Ischemic Injury and Ischemic Preconditioning in Diabetes

Sponsor

Radboud University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00184821

Collaborator

Dutch Diabetes Fund (Other)

Enrollment

Location

Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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:

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 or Disease	Intervention/Treatment	Phase
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).

Study Design

Study Type:

Observational

Observational Model:

Defined Population

Time Perspective:

Other

Official Title:

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

Study Start Date :

Jun 1, 2004

Actual Study Completion Date :

May 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Centre Nijmegen; Radboud University Nijmegen Medical Centre	Nijmegen	Gelderland	Netherlands	6500 HB

Sponsors and Collaborators

Radboud University Medical Center
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