Infusion of a Single Dose of Erythropoietin to Prevent Injury in an Ischemia Reperfusion Forearm Model

Study Overview
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Brief Summary
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Rationale: The investigators hypothesize that EPO protects against apoptosis after acute ischemia in man and that it is detectable using the annexin-A5 model. Objective: Does infusion of a single dose of Epoetin Alfa, a short-acting EPO, protect against apoptosis in man after acute ischemia? Study design: A double blinded randomised cross-over study. Study population: 12 Healthy male volunteers, between 18 and 40 years old. Intervention: All 12 volunteers will receive a single dose of EPO and placebo in a randomized order. A six week wash-out period is obtained in order to avoid interference of both treatments. Main study parameters/endpoints: The percentage of difference between radioactivity (quantified as counts per pixel) of the experimental and control thenar muscle at one and four hours after reperfusion.

Official Title
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Infusion of a Single Dose of Erythropoietin to Prevent Injury in an Ischemia Reperfusion Forearm Model - A Randomised Cross-over Study to Evaluate if Infusion of a Single Dose of EPO Protects Against Ischemia-reperfusion Injury in Man

Conditions
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Ischemia-Reperfusion Injury, Myocardial Infarction

Intervention / Treatment
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* Drug: Epoetin alpha
* Drug: NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers between 18 and 40 years of age male Volunteers are not allowed smoking 24 hours before the start of the experiment Exclusion Criteria: Female Hypertension (SBP >140 mmHg, DBP >90 mmHg) Diabetes Mellitus (DM) (fasting glc >6.9 mmol/l, glc >11.0 mmol/l) Hypercholesterolemia Renal dysfunction (eGFR < 60 ml/min, calculated using MDRD formula) Any known hypersensitivity/allergic reaction to one of the constituents of Epoetin Alfa A history of use of any form of EPO Any current medication use Cardiovascular disease in medical history Smoking less than 24 hours prior to Epoetin alpha infusion Participation in research in the last 5 years in which any form of radioactivity was used No participation in any research trial in the last 30 days or 5 times the half-life of the used substance

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>EPO | Drug: Epoetin alpha<br>* The dosage (60.000 I/U Epoetin alpha) will be diluted in 10 ml of 0.9% sodium chloride solution and injected in a single dose intravenously in the dominant forearm (the non-dominant forearm will be used as ischemic model).<br>* Other names: Eprex;|
| Placebo Comparator: 2<br>NaCl | Drug: NaCl<br>* 0.9% sodium chloride solution as placebo dosage is 10 ml, which will be administered in the same manner as the interventional medicinal product.<br>* Other names: Sodiumchloride, saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of difference between radioactivity (quantified as counts per pixel) of the predefined area of interest of the experimental and control thenar muscle at one and four hours after reperfusion. |  | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNA polymorphisms affecting HO-1 and AMP-deaminase activity is assessed by DNA analysis. |  | 4 hours | 
| The effect of EPO treatment on heme oxygenase activity as measured in blood and as CO concentration in exhaled air. |  | 4 hours | 
| Maximal voluntary contraction and duration of the exercise during ischemia. |  | 10 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apoptosis, Annexin, Hypoxia, Ischemia-Reperfusion Injury