Detecting Autologous Transfusion by Measuring Alterations in the Dynamics of Red Blood Cell Maturation and Recycling

Blood Transfusion, Autologous Clinical Trial

Official title:

Detecting Autologous Transfusion by Measuring Alterations in the Dynamics of Red Blood Cell Maturation and Recycling

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02684747
• Other study ID #: 83533
• Status: Completed
• Phase: Early Phase 1
• Start date: February 2016
• Est. completion date: May 5, 2018

Study information

• Verified date: May 2018
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 5, 2018
• Est. primary completion date: May 5, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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/QuestionsaboutB lood/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

Related Conditions & MeSH terms

• Blood Doping
• Blood Transfusion, Autologous

Intervention

Other:
• Autologous Transfusion
Participants will receive autologous transfusion on Day 21
• Control - Normal Saline (Placebo)
Participants will receive saline on Day 21

Locations

Country	Name	City	State
United States	University of Utah Center for Clinical & Translational Science	Salt Lake City	Utah

Sponsors (3)

Lead Sponsor	Collaborator
University of Utah	Partnership for Clean Competition, Sports Medicine Research and Testing Laboratory

Country where clinical trial is conducted

United States, 

References & Publications (11)

Basson, M. Red blood cells by the numbers. Nature Medicine 16, 1 (2010).

Cowell HR, Swickard JW. Autotransfusion in children's orthopaedics. J Bone Joint Surg Am. 1974 Jul;56(5):908-12. — View Citation

Cregan P, Donegan E, Gotelli G. Hemolytic transfusion reaction following transfusion of frozen and washed autologous red cells. Transfusion. 1991 Feb;31(2):172-5. — View Citation

Domen RE. Adverse reactions associated with autologous blood transfusion: evaluation and incidence at a large academic hospital. Transfusion. 1998 Mar;38(3):296-300. — View Citation

Higgins JM, Mahadevan L. Physiological and pathological population dynamics of circulating human red blood cells. Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20587-92. doi: 10.1073/pnas.1012747107. Epub 2010 Nov 8. — View Citation

Kumar S, Goyal K, Dubey S, Bindra A, Kedia S. Anaphylactic reaction after autologous blood transfusion: A case report and review of the literature. Asian J Neurosurg. 2015 Apr-Jun;10(2):145-7. doi: 10.4103/1793-5482.154983. — View Citation

Mørkeberg J, Belhage B, Ashenden M, Bornø A, Sharpe K, Dziegiel MH, Damsgaard R. Screening for autologous blood transfusions. Int J Sports Med. 2009 Apr;30(4):285-92. doi: 10.1055/s-0028-1105938. Epub 2009 Feb 6. — View Citation

Popovsky MA, Whitaker B, Arnold NL. Severe outcomes of allogeneic and autologous blood donation: frequency and characterization. Transfusion. 1995 Sep;35(9):734-7. — View Citation

Pottgiesser T, Sottas PE, Echteler T, Robinson N, Umhau M, Schumacher YO. Detection of autologous blood doping with adaptively evaluated biomarkers of doping: a longitudinal blinded study. Transfusion. 2011 Aug;51(8):1707-15. doi: 10.1111/j.1537-2995.2011.03076.x. Epub 2011 Mar 7. — View Citation

Solymos E, Guddat S, Geyer H, Flenker U, Thomas A, Segura J, Ventura R, Platen P, Schulte-Mattler M, Thevis M, Schänzer 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. — View Citation

Weatherall DJ. Systems biology and red cells. N Engl J Med. 2011 Jan 27;364(4):376-7. doi: 10.1056/NEJMcibr1012683. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematocrit	This will be used within a mathematical model to define the volume (v) and hemoglobin (h) dynamics of a typical RBC as deterministic functions (f) and random fluctuations in the rates of these changes over time (?) (Patel, Patel, & Higgins, 2015).	8 weeks
Primary	Hemoglobin	This will be used within a mathematical model to define the volume (v) and hemoglobin (h) dynamics of a typical RBC as deterministic functions (f) and random fluctuations in the rates of these changes over time (?) (Patel, Patel, & Higgins, 2015).	8 weeks
Primary	Reticulocyte count	This will be used within a mathematical model to define the volume (v) and hemoglobin (h) dynamics of a typical RBC as deterministic functions (f) and random fluctuations in the rates of these changes over time (?) (Patel, Patel, & Higgins, 2015).	8 weeks
Primary	Mean corpuscular volume	This will be used within a mathematical model to define the volume (v) and hemoglobin (h) dynamics of a typical RBC as deterministic functions (f) and random fluctuations in the rates of these changes over time (?) (Patel, Patel, & Higgins, 2015).	8 weeks