Ischemic Injury and Ischemic Preconditioning in Diabetes
Information source: Radboud University
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes Mellitus, Insulin-Dependent; Ischemia-Reperfusion Injury
Intervention: Ischemic preconditioning (Procedure); Forearm ischemic exercise (Procedure); Annexin A5 scintigraphy (Procedure); Diazoxide (Drug); glibenclamide (Drug); adenosine (Drug)
Phase: N/A
Status: Completed
Sponsored by: Radboud University Official(s) and/or principal investigator(s):
Richard Engbersen, MD, Study Chair, Affiliation: Radboud University Nijmegen Medical Centre; department of Pharmacology-Toxicology
Gerard Rongen, MD, PhD, Study Chair, Affiliation: Radboud University Nijmegen Medical Centre; Department of Pharmacology-Toxicology
Wim Oyen, MD, PhD, Study Chair, Affiliation: Radboud University Nijmegen Medical Centre; Department of Nuclear Medicine
Marc Mol, MD, PhD, Study Chair, Affiliation: Canisius Wilhelmina Ziekenhuis Nijmegen; Department of Internal Medicine
Paul Smits, MD, PhD, Principal Investigator, Affiliation: Radboud University Nijmegen Medical Centre; Department of Pharmacology-Toxicology
B. Bravenboer, MD, PhD, Study Chair, Affiliation: Catharina Hospital Eindhoven, Dept. of Internal Medicine
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.
Clinical Details
Official title: Acute Local Ischemic Preconditioning in Patients With Type 1 Diabetes in Vivo
Study design: Screening, Cross-Sectional, Defined Population, Prospective Study
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
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
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
Locations and Contacts
Clinical Research Centre Nijmegen; Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland 6500 HB, Netherlands
Additional Information
Starting date: June 2004
Ending date: May 2005
Last updated: April 4, 2007
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