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Ischemic Injury and Ischemic Preconditioning in Diabetes

NCT ID: NCT00184821

Last Updated: 2007-04-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

20 participants

Study Classification

OBSERVATIONAL

Study Start Date

2004-06-30

Study Completion Date

2005-05-31

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Diabetes Mellitus, Insulin-Dependent Ischemia-Reperfusion Injury

Study Design

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Observational Model Type

DEFINED_POPULATION

Study Time Perspective

OTHER

Interventions

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Ischemic preconditioning

Intervention Type PROCEDURE

Forearm ischemic exercise

Intervention Type PROCEDURE

Annexin A5 scintigraphy

Intervention Type PROCEDURE

Diazoxide

Intervention Type DRUG

glibenclamide

Intervention Type DRUG

adenosine

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dutch Diabetes Fund

UNKNOWN

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Principal Investigators

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Richard Engbersen, MD

Role: STUDY_CHAIR

Radboud University Nijmegen Medical Centre; department of Pharmacology-Toxicology

Gerard Rongen, MD, PhD

Role: STUDY_CHAIR

Radboud University Nijmegen Medical Centre; Department of Pharmacology-Toxicology

Wim Oyen, MD, PhD

Role: STUDY_CHAIR

Radboud University Nijmegen Medical Centre; Department of Nuclear Medicine

Marc Mol, MD, PhD

Role: STUDY_CHAIR

Canisius Wilhelmina Ziekenhuis Nijmegen; Department of Internal Medicine

Paul Smits, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Nijmegen Medical Centre; Department of Pharmacology-Toxicology

B. Bravenboer, MD, PhD

Role: STUDY_CHAIR

Catharina Hospital Eindhoven, Dept. of Internal Medicine

Locations

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Clinical Research Centre Nijmegen; Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Netherlands

References

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Engbersen R, Riksen NP, Mol MJ, Bravenboer B, Boerman OC, Meijer P, Oyen WJ, Tack C, Rongen GA, Smits P. Improved resistance to ischemia and reperfusion, but impaired protection by ischemic preconditioning in patients with type 1 diabetes mellitus: a pilot study. Cardiovasc Diabetol. 2012 Oct 10;11:124. doi: 10.1186/1475-2840-11-124.

Reference Type DERIVED
PMID: 23051145 (View on PubMed)

Other Identifiers

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2004.11.022

Identifier Type: -

Identifier Source: secondary_id

QKF03-diab

Identifier Type: -

Identifier Source: org_study_id