Clinical trial NCT00691613: Infusion of a Single Dose of Erythropoietin to Prevent Injury in an Ischemia Reperfusion Forearm Model
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
Overall status: UNKNOWN
Phase: NA
Conditions: Ischemia-Reperfusion Injury
Myocardial Infarction
Keywords: Apoptosis
Annexin
Hypoxia
Ischemia-Reperfusion Injury
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
First posted: 2008-06-05
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: 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.
timeFrame: 4 hours
Secondary outcomes:
measure: DNA polymorphisms affecting HO-1 and AMP-deaminase activity is assessed by DNA analysis.
timeFrame: 4 hours
measure: The effect of EPO treatment on heme oxygenase activity as measured in blood and as CO concentration in exhaled air.
timeFrame: 4 hours
measure: Maximal voluntary contraction and duration of the exercise during ischemia.
timeFrame: 10 minutes
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Clinical Research Centre Nijmegen
state: Gelderland
Study officials:
affiliation: University Medical Center Groningen
name: W. H. van Gilst, Prof, PhD
role: STUDY_CHAIR
affiliation: University Medical Centre Nijmegen
name: P. Smits, Prof, MD, PhD
role: STUDY_CHAIR
affiliation: University Medical Center Groningen
name: W. T. Ruifrok, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Centre Nijmegen
name: G. A. Rongen, MD, PhD
role: STUDY_DIRECTOR
affiliation: University Medical Center Groningen
name: D.J. van Veldhuisen, Prof, MD, PhD
role: STUDY_DIRECTOR
affiliation: University Medical Centre Nijmegen
name: W. Oyen, Prof, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: R. A. de Boer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: P.P. van Geel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: R. A. Tio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: