Infusion of a Single Dose of Erythropoietin to Prevent Injury in an Ischemia Reperfusion Forearm Model (IPIIR)
Primary Purpose
Ischemia-Reperfusion Injury, Myocardial Infarction
Status
Unknown status
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Epoetin alpha
NaCl
Sponsored by
About this trial
This is an interventional basic science trial for Ischemia-Reperfusion Injury focused on measuring Apoptosis, Annexin, Hypoxia, Ischemia-Reperfusion Injury
Eligibility Criteria
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
Sites / Locations
- Clinical Research Centre Nijmegen
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
EPO
NaCl
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
DNA polymorphisms affecting HO-1 and AMP-deaminase activity is assessed by DNA analysis.
The effect of EPO treatment on heme oxygenase activity as measured in blood and as CO concentration in exhaled air.
Maximal voluntary contraction and duration of the exercise during ischemia.
Full Information
NCT ID
NCT00691613
First Posted
June 3, 2008
Last Updated
March 11, 2010
Sponsor
University Medical Center Groningen
Collaborators
Radboud University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT00691613
Brief Title
Infusion of a Single Dose of Erythropoietin to Prevent Injury in an Ischemia Reperfusion Forearm Model
Acronym
IPIIR
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2010
Overall Recruitment Status
Unknown status
Study Start Date
July 2010 (undefined)
Primary Completion Date
October 2011 (Anticipated)
Study Completion Date
December 2011 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
University Medical Center Groningen
Collaborators
Radboud University Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemia-Reperfusion Injury, Myocardial Infarction
Keywords
Apoptosis, Annexin, Hypoxia, Ischemia-Reperfusion Injury
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
EPO
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
NaCl
Intervention Type
Drug
Intervention Name(s)
Epoetin alpha
Other Intervention Name(s)
Eprex
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
NaCl
Other Intervention Name(s)
Sodiumchloride, saline
Intervention Description
0.9% sodium chloride solution as placebo dosage is 10 ml, which will be administered in the same manner as the interventional medicinal product.
Primary Outcome Measure Information:
Title
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.
Time Frame
4 hours
Secondary Outcome Measure Information:
Title
DNA polymorphisms affecting HO-1 and AMP-deaminase activity is assessed by DNA analysis.
Time Frame
4 hours
Title
The effect of EPO treatment on heme oxygenase activity as measured in blood and as CO concentration in exhaled air.
Time Frame
4 hours
Title
Maximal voluntary contraction and duration of the exercise during ischemia.
Time Frame
10 minutes
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
W. T. Ruifrok, MD
Phone
+31 50 361 6161
Ext
77758
Email
w.t.ruifok@thorax.umcg.nl
First Name & Middle Initial & Last Name or Official Title & Degree
R. A. de Boer, MD, PhD
Phone
+31 50 361 6161
Ext
12355
Email
r.a.de.boer@thorax.umcg.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
W. H. van Gilst, Prof, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
P. Smits, Prof, MD, PhD
Organizational Affiliation
University Medical Centre Nijmegen
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
W. T. Ruifrok, MD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
G. A. Rongen, MD, PhD
Organizational Affiliation
University Medical Centre Nijmegen
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
D.J. van Veldhuisen, Prof, MD, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
W. Oyen, Prof, MD, PhD
Organizational Affiliation
University Medical Centre Nijmegen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
R. A. de Boer, MD, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
P.P. van Geel, MD, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
R. A. Tio, MD, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Research Centre Nijmegen
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6500 HB
Country
Netherlands
Facility Contact:
First Name & Middle Initial & Last Name & Degree
G. A. Rongen, MD, PhD
12. IPD Sharing Statement
Links:
URL
http://www.umcn.nl
Description
Webpage of the University Medical Centre Nijmegen
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Infusion of a Single Dose of Erythropoietin to Prevent Injury in an Ischemia Reperfusion Forearm Model
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