Blood DiseasePhase 3TransfusionNCT03548766
Using DNA-Typing and Erythrocyte Microparticle Analysis to Detect Blood Doping
A Phase 3 study testing Homologous Blood Transfusion and Autologous Blood Transfusion in people with Blood Disease and Blood Transfusion, Autologous, run by Hamad Medical Corporation at 1 site in Qatar.
Trial summary
A total of 12 subjects will be recruited for participation in this study. 6 subjects will receive re-infusion of autologous blood, and 6 subjects (anemic patients) will receive a homologous transfusion. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Blood Disease, Blood Transfusion, Autologous, Blood Doping
- What is being tested?
- Homologous Blood Transfusion and Autologous Blood Transfusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteQatar
- Study dates
- 20 Sep 2018to Dec 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- both genders,
- age 20-50 years and
- preferably physically active but no elite athletes subjected to Anti-Doping testing.
Who cannot join
- vulnerable subjects
- not willing to participate
- not signing the ICF
- patients with end-organ failure
Trial locations and contacts
1 site in 1 country.
Qatar1 site, 1 recruiting
- Recruiting
Hamad Medical Corporation
Doha
Mohamed Yassin
Sven Voss
About this study
Official title: Using DNA-Typing and Erythrocyte Microparticle Analysis to Detect Homologous/Autologous Blood Doping- a Transfusion Study
A total of 12 subjects will be recruited for participation in this study. 6 subjects will receive re-infusion of autologous blood, and 6 subjects (anemic patients) will receive a homologous transfusion.
Read the detailed description
Homologous blood transfusions (HBT) and autologous blood transfusions (ABT) are abused by athletes to illegally increase their hemoglobin mass and subsequently improve oxygen transport.
Anti-Doping labs use flow-cytometry to detect HBT in cheating athletes, but athletes avoid being tested positive by matching their blood for minor blood groups before transfusion. Recent publications suggest that DNA typing by Capillary Electrophoresis or RT-PCR might be an alternative way to detect this kind of doping in athletes. Unfortunately, no data exist on the clearance of DNA after transfusion of one bag of blood using this methodology.
For the detection of doping with ABT, there is no direct method available and only the biological passport, a longitudinal collection of hematological parameters can indicate doping. Recently RBC Microparticles (RBC-MPs) have been described as a potential biomarker for autologous transfusion. However, also for this methodology, no data on the clearance time of RBC-MPs are available.
Thus, in this World Anti-Doping Agency (WADA) approved and sponsored project. The investigators plan to perform a clinical trial in which six healthy subjects receive an ABT and six healthy subjects or patients a HBT. Blood samples will be collected before and at several time-points after transfusion. For the detection of HBT the samples will be analyzed by the official method (cytometry), and the two genotyping methods (STR and RT-PCR) to compare these different techniques and to see if DNA-typing can replace cytometry.
For the ABT the collected samples will be analyzed for RBC-MPs on a cytometer dedicated for Microparticles.
- Being tested
- Homologous Blood Transfusion, Autologous Blood Transfusion
- Medical subject headings
- Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Homologous Blood TransfusionBiological
Also called Allogenic Blood Transfusion
Homologous, or allogenic, blood transfusions involves someone collecting and infusing the blood of a compatible donor into him/herself.
Autologous Blood TransfusionBiological
Autologous blood transfusion is the collection and re-infusion of the patient's own blood or blood components.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Subjects | Experimental | Six healthy subjects will receive an ABT (Autologous Blood Transfusion) Receives: Biological: Autologous Blood Transfusion |
| Anemic Patients | Experimental | Six patients with anemia will receive a HBT (Homologous Blood Transfusion) Receives: Biological: Homologous Blood Transfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Donor DNA (# of loci with triplets or quadruplets):
Clearance Kinetics of donor DNA which is transferred during the transfusion of one bag of homologous blood will be established.
Measured: 12 months
Cellular Microparticles (10^3/uL):
Clearance Kinetics of cellular microparticles which are introduced during an autologous blood transfusion and are originating from red blood cells during blood storage will be established.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2018
- Study start20 Sep 2018
- Primary completionDec 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Blood DiseaseStudies of the same condition, open and under way.
- More trials run by Hamad Medical CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hamad Medical Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- World Anti-Doping Agency, Anti-Doping Lab Qatar, Sidra Medicine, Laboratorio Antidoping FMSI
- Responsible party
- Principal investigator, Dr. Mohamed A Yassin ,MD, Hamad Medical Corporation
- Investigators
- Sven Voss, Study chair, ADLQMohamed Yassin, Principal investigator, Hamad Medical CorporationFrancesco Donati, Principal investigator, Laboratorio Antidoping FMSI, Rome, ItalyCostas Georgakopoulos, Principal investigator, ADLQMohammed Alsayrafi, Principal investigator, ADLQJean-Charles Grivel, Principal investigator, Sidra MedicineChristophe Raynaud, Principal investigator, Sidra Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03548766
- Sponsor's protocol ID
- MRC-02-18-070
- Acronym
- Transfusion
- Status last verified
- Aug 2020
- First submitted
- 6 May 2018
- Last updated
- 11 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Voss SC, Thevis M, Schinkothe T, Schanzer W. Detection of homologous blood transfusion. Int J Sports Med. 2007 Aug;28(8):633-7. doi: 10.1055/s-2007-965076. Epub 2007 Jul 5.
PubMed 17614019Giraud S, Robinson N, Mangin P, Saugy M. Scientific and forensic standards for homologous blood transfusion anti-doping analyses. Forensic Sci Int. 2008 Jul 18;179(1):23-33. doi: 10.1016/j.forsciint.2008.04.007. Epub 2008 Jun 2.
PubMed 18514452Krotov G, Nikitina M, Rodchenkov G. Possible cause of lack of positive samples on homologous blood transfusion. Drug Test Anal. 2014 Nov-Dec;6(11-12):1160-2. doi: 10.1002/dta.1736. Epub 2014 Oct 20.
PubMed 25331764Donati F, Stampella A, de la Torre X, Botre F. Investigation on the application of DNA forensic human identification techniques to detect homologous blood transfusions in doping control. Talanta. 2013 Jun 15;110:28-31. doi: 10.1016/j.talanta.2013.02.042. Epub 2013 Mar 18.
PubMed 23618171Stampella A, Di Marco S, Pirri D, de la Torre X, Botre F, Donati F. Application of DNA-based forensic analysis for the detection of homologous transfusion of whole blood and of red blood cell concentrates in doping control. Forensic Sci Int. 2016 Aug;265:204-10. doi: 10.1016/j.forsciint.2016.04.021. Epub 2016 Apr 30.
PubMed 27175858Manokhina I, Rupert JL. A DNA-based method for detecting homologous blood doping. Anal Bioanal Chem. 2013 Dec;405(30):9693-701. doi: 10.1007/s00216-013-7122-8. Epub 2013 Jul 11.
PubMed 23842898Alizadeh M, Bernard M, Danic B, Dauriac C, Birebent B, Lapart C, Lamy T, Le Prise PY, Beauplet A, Bories D, Semana G, Quelvennec E. Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood. 2002 Jun 15;99(12):4618-25. doi: 10.1182/blood.v99.12.4618.
PubMed 12036896Ni W, Le Guiner C, Moullier P, Snyder RO. Development and utility of an internal threshold control (ITC) real-time PCR assay for exogenous DNA detection. PLoS One. 2012;7(5):e36461. doi: 10.1371/journal.pone.0036461. Epub 2012 May 3.
PubMed 22570718Almizraq RJ, Seghatchian J, Acker JP. Extracellular vesicles in transfusion-related immunomodulation and the role of blood component manufacturing. Transfus Apher Sci. 2016 Dec;55(3):281-291. doi: 10.1016/j.transci.2016.10.018. Epub 2016 Oct 28.
PubMed 27865649Straat M, Boing AN, Tuip-De Boer A, Nieuwland R, Juffermans NP. Extracellular Vesicles from Red Blood Cell Products Induce a Strong Pro-Inflammatory Host Response, Dependent on Both Numbers and Storage Duration. Transfus Med Hemother. 2016 Jul;43(4):302-305. doi: 10.1159/000442681. Epub 2015 Dec 16.
PubMed 27721707van der Pol E, Coumans FA, Grootemaat AE, Gardiner C, Sargent IL, Harrison P, Sturk A, van Leeuwen TG, Nieuwland R. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost. 2014 Jul;12(7):1182-92. doi: 10.1111/jth.12602. Epub 2014 Jun 19.
PubMed 24818656Nielsen MH, Beck-Nielsen H, Andersen MN, Handberg A. A flow cytometric method for characterization of circulating cell-derived microparticles in plasma. J Extracell Vesicles. 2014 Feb 4;3. doi: 10.3402/jev.v3.20795. eCollection 2014.
PubMed 24511371Rubin O, Crettaz D, Tissot JD, Lion N. Pre-analytical and methodological challenges in red blood cell microparticle proteomics. Talanta. 2010 Jun 30;82(1):1-8. doi: 10.1016/j.talanta.2010.04.025. Epub 2010 Apr 22.
PubMed 20685428Rank A, Nieuwland R, Crispin A, Grutzner S, Iberer M, Toth B, Pihusch R. Clearance of platelet microparticles in vivo. Platelets. 2011;22(2):111-6. doi: 10.3109/09537104.2010.520373. Epub 2011 Jan 13.
PubMed 21231854Voss SC, Jaganjac M, Al-Thani AM, Grivel JC, Raynaud CM, Al-Jaber H, Al-Menhali AS, Merenkov ZA, Alsayrafi M, Latiff A, Georgakopoulos C. Analysis of RBC-microparticles in stored whole blood bags - a promising marker to detect blood doping in sports? Drug Test Anal. 2017 Nov;9(11-12):1794-1798. doi: 10.1002/dta.2212. Epub 2017 Jun 20.
PubMed 28474406
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using DNA-Typing and Erythrocyte Microparticle Analysis to Detect Homologous/Autologous Blood Doping- a Transfusion Study
- ClinicalTrials.gov ID
- NCT03548766
- Acronym / sponsor ID
- Transfusion / MRC-02-18-070
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Hamad Medical CorporationIndustry (pharma, biotech, devices)
- Collaborators
- World Anti-Doping Agency, Anti-Doping Lab Qatar, Sidra Medicine, Laboratorio Antidoping FMSI
- Study start
- 20 Sep 2018 (actual)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 7 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A total of 12 subjects will be recruited for participation in this study. 6 subjects will receive re-infusion of autologous blood, and 6 subjects (anemic patients) will receive a homologous transfusion.
Detailed description
Homologous blood transfusions (HBT) and autologous blood transfusions (ABT) are abused by athletes to illegally increase their hemoglobin mass and subsequently improve oxygen transport.
Anti-Doping labs use flow-cytometry to detect HBT in cheating athletes, but athletes avoid being tested positive by matching their blood for minor blood groups before transfusion. Recent publications suggest that DNA typing by Capillary Electrophoresis or RT-PCR might be an alternative way to detect this kind of doping in athletes. Unfortunately, no data exist on the clearance of DNA after transfusion of one bag of blood using this methodology.
For the detection of doping with ABT, there is no direct method available and only the biological passport, a longitudinal collection of hematological parameters can indicate doping. Recently RBC Microparticles (RBC-MPs) have been described as a potential biomarker for autologous transfusion. However, also for this methodology, no data on the clearance time of RBC-MPs are available.
Thus, in this World Anti-Doping Agency (WADA) approved and sponsored project. The investigators plan to perform a clinical trial in which six healthy subjects receive an ABT and six healthy subjects or patients a HBT. Blood samples will be collected before and at several time-points after transfusion. For the detection of HBT the samples will be analyzed by the official method (cytometry), and the two genotyping methods (STR and RT-PCR) to compare these different techniques and to see if DNA-typing can replace cytometry.
For the ABT the collected samples will be analyzed for RBC-MPs on a cytometer dedicated for Microparticles.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Subjects | Experimental | Biological: Autologous Blood TransfusionSix healthy subjects will receive an ABT (Autologous Blood Transfusion) |
| Anemic Patients | Experimental | Biological: Homologous Blood TransfusionSix patients with anemia will receive a HBT (Homologous Blood Transfusion) |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- both genders,
- age 20-50 years and
- preferably physically active but no elite athletes subjected to Anti-Doping testing.
Key exclusion criteria (4 listed)
- vulnerable subjects
- not willing to participate
- not signing the ICF
- patients with end-organ failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Homologous Blood TransfusionAlso: Allogenic Blood TransfusionHomologous, or allogenic, blood transfusions involves someone collecting and infusing the blood of a compatible donor into him/herself. | Biological | Anemic Patients |
| Autologous Blood TransfusionAutologous blood transfusion is the collection and re-infusion of the patient's own blood or blood components. | Biological | Healthy Subjects |
Primary outcome
Donor DNA (# of loci with triplets or quadruplets):
Time frame: 12 months
Clearance Kinetics of donor DNA which is transferred during the transfusion of one bag of homologous blood will be established.
Cellular Microparticles (10^3/uL):
Time frame: 12 months
Clearance Kinetics of cellular microparticles which are introduced during an autologous blood transfusion and are originating from red blood cells during blood storage will be established.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- Background: PubMed 17614019Voss SC, Thevis M, Schinkothe T, Schanzer W. Detection of homologous blood transfusion. Int J Sports Med. 2007 Aug;28(8):633-7. doi: 10.1055/s-2007-965076. Epub 2007 Jul 5.
- Background: PubMed 18514452Giraud S, Robinson N, Mangin P, Saugy M. Scientific and forensic standards for homologous blood transfusion anti-doping analyses. Forensic Sci Int. 2008 Jul 18;179(1):23-33. doi: 10.1016/j.forsciint.2008.04.007. Epub 2008 Jun 2.
- Background: PubMed 25331764Krotov G, Nikitina M, Rodchenkov G. Possible cause of lack of positive samples on homologous blood transfusion. Drug Test Anal. 2014 Nov-Dec;6(11-12):1160-2. doi: 10.1002/dta.1736. Epub 2014 Oct 20.
- Background: PubMed 23618171Donati F, Stampella A, de la Torre X, Botre F. Investigation on the application of DNA forensic human identification techniques to detect homologous blood transfusions in doping control. Talanta. 2013 Jun 15;110:28-31. doi: 10.1016/j.talanta.2013.02.042. Epub 2013 Mar 18.
- Background: PubMed 27175858Stampella A, Di Marco S, Pirri D, de la Torre X, Botre F, Donati F. Application of DNA-based forensic analysis for the detection of homologous transfusion of whole blood and of red blood cell concentrates in doping control. Forensic Sci Int. 2016 Aug;265:204-10. doi: 10.1016/j.forsciint.2016.04.021. Epub 2016 Apr 30.
- Background: PubMed 23842898Manokhina I, Rupert JL. A DNA-based method for detecting homologous blood doping. Anal Bioanal Chem. 2013 Dec;405(30):9693-701. doi: 10.1007/s00216-013-7122-8. Epub 2013 Jul 11.
- Background: PubMed 12036896Alizadeh M, Bernard M, Danic B, Dauriac C, Birebent B, Lapart C, Lamy T, Le Prise PY, Beauplet A, Bories D, Semana G, Quelvennec E. Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood. 2002 Jun 15;99(12):4618-25. doi: 10.1182/blood.v99.12.4618.
- Background: PubMed 22570718Ni W, Le Guiner C, Moullier P, Snyder RO. Development and utility of an internal threshold control (ITC) real-time PCR assay for exogenous DNA detection. PLoS One. 2012;7(5):e36461. doi: 10.1371/journal.pone.0036461. Epub 2012 May 3.
- Background: PubMed 27865649Almizraq RJ, Seghatchian J, Acker JP. Extracellular vesicles in transfusion-related immunomodulation and the role of blood component manufacturing. Transfus Apher Sci. 2016 Dec;55(3):281-291. doi: 10.1016/j.transci.2016.10.018. Epub 2016 Oct 28.
- Background: PubMed 27721707Straat M, Boing AN, Tuip-De Boer A, Nieuwland R, Juffermans NP. Extracellular Vesicles from Red Blood Cell Products Induce a Strong Pro-Inflammatory Host Response, Dependent on Both Numbers and Storage Duration. Transfus Med Hemother. 2016 Jul;43(4):302-305. doi: 10.1159/000442681. Epub 2015 Dec 16.
- Background: PubMed 24818656van der Pol E, Coumans FA, Grootemaat AE, Gardiner C, Sargent IL, Harrison P, Sturk A, van Leeuwen TG, Nieuwland R. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost. 2014 Jul;12(7):1182-92. doi: 10.1111/jth.12602. Epub 2014 Jun 19.
- Background: PubMed 24511371Nielsen MH, Beck-Nielsen H, Andersen MN, Handberg A. A flow cytometric method for characterization of circulating cell-derived microparticles in plasma. J Extracell Vesicles. 2014 Feb 4;3. doi: 10.3402/jev.v3.20795. eCollection 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sven Voss study chair
ADLQ
Mohamed Yassin principal investigator
Hamad Medical Corporation
Francesco Donati principal investigator
Laboratorio Antidoping FMSI, Rome, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Homologous Blood Transfusion and Autologous Blood Transfusion in people with Blood Disease and Blood Transfusion, Autologous, run by Hamad Medical Corporation at 1 site in Qatar.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Qatar. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sven C Voss (0097455481955, svoss@adlqatar.qa), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Donor DNA (# of loci with triplets or quadruplets): (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03548766, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2020.