Clinical trial NCT02684747: Detecting Autologous Transfusion by Measuring Alterations in the Dynamics of Red Blood Cell Maturation and Recycling
Official title: Detecting Autologous Transfusion by Measuring Alterations in the Dynamics of Red Blood Cell Maturation and Recycling
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Blood Transfusion, Autologous
Blood Doping
Keywords: Healthy Volunteers
Sports Medicine
Athletes
Anti-doping
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Sports Medicine Research and Testing Laboratory
name: Partnership for Clean Competition
First posted: 2016-02-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: A total of 40 subjects will be recruited for participation in this study. 20 subjects (10 males and 10 females) will be randomized to the active group (those receiving re-infusion of autologous blood) and 20 subjects (10 males and 10 females) will be randomized to the placebo group (receiving NS infusion).

Detailed description: Autologous blood transfusion is a major problem in a wide range of competitive sports. Methods with increased sensitivity, specificity, and feasibility are needed to identify athletes who cheat in this manner and compromise their health and the integrity of their sports in general. Complete blood counts (CBC) offer routine high-resolution assessment of the current hematologic status of individuals, providing estimates of a number of blood characteristics, such as the total hemoglobin concentration in the blood (HGB) and the volume fraction of cells in the blood (HCT). These CBC components are homeostatically controlled by the carefully regulated dynamic processes of red blood cell (RBC) production in and release from the bone marrow, RBC maturation in the peripheral circulation over the course of the \~100-day RBC lifespan, and clearance and recycling of senescent cells. Any significant perturbation to the circulating population of RBCs, like autologous transfusion, will immediately trigger compensatory modulation of one or more of these dynamic processes. The investigators believe quantification of these underlying dynamic processes will enable us to detect autologous transfusion. These dynamic RBC processes cannot currently be measured directly, but novel mathematical modeling enables their inference from routine complete blood and reticulocyte counts. The investigators propose to test the ability of modeled RBC dynamics to identify instances of autologous blood transfusion.

Eligibility criteria: Inclusion Criteria:

1. Male or female between 18-35 years old
2. Classified as low risk and will not have any major signs or symptoms suggestive of cardiovascular, pulmonary, or metabolic disease according to the American College of Sports Medicine's (ACSM) risk stratification categories
3. The subjects should be well-trained endurance athletes. This group could consist of cyclists (road and mountain), triathletes, runners, long-distance swimmers, etc.

Exclusion Criteria:

1. Age less than 18 or greater than 35 on the day of enrollment
2. Any contraindication to blood donation as defined by the American Association of Blood Banks http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/QuestionsaboutBlood/UCM272981.pdf
3. Any chronic illness (e.g.diabetes, heart disease, hypotension, anemia, hemoglobinopathy, marrow diseases, leukemia/lymphoma, pregnancy, amenorrhea/female athlete triad)
4. Any abnormal CBC index or iron study; any blood dyscrasia
5. Abnormal blood and urine tests for doping agents (e.g. phthalates)
6. Positive uhCG or women who are attempting to get pregnant during the study period
7. Unwilling or unable to provide blood samples or receive a blood transfusion
8. Not a participant in endurance sports activities
9. Are currently on any medications that might affect hematologic parameters including, but not restricted to, hematopoietic medications
10. Subjects with a baseline hemoglobin above 16.7 g/dL, or baseline hematocrit below 35% or above 55%.
11. Any subject that plans to participate in an organized athletic event (or USA Cycling sanctioned event) within 30 days following the re-infusion phase of the study will not be allowed to participate in the study

Primary outcomes:
measure: Hematocrit
timeFrame: 8 weeks
measure: Hemoglobin
timeFrame: 8 weeks
measure: Reticulocyte count
timeFrame: 8 weeks
measure: Mean corpuscular volume
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah Center for Clinical & Translational Science
state: Utah
Study officials:
affiliation: University of Utah
name: Daniel Cushman, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Solymos E, Guddat S, Geyer H, Flenker U, Thomas A, Segura J, Ventura R, Platen P, Schulte-Mattler M, Thevis M, Schanzer W. Rapid determination of urinary di(2-ethylhexyl) phthalate metabolites based on liquid chromatography/tandem mass spectrometry as a marker for blood transfusion in sports drug testing. Anal Bioanal Chem. 2011 Aug;401(2):517-28. doi: 10.1007/s00216-010-4589-4. Epub 2010 Dec 25.
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