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

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

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.

Study Overview

• Status: Unknown
• Conditions: Myocardial Infarction; Ischemia-Reperfusion Injury
• Intervention / Treatment: Drug: Epoetin alpha; Drug: NaCl

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: W. T. Ruifrok, MD; Phone Number: 77758 +31 50 361 6161; Email: w.t.ruifok@thorax.umcg.nl
• Study Contact Backup: Name: R. A. de Boer, MD, PhD; Phone Number: 12355 +31 50 361 6161; Email: r.a.de.boer@thorax.umcg.nl

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500 HB
      • Clinical Research Centre Nijmegen
      • Principal Investigator: G. A. Rongen, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; NaCl	Drug: NaCl; 0.9% sodium chloride solution as placebo dosage is 10 ml, which will be administered in the same manner as the interventional medicinal product.; Other Names: Sodiumchloride, saline
Experimental: 1; EPO	Drug: Epoetin alpha; 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).; Other Names: Eprex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Radboud University Medical Center
• Investigators: Principal Investigator: W. T. Ruifrok, MD, University Medical Center Groningen; Study Chair: W. H. van Gilst, Prof, PhD, University Medical Center Groningen; Study Chair: P. Smits, Prof, MD, PhD, University Medical Centre Nijmegen; Study Director: G. A. Rongen, MD, PhD, University Medical Centre Nijmegen; Study Director: D.J. van Veldhuisen, Prof, MD, PhD, University Medical Center Groningen; Principal Investigator: W. Oyen, Prof, MD, PhD, University Medical Centre Nijmegen; Principal Investigator: R. A. de Boer, MD, PhD, University Medical Center Groningen; Principal Investigator: P.P. van Geel, MD, PhD, University Medical Center Groningen; Principal Investigator: R. A. Tio, MD, PhD, University Medical Center Groningen

Publications and helpful links

Helpful Links

• Webpage of the University Medical Centre Groningen
• Webpage of the University Medical Centre Nijmegen

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Anticipated): October 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: June 3, 2008
• First Submitted That Met QC Criteria: June 3, 2008
• First Posted (Estimate): June 5, 2008

Study Record Updates

• Last Update Posted (Estimate): March 12, 2010
• Last Update Submitted That Met QC Criteria: March 11, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Hypoxia; Apoptosis; Annexin; Ischemia-Reperfusion Injury
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Myocardial Infarction; Infarction; Ischemia; Wounds and Injuries; Reperfusion Injury; Hematinics; Epoetin Alfa
• Other Study ID Numbers: WTR-ECG-3; EudraCT 2007-001089-33