Impact of Erythropoietin on Hematological Adaptations and Physical Performance
Condition: Exercise-Induced Anemia; Physical Performance
Study type: Interventional
Phase: Phase 4

Summary: 
      Negative hematological adaptations due to prolonged periods of strenuous physical activity
      may, in part, contribute to declines in physical performance during military operations.
      Exogenous erythropoietin (EPO) is a potential intervention that may be used to maintain
      hemoglobin (hgb), hematocrit (Hct), and physical performance during periods of high physical
      activity. The objective of the current study is to determine the ability of EPO to maintain
      hgb, Hct, and physical performance compared to baseline measures. Additionally, EPO may
      result in non-hematological adaptations which increase mitochondria biogenesis and alter
      substrate oxidation. As such, this study will also assess the influence of EPO on whole-body
      and skeletal muscle substrate oxidation. Eight healthy physically active individuals will be
      recruited to participate in this longitudinal trial. After exercise practice sessions,
      volunteers will complete baseline physical performance (time trial) and substrate oxidation
      testing. Participants will then receive EPO injections 3 times per week for 4 weeks. Diet and
      exercise will be controlled during the injection period. Participants will undergo four weeks
      of an intense physical training exercise program. Every seventh day during the injection
      period a safety blood sample, assessing hematocrit, will be drawn, and participants will
      complete a 5 km time trial to determine the time course of changes in physical performance
      can be detected. After the 4 weeks of EPO injections volunteers will complete the same
      physical performance and substrate oxidation testing. Substrate oxidation will be assessed
      during 90-min steady-state load carriage (30% body mass) exercise on a treadmill at 55 ± 5%
      of VO2peak. 6-6-[2H2] glucose tracer technique and indirect calorimetry will be used measure
      substrate oxidation. Muscle biopsies will be performed to measure muscle glycogen, enzyme
      activity, and molecular markers of metabolism and inflammation before, and immediately and
      3-hrs post exercise. Multiple blood samples will be collected throughout the study to
      determine alterations in hemoglobin, hematocrit, and markers of substrate metabolism, and
      inflammation. All study procedures will occur at USARIEM. The primary risks associated with
      this study include those associated with EPO injection, exercise, blood draws, and muscle
      biopsies.
    

Detailed description: 
      Healthy physically active individuals will be recruited to participate in this longitudinal
      trial. After baseline assessments of body composition, resting metabolic rate (RMR), VO2peak
      and exercise familiarization; volunteers will complete physical performance and substrate
      oxidation testing. Physical performance will be assessed using time trial. Substrate
      oxidation will be assessed by volunteers performing 90-min of steady-state load carriage (30%
      body mass) exercise on a treadmill at 55 ± 5% of their VO2peak. 6-6-[2H2] glucose will be
      used as a tracer to assess glucose turnover. Indirect calorimetry will be used to determine
      carbohydrate and fat oxidation. Muscle biopsies will be performed to measure muscle glycogen,
      enzyme activity, and molecular markers of substrate metabolism before, immediately after, and
      3-hrs post exercise. Multiple blood samples will be collected on substrate oxidation protocol
      days. To minimize carry over effects of muscle biopsies on subsequent exercise performance,
      volunteers will not exercise for 3 days. During the first two days of this period, volunteers
      will undergo carbon monoxide (CO) rebreathing to measure Hgb mass and blood volume.
      Volunteers will then receive EPO injections 3 times a week for 4 weeks. During the injection
      period all volunteers will have safety blood draws to assess Hct once a week. Volunteers will
      also complete a physical performance test once a week to determine time course change in
      performance with EPO compared to baseline. Exercise training will be controlled during the
      injection phase, consisting of a combination of endurance- and resistance-type exercise.
      During the final week of the injection phase body composition, resting metabolic rate (RMR)
      and VO2peak will be reassessed. At the end of the 4-week injection phase volunteers will
      complete a final physical performance test and substrate oxidation protocol, followed by two
      CO rebreathing tests on subsequent days. All food and beverages (except water) will be
      provided to volunteers beginning at the pre injection physical performance and substrate
      oxidation through the duration of the study. All data collection will occur at USARIEM.
    

Intervention name(s): Epoetin Alfa
Intervention type(s): Drug
Intervention description(s): Subcutaneous injection of Epoetin Alfa 3 times per week for 4 weeks
Intervention MeSH terms: Epoetin Alfa
Intervention model: Sequential Assignment
Intervention model description: Longitudinal study design
Masking: None (Open Label)
Primary purpose: Prevention