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

NCT00405015 | Completed Phase 2

• 2 other identifiers: AR49653-4EudraCT number 2006-006208-13
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ischemia-Reperfusion Injury; The Metabolic Syndrome

Keywords

rosiglitazone; ischemia-reperfusion injury; human; Annexin A5 scintigraphy; metabolic syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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.

Study Arms (2)

1

EXPERIMENTAL

Placebo first

Drug: rosiglitazone

2

EXPERIMENTAL

Rosiglitazone first

Drug: rosiglitazone

Interventions

rosiglitazone DRUG

Rosiglitazone 4 mg bidaily for 8 weeks

1; 2

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Clinical research Center Nijmegen

Nijmegen, 6500 HB, Netherlands

Location

Related Publications (4)

• Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC Jr, Sowers JR. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999 Sep 7;100(10):1134-46. doi: 10.1161/01.cir.100.10.1134. No abstract available.

  PMID: 10477542 BACKGROUND

• Aronson D, Rayfield EJ, Chesebro JH. Mechanisms determining course and outcome of diabetic patients who have had acute myocardial infarction. Ann Intern Med. 1997 Feb 15;126(4):296-306. doi: 10.7326/0003-4819-126-4-199702150-00006.

  PMID: 9036802 BACKGROUND

• Yue TL, Bao W, Gu JL, Cui J, Tao L, Ma XL, Ohlstein EH, Jucker BM. Rosiglitazone treatment in Zucker diabetic Fatty rats is associated with ameliorated cardiac insulin resistance and protection from ischemia/reperfusion-induced myocardial injury. Diabetes. 2005 Feb;54(2):554-62. doi: 10.2337/diabetes.54.2.554.

  PMID: 15677515 BACKGROUND

• Rongen GA, Oyen WJ, Ramakers BP, Riksen NP, Boerman OC, Steinmetz N, Smits P. Annexin A5 scintigraphy of forearm as a novel in vivo model of skeletal muscle preconditioning in humans. Circulation. 2005 Jan 18;111(2):173-8. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27.

  PMID: 15623546 BACKGROUND

MeSH Terms

Conditions

Reperfusion Injury; Metabolic Syndrome

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Paul Smits, MD, PhD

  Radboud University Nijmegen Medical Center, head of department of Parmacology-Toxicology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 28, 2006
• First Posted: November 29, 2006
• Study Start: April 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: October 1, 2008
• Last Updated: August 24, 2010

Record last verified: 2008-10

Locations

NL (1)