Ischemic Injury and Ischemic Preconditioning in Diabetes

April 4, 2007 updated by: Radboud University Medical Center

Acute Local Ischemic Preconditioning in Patients With Type 1 Diabetes in Vivo

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Observational

Enrollment

20

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
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500 HB
        • Clinical Research Centre Nijmegen; Radboud University Nijmegen Medical Centre

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

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

Collaborators and Investigators

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

Sponsor

Radboud University Medical Center

Collaborators

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

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

June 1, 2004

Study Completion (Actual)

May 1, 2005

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (Estimate)

September 16, 2005

Study Record Updates

Last Update Posted (Estimate)

April 5, 2007

Last Update Submitted That Met QC Criteria

April 4, 2007

Last Verified

April 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • QKF03-diab
  • 2004.11.022

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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