Exercise-Induced AnemiaPhase 4NCT05078138
Impact of Erythropoietin on Hematological Adaptations and Physical Performance
A Phase 4 study testing Epoetin Alfa in people with Exercise-Induced Anemia and Physical Performance, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
Trial summary
Negative hematological adaptations due to prolonged periods of strenuous physical activity may, in part, contribute to declines in physical performance during military operations. Read more about this study
- Who is it for?
- Ages 18 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Exercise-Induced Anemia, Physical Performance
- What is being tested?
- Epoetin Alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2021to 1 Apr 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women aged 18 - 39 years
- Weight stable (±5 lbs) for at least 2 months prior to the start of the study
- Body mass index (BMI) between 18.5-30 kg/m2
- Recreationally active (minimum 2-4 days per week aerobic and/or resistance exercise)
- Refrain from taking any NSAIDS (i.e., 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)
- Refrain from the use of alcohol and nicotine while on study diets
- Supervisor approval for federal civilian employees working within the US Army Natick Soldier Systems Center
Who cannot join
- Metabolic or cardiovascular abnormalities, gastrointestinal disorders (i.e., kidney disease, diabetes, cardiovascular disease, hypertension etc.)
- Personnel or family history of blood clots
- Disease or medication (i.e., diabetes medications, statins, corticosteroids, etc) that affects macronutrient utilization and/or the ability to participate in strenuous exercise
- Allergies or intolerance to foods (including but not limited to lactose intolerance/milk allergy), vegetarian practices, or medications (including, but not limited to, lidocaine or phenylalanine) to be utilized in the study
- History of inflammatory bowel disease
- History of seizures
Show all 15Show fewer
- Anemia (HCT < 38) and Sickle Cell Anemia/Trait
- Abnormal PT/PTT test or problems with blood clotting
- Present condition of alcoholism, use of nutritional/sports supplements, anabolic steroids, or other substance abuse issues
- History of malignancy
- Use of oral contraceptives or hormone replacement therapy due to increased risk of clotting
- Musculoskeletal injuries that compromise the ability to exercise
- Blood donation within 8 weeks of beginning the study
- Are unwilling or unable to eat study diets and foods provided and/or follow exercise prescriptions
- Pregnancy, post-partum status, or breastfeeding
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
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.
Read the 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.
- Conditions
- Exercise-Induced Anemia, Physical Performance
- Being tested
- Epoetin Alfa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epoetin AlfaDrug
Subcutaneous injection of Epoetin Alfa 3 times per week for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Exogenous Erythropoietin | Experimental | Recombinant human Erythropoietin subcutaneous injection of 50 IU/kg body mass 3 times per week for 4 week Receives: Drug: Epoetin Alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of Hemoglobin
Determine the effects of EPO on hemoglobin concentration compared to baseline during 4 weeks of overtraining.
Measured: 4 weeks
Time to Complete 5 km Time Trial
Determine the time course change in time to complete a 5 km treadmill run with EPO compared to baseline.
Measured: 4 weeks
Secondary outcomes (1)
Rate of Fat Oxidation
Assess the influence of EPO non-hematological adaptation (carbohydrate and fat oxidation rates and skeletal muscle substrate oxidation and glucose turnover rates) following 4 weeks of overtraining compared to baseline.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2021
- Study start1 Sep 2021
- Primary completion1 Apr 2023
- Study completion1 Apr 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Exercise-Induced AnemiaStudies 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Longitudinal study design
- Masking
- None (open label)
- Enrolment
- 8 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
- NCT05078138
- Sponsor's protocol ID
- 20-01H
- Status last verified
- Apr 2025
- First submitted
- 6 Aug 2021
- Last updated
- 18 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Drummer DJ, McNiff JL, Howard EE, Gwin JA, Carrigan CT, Murphy NE, Wilson MA, Michalak J, Ryan BJ, McClung JP, Pasiakos SM, Margolis LM. Exogenous erythropoietin increases hematological status, fat oxidation, and aerobic performance in males following prolonged strenuous training. Physiol Rep. 2024 May;12(10):e16038. doi: 10.14814/phy2.16038.
PubMed 38757249
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Erythropoietin on Hematological Adaptations and Physical Performance
- ClinicalTrials.gov ID
- NCT05078138
- Acronym / sponsor ID
- 20-01H
- Conditions
- Exercise-Induced Anemia, Physical Performance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- United States Army Research Institute of Environmental MedicineUS federal agency
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 1 Apr 2023 (actual)
- Study completion
- 1 Apr 2023 (actual)
- First posted
- 14 Oct 2021 (actual)
- Results
- Posted 18 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Longitudinal study design
| Arm | Type | Receives |
|---|---|---|
| Exogenous Erythropoietin | Experimental | Drug: Epoetin AlfaRecombinant human Erythropoietin subcutaneous injection of 50 IU/kg body mass 3 times per week for 4 week |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Men and women aged 18 - 39 years
- Weight stable (±5 lbs) for at least 2 months prior to the start of the study
- Body mass index (BMI) between 18.5-30 kg/m2
- Recreationally active (minimum 2-4 days per week aerobic and/or resistance exercise)
- Refrain from taking any NSAIDS (i.e., 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)
Key exclusion criteria (15 listed)
- Metabolic or cardiovascular abnormalities, gastrointestinal disorders (i.e., kidney disease, diabetes, cardiovascular disease, hypertension etc.)
- Personnel or family history of blood clots
- Disease or medication (i.e., diabetes medications, statins, corticosteroids, etc) that affects macronutrient utilization and/or the ability to participate in strenuous exercise
- Allergies or intolerance to foods (including but not limited to lactose intolerance/milk allergy), vegetarian practices, or medications (including, but not limited to, lidocaine or phenylalanine) to be utilized in the study
- History of inflammatory bowel disease
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 |
|---|---|---|
| Epoetin AlfaSubcutaneous injection of Epoetin Alfa 3 times per week for 4 weeks | Drug | Exogenous Erythropoietin |
Primary outcome
Concentration of Hemoglobin
Time frame: 4 weeks
Determine the effects of EPO on hemoglobin concentration compared to baseline during 4 weeks of overtraining.
Time to Complete 5 km Time Trial
Time frame: 4 weeks
Determine the time course change in time to complete a 5 km treadmill run with EPO compared to baseline.
1 secondary outcome
Rate of Fat Oxidation
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38757249Drummer DJ, McNiff JL, Howard EE, Gwin JA, Carrigan CT, Murphy NE, Wilson MA, Michalak J, Ryan BJ, McClung JP, Pasiakos SM, Margolis LM. Exogenous erythropoietin increases hematological status, fat oxidation, and aerobic performance in males following prolonged strenuous training. Physiol Rep. 2024 May;12(10):e16038. doi: 10.14814/phy2.16038.
- Individual participant dataSharing planned: No
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 Epoetin Alfa in people with Exercise-Induced Anemia and Physical Performance, 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 7 inclusion and 15 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 18 Apr 2025. 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 18 Apr 2025). 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?
Concentration of Hemoglobin (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05078138, which also lists 1 linked publication.
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 18 Apr 2025.