The Effect of Rosiglitazone on Ischemia-reperfusion-injury Using Annexin A5 Scintigraphy.
Condition: Ischemia-Reperfusion Injury; The Metabolic Syndrome
MeSH terms: Reperfusion Injury; Metabolic Syndrome; Syndrome; Ischemia; Wounds and Injuries
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): rosiglitazone
Intervention type(s): Drug
Intervention description(s): Rosiglitazone 4 mg bidaily for 8 weeks
Intervention MeSH terms: Rosiglitazone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: rosiglitazone; ischemia-reperfusion injury; human; Annexin A5 scintigraphy; metabolic syndrome