Tracing Changed Production of Red Blood Cells

Study Overview
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Brief Summary
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In competitive sport, it is illegal to manipulate erythropoiesis. Manipulated erythropoiesis can indirectly be identified by atypical fluctuations in key haematological variables. However, this method also has limitations and as it is known that some athletes still manipulate erythropoiesis it is necessary to develop new and more sensitive detection methods. The primary purpose of the study is to examine the importance of altered erythropoiesis for surface and intracellular erythrocyte proteins, the number of immature reticulocytes, and for the haematological characteristics of the erythrocyte, such as volume, haemoglobin concentration and concentration of glycosylated haemoglobin, to assess whether these can be used to identify changed erythropoiesis. Furthermore, the aim is to examine whether these parameters are affected by freezer storage of erythrocytes.

Official Title
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Tracing Changed Production of Red Blood Cells

Conditions
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Erythrocytosis, Erythropoiesis Abnormal

Intervention / Treatment
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* Drug: Recombinant human erythropoietin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men 18-40 years physical fitness rating more than 50ml/kg/min non-smokers blood pressure <130/90 mmHg hemoglobin concentration 7-10.5 mM. Exclusion Criteria: Blood donor who has donated blood within the last three months Participation in other concurrent clinical trials To participate in competitive sport during or three months after the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Recombinant human erythropoietin treatment three times per week for three weeks | Drug: Recombinant human erythropoietin<br>* Recombinant human erythropoietin treatment three times per week for three weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in CD71 expression | Treatment induced changes in CD71 expression on red blood cells | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in CD35 expression | Treatment induced changes in CD35 expression on red blood cells | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in CD47 expression | Treatment induced changes in CD47 expression on red blood cells | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in CD55 expression | Treatment induced changes in CD55 expression on red blood cells | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in CD59 expression | Treatment induced changes in CD59 expression on red blood cells | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in RNA expression | Treatment induced changes in RNA expression in red blood cells | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in Mean Cell Volume | Treatment induced changes in Mean Cell Volume distribution of red blood cells | In the period from two weeks before treatment to three weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in HbA1c | Treatment induced changes in HbA1c content of red blood cells | In the period from two weeks before treatment to three weeks after treatment | 
| Continous blood glucose levels | Continuous blood glucose level throughout the study | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in CD71 cryopreserved | CD71 expression on red blood cells before and after cryopreservation | Cryopreserved cells are measured 6 months after sample collection | 
| Changes in CD35 cryopreserved | CD35 expression on red blood cells before and after cryopreservation | Cryopreserved cells are measured 6 months after sample collection | 
| Changes in CD47 cryopreserved | CD47 expression on red blood cells before and after cryopreservation | Cryopreserved cells are measured 6 months after sample collection | 
| Changes in CD55 cryopreserved | CD55 expression on red blood cells before and after cryopreservation | Cryopreserved cells are measured 6 months after sample collection | 
| Changes in CD59 cryopreserved | CD59 expression on red blood cells before and after cryopreservation | Cryopreserved cells are measured 6 months after sample collection | 
| Changes in RNA cryopreserved | RNA expression inred blood cells before and after cryopreservation | Cryopreserved cells are measured 6 months after sample collection | 
| Changes in Mean Cell Volume cryopreserved | Mean Cell Volume distribution of red blood cells before and after cryopreservation | Cryopreserved cells are measured 6 months after sample collection | 
| Changes in Ferritin | Quantification of plasma ferritin concentration | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in Complete Blood Count on Advia | Complete Blood Count analysis on the Advia 2120i instrument | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in Complete Blood Count on Sysmex | Complete Blood Count analysis on the Sysmex XN-450 instrument | In the period from two weeks before treatment to three weeks after treatment | 
| Changes in Complete Blood Count on Advia - cryopreserved | Complete Blood Count analysis on the Advia 2120i instrument before and after cryopreservation | Cryopreserved cells are measured 6 months after sample collection | 
| Changes in Complete Blood Count on Sysmex - cryopreserved | Complete Blood Count analysis on the Sysmex XN-450 instrument before and after cryopreservation | Cryopreserved cells are measured 6 months after sample collection | 
| Changes in ALAS 2 | Quantification of ALAS 2 in dried blood spots stored at room temperature, -20C and -80C | Up to 5 years | 
| Changes in CA1 | Quantification of CA1 in dried blood spots | Up to 5 years | 
| Changes in SLC4a1 | Quantification of SLC4a1 in dried blood spots | Up to 5 years | 
| Changes in CD71 in dried blood spots | Quantification of CD71 in dried blood spots | Up to 5 years | 
| Changes in FECH | Quantification of FECH in dried blood spots | Up to 5 years | 
| Changes in Band 3 | Quantification of Band 3 in dried blood spots | Up to 5 years | 
| Changes in blood volume | Measurement of blood volume by CO rebreathing | Within 14 days before treatment and within 14 days after treatment |