Condition category
Circulatory System
Date applied
09/03/2012
Date assigned
22/05/2012
Last edited
19/05/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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b-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and sulfonylurea drugs are withdrawn five days before the study. Nitrates are withdrawn 2 days before.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
whady.hueb@incor.usp.br

Trial website

Contact information

Type

Scientific

Primary contact

Prof Whady Hueb

ORCID ID

Contact details

Av Dr Eneas de Carvalho Aguiar
44 AB 114 Cerqueira Cesar
Sao Paulo
05403000
Brazil

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

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

Acronym

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

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

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

Condition

Type 2 diabetes / coronary artery disease

Intervention

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

Other

Phase

Not Applicable

Drug names

Primary outcome measures

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

15/01/2008

Overall trial end date

15/01/2013

Reason abandoned

Eligibility

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

Patient

Age group

Adult

Gender

Both

Target number of participants

206

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

15/01/2008

Recruitment end date

15/01/2013

Locations

Countries of recruitment

Brazil

Trial participating centre

Av Dr Eneas de Carvalho Aguiar
Sao Paulo
05403000
Brazil

Sponsor information

Organisation

Zerbini Foundation (Fundação Zerbini) (Brazil)

Sponsor details

Av Dr Eneas de Carvalho Aguiar
44 AB 114 Cerqueira Cesar
Sao Paulo
05403000
Brazil

Sponsor type

Hospital/treatment centre

Website

http://www.incor.usp.br

Funders

Funder type

Hospital/treatment centre

Funder name

Zerbini Foundation (Brazil)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23250803

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