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

August 23, 2010 updated by: Radboud University Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Nijmegen, Netherlands, 6500 HB
        • Clinical research Center Nijmegen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

October 1, 2008

Study Registration Dates

First Submitted

November 28, 2006

First Submitted That Met QC Criteria

November 28, 2006

First Posted (Estimate)

November 29, 2006

Study Record Updates

Last Update Posted (Estimate)

August 24, 2010

Last Update Submitted That Met QC Criteria

August 23, 2010

Last Verified

October 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AR49653-4
  • EudraCT number 2006-006208-13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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