Evaluation of CD71 Expression in a Dried Blood Spot Following rEPO Administration
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Completed
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Reticulocyte percentage (Ret%)
Study Overview
Brief Summary
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
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Single (Participant)
Masking Description
Online randomization tool
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
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
Intervention: EPOGEN® (epoetin alfa) (Drug)
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
Intervention: Normal Saline (Other)
Outcomes
Primary Outcomes
Reticulocyte percentage (Ret%)
Time Frame: 8 months
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
Immature reticuocyte fraction
Time Frame: 8 months
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.
CD71 (transferrin receptor) concentration
Time Frame: 8 months
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.
Hemogloblin concentration
Time Frame: 8 months
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
Calculated OFF-score
Time Frame: 8 months
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
Secondary Outcomes
- Window of detection (detectability time) following rEPO use(12 months)
- Analytical detection of rEPO in a dried blood spot(12 months)