Condition category
Circulatory System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Background and aims:
A myocardial ischemia occurs when the blood flow to your heart is reduced, preventing it from receiving enough oxygen. Ischemic preconditioning (IPC) is an experimental technique that promotes resistance to ischemic insult. It seems that the underlying mechanism for this phenomenon involve the KATP (potassium ATP) channels. Some hypoglycemic (low bloof sugar) drugs, like glybenclamide, can eliminate this protective effect, contributing to a worse prognosis. The aim of this study is to evaluate the effects of 2 hypoglycemic agents on myocardial IPC in patients with type 2 diabetes and multivessel coronary disease.

Who can participate?
Patients with type 2 diabetes and multi-vessel coronary disease confirmed by coronary angiography and ischemic exercise test.

What does the study involve?
The study involves two phases. In phase one, (without medication), all participants undergo two consecutive treadmill exercise tests (ET1 and ET2) to demonstrate IPC. After that all patients will receive hypoglycemic drugs for one week and they will undergo to more two sequential ET (ET3 and ET4), in phase II. The time interval between the ET1-2 and ET3-4 will be 30 minutes. Calcium entry blocking agents, b-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and sulfonylurea drugs are withdrawn five days before the study. Nitrates are withdrawn 2 days before.

What are the possible benefits and risks of participating?
Preserving the viability of myocardium therefore has been recognized as a major therapeutic target. Classes of pharmacological agents that may be able to mimic or preserve the protection conferred by ischemic preconditioning provide some basis for a possible clinically improvement in patients with coronary artery disease. All patients selected are stable clinically and not demonstrate any potential risk. The participants will receive an individualized follow-up program consisting of specialized medical care in Heart Institute, University of Sao Paulo.

Where is the study run from?
Heart Institute, University of Sao Paulo (Brazil)

When is study starting and how long is it expected to run for?
January 2008 to January 2013

Who is funding the study?
Zerbini Foundation

Who is the main contact?
Dr Whady Hueb

Trial website

Contact information



Primary contact

Prof Whady Hueb


Contact details

Av Dr Eneas de Carvalho Aguiar
44 AB 114 Cerqueira Cesar
Sao Paulo

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Effect of hypoglycemic agents on ischemic preconditioning in patients with diabetes and symptomatic coronary artery disease


Study hypothesis

We hypothesized that both glinide and inhibitor of dipeptidyl peptidase-4 (DPP-4) drugs may interfere with ischemic preconditioning cellular mechanism. For this reason we will test this hypothesis by conducting a prospective study in which individuals with type 2 diabetes and symptomatic coronary artery disease were selected to receive glinide or inhibitor of DPP-4 and we will evaluate their effects on warm-up phenomenon.

Ethics approval

Institutional Review Board, Committee for the Analysis of Research Projects [Comissão para Análise de Projetos de Pesquisa, 07 December 2007

Study design

Single-centre prospective study

Primary study design


Secondary study design

Non randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Type 2 diabetes / coronary artery disease


Meglitinide group: Repaglinide 6 mg daily, oral dose, during 1 week
Inhibitor DPP-4 group: Vildagliptin 100 mg daily, oral dose, during 1 week

Intervention type



Not Applicable

Drug names

Primary outcome measure

We will evaluate the effect of two hypoglycemic drugs on ischemic preconditioning by two sequential treadmill exercise tests (warm-up phenomenon). The warm-up phenomenon will be analysed by following parameters:
1. The time to onset of 1.0-mm ST-segment depression (the horizontal or downsloping ST-segment depressions were considered)
2. Rate pressure product (heart rate x systolic blood pressure) at the onset of 1.0-mm ST-segment depression

Secondary outcome measures

No secondary outcome measures

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Patients with type 2 diabetes mellitus under adequate drug treatment and no insulin dependence
2. A positive test for myocardial ischemia during a previous treadmill exercise test (horizontal or downsloping ST-segment depression >=1.0 mm)
3. Multivessel coronary disease confirmed by coronary angiography, and coronary disease with an internal diameter reduction of >=70% of at least two major coronary branches
4. Preserved left ventricular function confirmed by transthoracic echodopplercardiography

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Myocardial infarction during the last 3 month
2. Severely impaired myocardial function (ejection fraction <45%)
3. ECG changes that could interfere with the interpretation of the ST segment
4. Impaired hepatic or renal function
5. Progressive fatal disease
6. Mental disorder

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Av Dr Eneas de Carvalho Aguiar
Sao Paulo

Sponsor information


Zerbini Foundation (Fundação Zerbini) (Brazil)

Sponsor details

Av Dr Eneas de Carvalho Aguiar
44 AB 114 Cerqueira Cesar
Sao Paulo

Sponsor type

Hospital/treatment centre



Funder type

Hospital/treatment centre

Funder name

Zerbini Foundation (Brazil)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2013 results in:

Publication citations

  1. Results

    Rahmi RM, Uchida AH, Rezende PC, Lima EG, Garzillo CL, Favarato D, Strunz CM, Takiuti M, Girardi P, Hueb W, Kalil Filho R, Ramires JA, Effect of hypoglycemic agents on ischemic preconditioning in patients with type 2 diabetes and symptomatic coronary artery disease., Diabetes Care, 2013, 36, 6, 1654-1659, doi: 10.2337/dc12-1495.

Additional files

Editorial Notes

19/05/2017: Plain English summary added