High AltitudePhase 4NCT06164665
Effects of Pioglitazone on Exogenous Carbohydrate Oxidation During Steady-State Exercise at High Altitude
A Phase 4 study testing Pioglitazone 15mg in people with High Altitude, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
Trial summary
Apparent hypoxia-induced insulin insensitivity along with alterations in glucose kinetics suggests reduction in glucose uptake by the peripheral tissue is a primary factor contributing to reductions in exogenous glucose oxidation at HA. Read more about this study
- Who is it for?
- Ages 18 to 39 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- High Altitude
- What is being tested?
- Pioglitazone 15mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2023to 1 Jul 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men aged 18 - 39 years
- Born at altitudes less than 2,100 m
- Physically active (exercise minimum 2 days per week)
- Have supervisor approval (permanent party military and civilians)
- Willing to refrain from alcohol, smokeless nicotine products and dietary supplement use during study periods
- Fully vaccinated against COVID-19
Who cannot join
- Born at altitudes greater than 2,100 m
- Musculoskeletal injuries that compromise exercise capability
- Metabolic or cardiovascular abnormalities, or gastrointestinal disorders
- Taking medication that affects macronutrient metabolism and/or the ability to participate in strenuous exercise
- Living in areas that are more than 1,200 m, or traveled to areas that are more than 1,200 m for five days or more within 2 months of data collection
- Evidence of apnea or other sleeping disorders
Show all 14Show fewer
- Prior diagnosis of high altitude pulmonary edema or high altitude cerebral edema
- Presence of asthma or respiratory tract infections
- Smoking or vaping
- Taking medications that interfere with oxygen delivery and transport
- Anemia (HCT <38% and HBG <12.5 g/dL) and Sickle Cell Anemia/Trait
- Blood donation within 8 weeks of beginning the study
- Unwilling or unable to consume study diets or foods provided due to personal preference, dietary restrictions, and/or food allergies
- Unwilling or unable to adhere to study physical restrictions
Trial locations and contacts
1 site in 1 country.
United States1 site
US Army Research Institute of Environmental Medicine
Natick, Massachusetts, 01760
About this study
Apparent hypoxia-induced insulin insensitivity along with alterations in glucose kinetics suggests reduction in glucose uptake by the peripheral tissue is a primary factor contributing to reductions in exogenous glucose oxidation at HA. As such, the primary objective of this study is to determine the ability of an insulin sensitizer (Pioglitazone, PIO) to enhance exogenous glucose oxidation and metabolic clearance rate during metabolically-matched, steady-state exercise during acute HA exposure compared to placebo (PLA) in native lowlanders. Secondary objective of this study will be to assess the impact of PIO on markers of inflammation and iron status compared to PLA. This randomized crossover placebo control double blinded study will examine substrate oxidation and glucose kinetic responses to ingesting supplemental carbohydrate (glucose) during metabolically-matched, steady-state exercise with acute (~5 h) exposure to HA (460 mmHg, or 4300m, barometric pressure similar to Pike's Peak) after receiving PIO (HA+PIO), or after receiving a matched placebo (HA+PLA). Eight healthy, recreationally active males between the ages of 18-39 yrs will be required to complete this study. Following a 4 day glycogen normalization period receiving PIO or PLA daily, volunteers will complete two 80-min trials, performing metabolically-matched, steady-state aerobic (same absolute workload corresponding to ~55 ± 5% of V̇O2peak at HA) exercise on a treadmill, and consuming 145 g of glucose (1.8 g/min); one trial with HA+PIO and the other with HA+PLA. A dual glucose tracer (13C-glucose oral ingestion and [6,6-2H2]-glucose primed, continuous infusion) technique and indirect calorimetry will be used to selectively analyze endogenous and exogenous glucose oxidation, as well as glucose rate of appearance (Ra), disappearance (Rd) and metabolic clearance rate (MCR). Serial blood samples will be collected during each trial to assess endocrine and circulating substrate responses to exercise, carbohydrate, and hypoxia with or without PIO. All trials will occur at the same time of day in the USARIEM hypobaric/hypoxic chamber and be separated by a minimum 10-d washout period. The primary risks associated with this study include those associated with acute hypobaric hypoxia, exercise, and blood sampling.
Read the detailed description
This randomized crossover placebo controlled double blinded study will examine substrate oxidation and glucose kinetic responses to ingesting supplemental carbohydrate (glucose) during metabolically-matched, steady-state exercise with acute (~5 h) exposure to HA (460 mmHg) after short-term (5 days) use of Pioglitazone (HA+PIO), or matched placebo (HA+PLA). Eight healthy, recreationally active males between the ages of 18-39 yrs will be enrolled. Following a 48-hr muscle glycogen normalization period, volunteers will complete 80-min of metabolically-matched, steady-state (same absolute workload corresponding to ~55 ± 5% of V̇O2peak at HA) exercise on a treadmill, and consume 145 g of glucose (1.8 g/min) with HA+PIO and HA+PLA. A dual glucose tracer (13C-glucose oral ingestion and [6,6-2H2]-glucose primed, continuous infusion) technique and indirect calorimetry will be used to analyze endogenous and exogenous glucose oxidation, as well as glucose rate of appearance (Ra), disappearance (Rd), and MCR. Serial blood samples will be collected during each trial to assess endocrine and circulating substrate responses to exercise, carbohydrate, and hypoxia, with or without PIO. Isotope methodology and aerobic exercise protocols will be identical to our previous work (3, 4), allowing comparison of outcomes across studies. All trials will be conducted in the USARIEM hypobaric/hypoxic chamber and be separated by a minimum 10-d washout period.
- Conditions
- High Altitude
- Being tested
- Pioglitazone 15mg, Placebo
- Medical subject headings
- Altitude Sickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pioglitazone 15mgDrug
Also called Actos
Pioglitazone (PIO) will be administered as a 15 mg oral dose per day for 5 days
PlaceboOther
100% microcrystalline cellulos
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Experimental | Pioglitazone administered as a 15 mg oral dose per day for 5 days Receives: Drug: Pioglitazone 15mg |
| Placebo | Experimental | Microcrystalline cellulose pill administered as an oral dose per day for 5 days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Exogenous Glucose Oxidation
Determine the effects of PIO on exogenous glucose oxidation (g/min) during exercise under acute HA exposure compared to PLA
Measured: 8 hours
Secondary outcomes (2)
Concentration of Interleukin-6
Determine the effects of PIO on inflammation during acute HA exposure compared to PLA.
Measured: 8 hours
Concentration of Serum Hemoglobin
Determine the effects of PIO on markers of iron status during acute HA exposure compared to PLA
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2023
- Study start1 Mar 2023
- Primary completion1 Jul 2023
- Study completion1 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for High AltitudeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- randomized crossover placebo controlled double blinded study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- United States Army Research Institute of Environmental Medicine
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06164665
- Sponsor's protocol ID
- 22-07H
- Status last verified
- May 2025
- First submitted
- 19 Sep 2023
- Last updated
- 19 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Pioglitazone on Exogenous Carbohydrate Oxidation During Steady-State Exercise at High Altitude
- ClinicalTrials.gov ID
- NCT06164665
- Acronym / sponsor ID
- 22-07H
- Conditions
- High Altitude
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- United States Army Research Institute of Environmental MedicineUS federal agency
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 1 Jul 2023 (actual)
- Study completion
- 1 Jul 2023 (actual)
- First posted
- 11 Dec 2023 (actual)
- Results
- Posted 19 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Apparent hypoxia-induced insulin insensitivity along with alterations in glucose kinetics suggests reduction in glucose uptake by the peripheral tissue is a primary factor contributing to reductions in exogenous glucose oxidation at HA. As such, the primary objective of this study is to determine the ability of an insulin sensitizer (Pioglitazone, PIO) to enhance exogenous glucose oxidation and metabolic clearance rate during metabolically-matched, steady-state exercise during acute HA exposure compared to placebo (PLA) in native lowlanders. Secondary objective of this study will be to assess the impact of PIO on markers of inflammation and iron status compared to PLA. This randomized crossover placebo control double blinded study will examine substrate oxidation and glucose kinetic responses to ingesting supplemental carbohydrate (glucose) during metabolically-matched, steady-state exercise with acute (~5 h) exposure to HA (460 mmHg, or 4300m, barometric pressure similar to Pike's Peak) after receiving PIO (HA+PIO), or after receiving a matched placebo (HA+PLA). Eight healthy, recreationally active males between the ages of 18-39 yrs will be required to complete this study. Following a 4 day glycogen normalization period receiving PIO or PLA daily, volunteers will complete two 80-min trials, performing metabolically-matched, steady-state aerobic (same absolute workload corresponding to ~55 ± 5% of V̇O2peak at HA) exercise on a treadmill, and consuming 145 g of glucose (1.8 g/min); one trial with HA+PIO and the other with HA+PLA. A dual glucose tracer (13C-glucose oral ingestion and [6,6-2H2]-glucose primed, continuous infusion) technique and indirect calorimetry will be used to selectively analyze endogenous and exogenous glucose oxidation, as well as glucose rate of appearance (Ra), disappearance (Rd) and metabolic clearance rate (MCR). Serial blood samples will be collected during each trial to assess endocrine and circulating substrate responses to exercise, carbohydrate, and hypoxia with or without PIO. All trials will occur at the same time of day in the USARIEM hypobaric/hypoxic chamber and be separated by a minimum 10-d washout period. The primary risks associated with this study include those associated with acute hypobaric hypoxia, exercise, and blood sampling.
Detailed description
This randomized crossover placebo controlled double blinded study will examine substrate oxidation and glucose kinetic responses to ingesting supplemental carbohydrate (glucose) during metabolically-matched, steady-state exercise with acute (~5 h) exposure to HA (460 mmHg) after short-term (5 days) use of Pioglitazone (HA+PIO), or matched placebo (HA+PLA). Eight healthy, recreationally active males between the ages of 18-39 yrs will be enrolled. Following a 48-hr muscle glycogen normalization period, volunteers will complete 80-min of metabolically-matched, steady-state (same absolute workload corresponding to ~55 ± 5% of V̇O2peak at HA) exercise on a treadmill, and consume 145 g of glucose (1.8 g/min) with HA+PIO and HA+PLA. A dual glucose tracer (13C-glucose oral ingestion and [6,6-2H2]-glucose primed, continuous infusion) technique and indirect calorimetry will be used to analyze endogenous and exogenous glucose oxidation, as well as glucose rate of appearance (Ra), disappearance (Rd), and MCR. Serial blood samples will be collected during each trial to assess endocrine and circulating substrate responses to exercise, carbohydrate, and hypoxia, with or without PIO. Isotope methodology and aerobic exercise protocols will be identical to our previous work (3, 4), allowing comparison of outcomes across studies. All trials will be conducted in the USARIEM hypobaric/hypoxic chamber and be separated by a minimum 10-d washout period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- randomized crossover placebo controlled double blinded study
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Experimental | Drug: Pioglitazone 15mgPioglitazone administered as a 15 mg oral dose per day for 5 days |
| Placebo | Experimental | Other: PlaceboMicrocrystalline cellulose pill administered as an oral dose per day for 5 days |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Men aged 18 - 39 years
- Born at altitudes less than 2,100 m
- Physically active (exercise minimum 2 days per week)
- Have supervisor approval (permanent party military and civilians)
- Willing to refrain from alcohol, smokeless nicotine products and dietary supplement use during study periods
Key exclusion criteria (14 listed)
- Born at altitudes greater than 2,100 m
- Musculoskeletal injuries that compromise exercise capability
- Metabolic or cardiovascular abnormalities, or gastrointestinal disorders
- Taking medication that affects macronutrient metabolism and/or the ability to participate in strenuous exercise
- Living in areas that are more than 1,200 m, or traveled to areas that are more than 1,200 m for five days or more within 2 months of data collection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pioglitazone 15mgAlso: ActosPioglitazone (PIO) will be administered as a 15 mg oral dose per day for 5 days | Drug | Pioglitazone |
| Placebo100% microcrystalline cellulos | Other | Placebo |
Primary outcome
Rate of Exogenous Glucose Oxidation
Time frame: 8 hours
Determine the effects of PIO on exogenous glucose oxidation (g/min) during exercise under acute HA exposure compared to PLA
2 secondary outcomes
Concentration of Interleukin-6
Time frame: 8 hours
Concentration of Serum Hemoglobin
Time frame: 8 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pioglitazone 15mg in people with High Altitude, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Exogenous Glucose Oxidation (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.