Impact of Erythropoietin on Hematological Adaptations and Physical Performance

NCT05078138 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 20-01H
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Exercise-Induced Anemia; Physical Performance

Outcome Measures

Primary Outcomes (2)

• Concentration of Hemoglobin

  Determine the effects of EPO on hemoglobin concentration compared to baseline during 4 weeks of overtraining.

  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.

  4 weeks

Secondary Outcomes (1)

• Rate of Fat Oxidation

  4 weeks

Study Arms (1)

Exogenous Erythropoietin

EXPERIMENTAL

Recombinant human Erythropoietin subcutaneous injection of 50 IU/kg body mass 3 times per week for 4 week

Drug: Epoetin Alfa

Interventions

Epoetin Alfa DRUG

Subcutaneous injection of Epoetin Alfa 3 times per week for 4 weeks

Exogenous Erythropoietin

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• United States Army Research Institute of Environmental Medicine: lead

Study Sites (1)

US Army Research Institute of Environmental Medicine

Natick, Massachusetts, 01760, United States

Location

MeSH Terms

Interventions

Epoetin Alfa

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Lee Margolis
• Organization: USARIEM

lee.m.margolis.civ@health.mil

508-206-2335

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Longitudinal study design

Study Record Dates

• First Submitted: August 6, 2021
• First Posted: October 14, 2021
• Study Start: September 1, 2021
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: April 18, 2025
• Results First Posted: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)