Ischemic Injury and Ischemic Preconditioning in Diabetes

This study has been completed.
Sponsor:
Collaborator:
Dutch Diabetes Fund
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00184821
First received: September 9, 2005
Last updated: April 4, 2007
Last verified: April 2007
  Purpose

In this proof-of-concept study, forearm vulnerability to ischemic exercise is studied in patients with type 1 diabetes mellitus with and without prior ischemic preconditioning (short period of ischemia that protects against subsequent ischemic exercise). Annexin A5 scintigraphy is used to quantify subtle signs of mild and reversible forearm injury that results from ischemic exercise.

The following hypotheses are tested:

  1. Patients with type 1 diabetes are not more vulnerable to ischemic injury as compared with previously studied healthy volunteers.
  2. Ischemic preconidtioning is still present in patients with type 1 diabetes. Depending on the validity of hypothesis 2, the effect of short pharmacological interventions are studied on vulnerability to forearm ischemia/reperfusion injury in the absence or presence of local forearm ischemic preconditioning.

Condition Intervention
Diabetes Mellitus, Insulin-Dependent
Ischemia-Reperfusion Injury
Procedure: Ischemic preconditioning
Procedure: Forearm ischemic exercise
Procedure: Annexin A5 scintigraphy
Drug: Diazoxide
Drug: glibenclamide
Drug: adenosine

Study Type: Observational
Study Design: Observational Model: Defined Population
Primary Purpose: Screening
Time Perspective: Cross-Sectional
Official Title: Acute Local Ischemic Preconditioning in Patients With Type 1 Diabetes in Vivo

Resource links provided by NLM:


Further study details as provided by Radboud University:

Estimated Enrollment: 20
Study Start Date: June 2004
Study Completion Date: May 2005
Detailed Description:

All patients will be studied in supine position after an overnight fast, while plasma glucose levels are monitored. In the first 8 patients intravenous insulin is administered as needed, to reach target glucose levels between 5-7 mmol/l. Patients will be subjected to 10 minutes of forearm ischemia (non-dominant arm), combined with handgripping at 50% of maximal force until exhaustion. Upon reperfusion, Tc-99m-HYNIC-Annexin A5 will be injected intravenously. Targeting of annexin A5 to thenar muscle and forearm flexor muscle will be quantified as the percentage difference in radioactivity between experimental and control side. This procedure will be performed twice (randomized cross-over design), with at least 2 week interval, either with or without 10 minutes ischemia followed by 10 minutes of reperfusion prior to ischemic exercise.

Depending on the results of this study, substudies will be performed to study the effect of diazoxide (K-ATP channel opener, may mimic ischemic preconditioning), glibenclamide (K-ATP channel blocker, may inhibit ischemic preconditioning) or adenosine (infusion into brachial artery of non-dominant arm as a substitute for ischemic preconditioning).

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • type 1 diabetes mellitus
  • age 18-50 years

Exclusion Criteria:

  • hypertension (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg
  • cardiovascular disease (coronary artery insufficiency,CVA/TIA, peripheral artery disease
  • HbA1c > 9%
  • Body Mass Index < 25 kg/m2
  • Unable to stop co-medication (other than insulin) for 1 week
  • Previous exposure to radiation (diagnostic or therapeutic) in the past year
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00184821

Locations
Netherlands
Clinical Research Centre Nijmegen; Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Dutch Diabetes Fund
Investigators
Study Chair: Richard Engbersen, MD Radboud University Nijmegen Medical Centre; department of Pharmacology-Toxicology
Study Chair: Gerard Rongen, MD, PhD Radboud University Nijmegen Medical Centre; Department of Pharmacology-Toxicology
Study Chair: Wim Oyen, MD, PhD Radboud University Nijmegen Medical Centre; Department of Nuclear Medicine
Study Chair: Marc Mol, MD, PhD Canisius Wilhelmina Ziekenhuis Nijmegen; Department of Internal Medicine
Principal Investigator: Paul Smits, MD, PhD Radboud University Nijmegen Medical Centre; Department of Pharmacology-Toxicology
Study Chair: B. Bravenboer, MD, PhD Catharina Hospital Eindhoven, Dept. of Internal Medicine
  More Information

No publications provided by Radboud University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00184821     History of Changes
Other Study ID Numbers: QKF03-diab, 2004.11.022
Study First Received: September 9, 2005
Last Updated: April 4, 2007
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Diabetes
Ischemia
Annexin A5 scintigraphy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Ischemia
Reperfusion Injury
Autoimmune Diseases
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Pathologic Processes
Postoperative Complications
Vascular Diseases
Annexin A5
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 22, 2014