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

NCT00691613 | Unknown

• 2 other identifiers: WTR-ECG-3EudraCT 2007-001089-33
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemia-Reperfusion Injury; Myocardial Infarction

Keywords

Apoptosis; Annexin; Hypoxia; Ischemia-Reperfusion Injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (2)

1

EXPERIMENTAL

EPO

Drug: Epoetin alpha

2

PLACEBO COMPARATOR

NaCl

Drug: NaCl

Interventions

Epoetin alpha DRUG

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).

Also known as: Eprex

1

NaCl DRUG

0.9% sodium chloride solution as placebo dosage is 10 ml, which will be administered in the same manner as the interventional medicinal product.

Also known as: Sodiumchloride, saline

2

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers between 18 and 40 years of age
• male
• Volunteers are not allowed smoking 24 hours before the start of the experiment

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Radboud University Medical Center: collaborator

Study Sites (1)

Clinical Research Centre Nijmegen

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Related Links

• Webpage of the University Medical Centre Nijmegen

MeSH Terms

Conditions

Reperfusion Injury; Myocardial Infarction; Hypoxia

Interventions

Epoetin Alfa; Sodium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Heart Diseases; Infarction; Ischemia; Necrosis; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• W. H. van Gilst, Prof, PhD

  University Medical Center Groningen

  STUDY CHAIR

• P. Smits, Prof, MD, PhD

  University Medical Centre Nijmegen

  STUDY CHAIR

• W. T. Ruifrok, MD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• G. A. Rongen, MD, PhD

  University Medical Centre Nijmegen

  STUDY DIRECTOR

• D.J. van Veldhuisen, Prof, MD, PhD

  University Medical Center Groningen

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

W. T. Ruifrok, MD

CONTACT

+31 50 361 6161; w.t.ruifok@thorax.umcg.nl

R. A. de Boer, MD, PhD

CONTACT

+31 50 361 6161; r.a.de.boer@thorax.umcg.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 3, 2008
• First Posted: June 5, 2008
• Study Start: July 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2011
• Last Updated: March 12, 2010

Record last verified: 2010-03

Locations

NL (1)