CD71 in Dried Blood Spots in Healthy Males

Evaluation of CD71 Expression in a Dried Blood Spot Following rEPO Administration

Understand the effect of recombinant EPO (rEPO) boosting and microdosing on the hematological module of the Athlete Biological Passport (ABP)

• Measure the change in CD71 longitudinally in subjects from both cohorts
• Assess whether rEPO administration can be detected in a dried blood spot (DBS) using recent advances in analytical methodologies
• Compare windows of rEPO detection using both Athlete Biological Passport models and direct detection using analytical methods in urine, blood, and DBS

Study Overview

• Status: Completed
• Conditions: Healthy Athletes
• Intervention / Treatment: Drug: EPOGEN® (epoetin alfa); Other: Normal Saline

Detailed Description

Despite being banned by the World Anti-Doping Agency, blood doping is a common method of performance enhancement used by athletes wishing to gain an unfair advantage over their competition. A common way to achieve this increase is by using erythropoiesis stimulating agents (ESA's), namely recombinant erythropoietin (rEPO). Though laboratory tests have been developed for the direct detection of all known isoforms of exogenously administered ESAs in both urine and blood, athletes have found ways to circumvent these testing measures using techniques such as microdosing.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Sports Medicine Research and Testing Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria: Active individuals, preferably those that participate regularly in endurance athletics either for sport or for leisure, between the ages of 18 and 45

- Participants should have ferritin > 35 ng/mL and transferrin saturation > 20% at the time of enrollment

Exclusion Criteria: Individuals currently enrolled in a registered testing pool for anti-doping purposes

• Individuals with the intent to compete in sanctioned athletic events during the study period
• Unwillingness to provide urine samples or blood samples
• Not actively exercising
• Individuals who show a high risk for MI/CAD, stroke, CHF, and venous thromboembolism (VTE)., as defined by the Principal Investigator
• Individuals with known drug allergies
• Individuals with EKG abnormalities, as determined by the Principal Investigator
• Individuals who have chronic kidney disease, HIV, cancer, hepatitis B, hepatitis C, or are planning surgery during the study
• Individuals with history of acute or chronic medical or psychiatric condition
• GFR (Creatinine clearance) <60 mL/min
• Ferritin >270 ng/mL
• Individuals who have a baseline hemoglobin concentration greater than 15.5 g/dL or a baseline hematocrit above 47%
• Individuals with blood or iron disorders, including polycythemia, hemochromatosis, anemia, or iron-deficiency anemia
• Individuals with a history of bleeding or bone marrow aplasia
• Individuals who are diabetic or with a history of cardiac or hepatic disease or history of drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort A; EPOGEN® (epoetin alfa) Study Drug Epoetin Alfa (EPOGEN®) 40 IU / kg dose during boosting phase, delivered s.c.; 8 injections 900 IU dose during microdosing, delivered i.v.; 6 injections	Drug: EPOGEN® (epoetin alfa); Active drug; Other Names: erythropoietin, rEPO
Sham Comparator: Cohort B; Saline 40 IU / kg dose during boosting phase, delivered s.c.; 8 injections 900 IU dose during microdosing, delivered i.v.; 6 injections	Other: Normal Saline; Placebo; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD71 (transferrin receptor) concentration	CD71 concentration will be measured during and following administration and will be compared to established baseline values from each individual and the study population to understand the changes caused by this dosing pattern of rEPO. These data, especially when comparing to the variability in CD71 in the placebo cohort, may be extrapolated in the anti-doping framework to detect rEPO abuse by athletes.	8 months
Hemogloblin concentration	Hemoglobin concentration will be measured during and following administration and will be compared to established baseline values from each individual and the study population to understand the changes caused by this dosing pattern of rEPO	8 months
Reticulocyte percentage (Ret%)	Ret% will be measured during and following administration and will be compared to established baseline values from each individual and the study population to understand the changes caused by this dosing pattern of rEPO	8 months
Calculated OFF-score	Calculated using the formula: OFF-score = Hgb - 60*√Ret%, OFF-score will be calculated from each collection during and following administration and will be compared to established baseline values from each individual and the study population to understand the changes caused by this dosing pattern of rEPO	8 months
Immature reticuocyte fraction	The immature reticulocyte fraction (IRF) will be measured during and following administration and will be compared to established baseline values from each individual and the study population to understand the changes caused by this dosing pattern of rEPO.	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Window of detection (detectability time) following rEPO use	The length of time (following both the subcutaneous 'boosting' phase and the intravenous 'microdosing' phase) that rEPO use is evident will be assessed. This will be assessed using different criteria: Direct detection of the rEPO drug in urine, serum (and/or plasma), and dried blood spots; b. Athlete Biological Passport adaptive model	12 months
Analytical detection of rEPO in a dried blood spot	Dried blood spot samples will be extracted and analyzed using analytical techniques (namely SAR-PAGE, SDS-PAGE, IEF-PAGE, or others) employed by the laboratory for the direct detection of rEPO.	12 months

Collaborators and Investigators

• Sponsor: Sports Medicine Research and Testing Laboratory
• Investigators: Study Director: Daniel Eichner, PhD, Sports Medicine Research and Testing Laboratory; Principal Investigator: Andre Crouch, MD, Sports Medicine Research and Testing Laboratory

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Actual): November 15, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: July 28, 2019
• First Submitted That Met QC Criteria: August 28, 2019
• First Posted (Actual): August 29, 2019

Study Record Updates

• Last Update Posted (Actual): March 17, 2021
• Last Update Submitted That Met QC Criteria: March 15, 2021
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematinics; Epoetin Alfa
• Other Study ID Numbers: SMRTL-2018_02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No