Ischemic Injury and Ischemic Preconditioning in Diabetes
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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:
- Patients with type 1 diabetes are not more vulnerable to ischemic injury as compared with previously studied healthy volunteers.
- 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 Time Perspective: Prospective |
| Official Title: | Acute Local Ischemic Preconditioning in Patients With Type 1 Diabetes in Vivo |
| Estimated Enrollment: | 20 |
| Study Start Date: | June 2004 |
| Study Completion Date: | May 2005 |
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 |
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| Netherlands | |
| Clinical Research Centre Nijmegen; Radboud University Nijmegen Medical Centre | |
| Nijmegen, Gelderland, Netherlands, 6500 HB | |
| 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 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases Pathologic Processes Vascular Diseases Cardiovascular Diseases Postoperative Complications Adenosine Diazoxide |
Glyburide Annexin A5 Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Anti-Arrhythmia Agents Cardiovascular Agents Vasodilator Agents Antihypertensive Agents Hypoglycemic Agents Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 21, 2013