MedPath

CD71 in Dried Blood Spots in Healthy Males

Early Phase 1
Completed
Conditions
Healthy Athletes
Interventions
Other: Normal Saline
Registration Number
NCT04073849
Lead Sponsor
Sports Medicine Research and Testing Laboratory
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
24
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort AEPOGEN® (epoetin alfa)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
Cohort BNormal SalineSaline 40 IU / kg dose during boosting phase, delivered s.c.; 8 injections 900 IU dose during microdosing, delivered i.v.; 6 injections
Primary Outcome Measures
NameTimeMethod
Reticulocyte percentage (Ret%)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 fraction8 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) concentration8 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 concentration8 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-score8 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 Outcome Measures
NameTimeMethod
Window of detection (detectability time) following rEPO use12 months

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:

1. Direct detection of the rEPO drug in urine, serum (and/or plasma), and dried blood spots

2. b. Athlete Biological Passport adaptive model

Analytical detection of rEPO in a dried blood spot12 months

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.

Trial Locations

Locations (1)

Sports Medicine Research and Testing Laboratory

🇺🇸

Salt Lake City, Utah, United States

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