, Then High Altitude	High Altitude, Then Sea Level	Total
Arm/Group Description	Carbohydrate metabolism measured at SL, then HA Sea Level: Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL 7 day washout High Altitude: Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA	Carbohydrate metabolism measured at HA, then SL High Altitude: Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA 7 day washout Sea Level: Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL	Total of all reporting groups
Overall Participants	4	6	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	6 100%	10 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	4 100%	6 100%	10 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	4 100%	6 100%	10 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	6 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Rate of Exogenous Carbohydrate Oxidation
Description	Use indirect calorimetry and stable isotope methodologies to measure if acute HA exposure changes the rate of exogenous carbohydrate oxidation during steady-state aerobic exercise compared to SL
Time Frame	7 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sea Level	High Altitude
Arm/Group Description	Carbohydrate metabolism measured at SL Sea Level: Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL	Carbohydrate metabolism measured at HA High Altitude: Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA
Measure Participants	8	8
Mean (Standard Deviation) [g/min]	0.44 (0.05)	0.35 (0.07)

2. Primary Outcome

Title	Rate of Glucose Turnover
Description	Use stable isotope methodologies to measure if acute HA exposure changes the rate of glucose turnover during steady-state aerobic exercise compared to SL
Time Frame	7 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sea Level	High Altitude
Arm/Group Description	Carbohydrate metabolism measured at SL Sea Level: Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL	Carbohydrate metabolism measured at HA High Altitude: Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA
Measure Participants	8	8
Glucose Rate of Disappearance	14.3 (2.0)	12.7 (1.7)
Metabolic Clearance Rate	12.1 (2.3)	8.9 (1.8)

Adverse Events

Time Frame	3 weeks
Arm/Group Title	Sea Level		High Altitude
Arm/Group Description	Carbohydrate metabolism measured at SL Sea Level: Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL		Carbohydrate metabolism measured at HA High Altitude: Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA
All Cause Mortality
	Sea Level		High Altitude
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)
Serious Adverse Events
	Sea Level		High Altitude
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Sea Level		High Altitude
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.