The Effect of Rosiglitazone on Ischemia-reperfusion-injury Using Annexin A5 Scintigraphy.

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00405015
First received: November 28, 2006
Last updated: August 23, 2010
Last verified: October 2008
  Purpose

Cardiovascular disease is the leading cause of death in diabetic patients due to both a high event rate and a worse outcome. A pharmacological intervention that reduces ischemia-reperfusion-injury would improve the outcome of diabetic patients after a cardiovascular event. In the present study, we will use annexinA5 scintigraphy to address the following hypothesis:

Rosiglitazone reduces ischemia-reperfusion-injury in humans with insulin resistance.


Condition Intervention Phase
Ischemia-Reperfusion Injury
The Metabolic Syndrome
Drug: rosiglitazone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effect of Rosiglitazone on Ischemia-reperfusion-injury Using Annexin A5 Scintigraphy. A Double Blind Placebo- Controlled Cross-over Study in Subjects With the Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Annexin targeting in the thenar muscle after ischemic exercise. The primary analysis is the difference in annexin targeting following 8 weeks of treatment with rosiglitazone 4 mg bd or placebo.

Secondary Outcome Measures:
  • The effect of rosiglitazone as compared to placebo on the HOMA-index.
  • Changes in vital signs, body weight, clinical laboratory parameters and adverse events monitoring during the study.

Enrollment: 13
Study Start Date: April 2007
Study Completion Date: October 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Placebo first
Drug: rosiglitazone
Rosiglitazone 4 mg bidaily for 8 weeks
Experimental: 2
Rosiglitazone first
Drug: rosiglitazone
Rosiglitazone 4 mg bidaily for 8 weeks

Detailed Description:

Rationale: Cardiovascular disease is the leading cause of death in diabetic patients due to both a high event rate and a worse outcome. A pharmacological intervention that reduces ischemia-reperfusion-injury would improve the outcome of diabetic patients after a cardiovascular event. The thiazolidinedione derivatives are peroxisome proliferator-activated receptor-γ (PPARγ) ligands that are approved for the treatment of hyperglycemia in type 2 diabetes mellitus. Animal data suggest that PPARγ ligands can protect against ischemia-reperfusion-injury by improving insulin responsiveness. However, no human data on these beneficial effects are available. Recently, our group developed a human in vivo model to quantify ischemia-reperfusion-injury. In this model annexin A5 scintigraphy is used to visualize early and reversible cellular membrane changes that occur in the forearm skeletal muscle vascular bed after ischemic exercise. In the present study, we will use this approach to address the following hypothesis: Rosiglitazone reduces ischemia-reperfusion-injury in humans with insulin resistance, selected by using the criteria for the metabolic syndrome.

Study design: This is a single-center randomized, double blind, placebo-controlled crossover study with a washout period of 6 weeks.

Study population: Men and postmenopausal women, age 20-70 years with the metabolic syndrome.

Intervention: Every subject uses during 8 weeks rosiglitazone 4 mg bd and placebo bd. Week 8 and 22: assessment of ischemic-reperfusion injury with Technetium Annexin A5 Scintigraphy. Ischemic intervention: 10 minutes ischemia of the non-dominant arm with at the same time rhythmic contractions of the forearm and hand muscles.

Main study parameters/endpoints: Annexin targeting in the thenar muscle after ischemic exercise. The primary analysis is the difference in annexin targeting following 8 weeks of treatment with rosiglitazone 4 mg bd or placebo.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 3 features of the metabolic syndrome (AHA/NHLBI).
  • Willing and able to provide a signed and dated written informed consent.
  • Men or postmenopausal women aged between 20 and 70 years.

Exclusion Criteria:

  • Fasting glucose > 7,0 mmol/L or the use of hypoglycaemic agents. If fasting plasma glucose is between 6.1 and 7,0 mmol/L, an oral 75 g glucose test will be performed to exclude diabetes mellitus.
  • Exposure to a PPAR-g agonist during the last 4 months or a documented significant hypersensitivity to a PPAR-g agonist.
  • Participant in another study.
  • Angina or heart failure (NYHA I-IV).
  • Clinically significant liver disease (3 times the upper normal limit of ALAT, ASAT, AF, γGT or LDH)
  • Clinically significant anemia (male Hb < 6,9 mmol/L, female < 6,25 mmol/L)
  • Creatinin clearance < 40 mL/min
  • Alcohol or drug abuse.
  • Any physical inability to perform the exercise protocol.
  • Administration of any radio pharmacon for research purposes in the previous 5 years.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00405015

Locations
Netherlands
Clinical research Center Nijmegen
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
GlaxoSmithKline
Investigators
Principal Investigator: Gerard A Rongen, MD, PhD Radboud University Nijmegen Medical Center, department pharmacology-Toxicology
Principal Investigator: Alexander JM Rennings, MD Radboud University Nijmegen Medical Center, department of pharmacology-Toxicology
Study Director: Paul Smits, MD, PhD Radboud University Nijmegen Medical Center, head of department of Parmacology-Toxicology
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00405015     History of Changes
Other Study ID Numbers: AR49653-4, EudraCT number 2006-006208-13
Study First Received: November 28, 2006
Last Updated: August 23, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
rosiglitazone
ischemia-reperfusion injury
human
Annexin A5 scintigraphy
metabolic syndrome

Additional relevant MeSH terms:
Ischemia
Metabolic Syndrome X
Reperfusion Injury
Syndrome
Cardiovascular Diseases
Disease
Glucose Metabolism Disorders
Hyperinsulinism
Insulin Resistance
Metabolic Diseases
Pathologic Processes
Postoperative Complications
Vascular Diseases
Annexin A5
Rosiglitazone
Enzyme Inhibitors
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014