Effects of Pioglitazone on Exogenous Carbohydrate Oxidation During Steady-State Exercise at High Altitude
Condition: High Altitude
MeSH terms: Altitude Sickness
Study type: Interventional
Phase: Phase 4

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. 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.
    

Intervention name(s): Pioglitazone 15mg; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Pioglitazone (PIO) will be administered as a 15 mg oral dose per day for 5 days; 100% microcrystalline cellulos
Other intervention name(s): Actos
Intervention MeSH terms: Pioglitazone
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: randomized crossover placebo controlled double blinded study
Masking: Double (Participant, Investigator)
Primary purpose: Treatment