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Ischemic Injury and Ischemic Preconditioning in Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00184821
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : April 5, 2007
Dutch Diabetes Fund
Information provided by:
Radboud University

Brief Summary:

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

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).

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Study Type : Observational
Enrollment : 20 participants
Observational Model: Defined Population
Time Perspective: Other
Official Title: Acute Local Ischemic Preconditioning in Patients With Type 1 Diabetes in Vivo
Study Start Date : June 2004
Actual Study Completion Date : May 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00184821

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Clinical Research Centre Nijmegen; Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Dutch Diabetes Fund
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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
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00184821    
Other Study ID Numbers: QKF03-diab
First Posted: September 16, 2005    Key Record Dates
Last Update Posted: April 5, 2007
Last Verified: April 2007
Keywords provided by Radboud University:
Annexin A5 scintigraphy
Additional relevant MeSH terms:
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Reperfusion Injury
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Autoimmune Diseases
Immune System Diseases
Annexin A5
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Antihypertensive Agents