Effect of hypoglycemic agents on ischemic preconditioning in patients with diabetes and symptomatic coronary artery disease
| ISRCTN | ISRCTN62282580 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN62282580 |
| Secondary identifying numbers | N/A |
- Submission date
- 09/03/2012
- Registration date
- 22/05/2012
- Last edited
- 19/05/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
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b-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and sulfonylurea drugs are withdrawn five days before the study. Nitrates are withdrawn 2 days before.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
Contact information
Scientific
Av Dr Eneas de Carvalho Aguiar
44 AB 114 Cerqueira Cesar
Sao Paulo
05403000
Brazil
Study information
| Study design | Single-centre prospective study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Effect of hypoglycemic agents on ischemic preconditioning in patients with diabetes and symptomatic coronary artery disease |
| Study objectives | 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(s) | Institutional Review Board, Committee for the Analysis of Research Projects [Comissão para Análise de Projetos de Pesquisa, 07 December 2007 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 15/01/2008 |
| Completion date | 15/01/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 206 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 15/01/2008 |
| Date of final enrolment | 15/01/2013 |
Locations
Countries of recruitment
- Brazil
Study participating centre
05403000
Brazil
Sponsor information
Hospital/treatment centre
Av Dr Eneas de Carvalho Aguiar
44 AB 114 Cerqueira Cesar
Sao Paulo
05403000
Brazil
| Website | http://www.incor.usp.br |
|---|---|
"ROR" |
https://ror.org/003c2h870 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/06/2013 | Yes | No |
Editorial Notes
19/05/2017: Plain English summary added
