Effects of Vildagliptin Versus Glibenclamide on Glycemia After Exercise in Patients With Type 2 Diabetes

NCT ID: NCT01867502

Last Updated: 2014-05-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2015-08-31

Brief Summary

Exercise is considered a way to benefit the health of unhealthy and healthy individuals. This is confirmed by different scientific researches, in which people who participated improve their health. The present study will be conducted to test the hypothesis that vildagliptin associated with metformin may have more impact in improving glucose variability after a sub-maximal exercise test, as compared to glibenclamide. Our general aim will be to evaluate glucose variability after the submaximal exercise test under the treatment with vildagliptin or glibenclamide. The specific aims of this study are to evaluate the oxidative stress, endothelial function, metabolic and cardiovascular responses to exercise under the treatment with vildagliptin or glibenclamide. All these responses are important in patients with Diabetes Mellitus type II. Allied to the patient's routine treatment (metformin), they will receive orally a second drug, to take in 12 weeks. The patients will be raffled to take one of the two drugs that act on glycemia, that are called vildagliptin (50 mg of this drug twice a day) and glibenclamide (5 mg once a day during the first week and later you will increase to 5 mg twice a day). The metformin drug will continue be used.

Patients who meet the eligible criteria for the study will first make the test of the maximum effort, to determination of peak oxygen consumption (VO2peak) and ventilatory thresholds. Forty eight hours after this test, patients will be allowed to do the pre-drugs protocol that will be given in three consecutive days as explained below.

• Day 1: Begin a 24-hour urinary collection, perform vascular doppler ultrasound to evaluate endothelial function and then the glucose sensor will be inserted subcutaneously (begin continuous glucose monitoring system - CGMS evaluation);
• Day 2: End the 24-hour urinary collection, submit to the submaximal test (blood collection at baseline, 15 and 30 min of the session, and 60 min after recovery). On the same day, the patients will begin 24h ambulatory blood pressure monitoring (24h-ABPM).
• Day 3: Removal of the glucose sensor; end of the 24h ABPM, randomization. This same protocol, except the randomization will be repeated at the end of the 12 week treatment.

Detailed Description

The main procedures will occur during three consecutive days, before randomization and 3 days before 12 weeks. In the first day, the patients will begin the 24hour urinary collection; the ultrasonography will be made in fasting state and they will place the sensors (CGMS and MAPA). In the second day, the blood samples will be collected and the patients will undergo sub-maximal exercise test; in the third day the sensors will be removed. The sub-maximal exercise test will occur on day 2 after a standard breakfast (500 kcal; 60% carbohydrate, 30% fat and 10% protein) after 8 hours overnight fast. After the three days of the first assessments, the selected patients will be divided into two groups, the group 1 receiving vildagliptin and the group 2 receiving glibenclamide for 12 weeks. There will be follow up visits on week 4 and 8. The variables in response to exercise (sub-maximal test) will be compared between the groups after 12 weeks.

The sample estimated will be 20 patients (10% drop out included) with DM2, from outpatient clinics of Serviço de Endocrinologia do Hospital de Clínicas de Porto Alegre (HCPA) or from public health. Patients will be randomized to metformin plus vildagliptin (MET + vilda), which will receive an additional vidagliptin dose of 50 mg twice a day and metformin plus glibenclamide group (MET + gliben) that will receive an additional glibenclamide dose of 5 - 20 mg once a day. Based on Marfella et al (13) study on the evaluation of the efficacy of treatment with Vildagliptin or Sitagliptin on blood glucose in patients with DM2 inadequately controlled with Metformin, a sample size with a 90% power and one alpha (α) of 0, 01 was calculated. Vidagliptin had a serious effect (51% reduction in MAGE), since the average difference was 25mg/dl with a 16 and 7mg/dl SD. After 20 subjects were analyzed, the calculated sample will be redone for confirming the sample efficacy for evidence of the expected effect evidence.

Adverse events, including serious adverse events or pregnancies will be collected and reported in the medical report of the study (Annex IV).

The reports containing serious adverse events or pregnancies will be forwarded to the respective manufacturer laboratory within 24 hrs after their knowledge, and the health authority according to the local law.

Conditions

Diabetes Mellitus, Type 2; Hypoglycemic Agents; Diabetic Blood Glucose Monitoring; Exercise

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MET + Glibenclamide Group

Usual Metformin stipulated: 500 or 850mg 3 times a day, if tolerated by patients.

The initial dose of glibenclamide group will be 5mg / day during the first week of study, later it will increase to 10 mg / day (2 x 5mg). When the adjustments will be done, the dose may reaching the maximum dose allowed, which is 20 mg / day.

Group Type: OTHER

MET + Glibenclamide Group

Intervention Type: DRUG

The initial dose of glibenclamide group will be 5mg / day during the first week of study, later it will increase to 10 mg / day (2 x 5mg). With the control the dose may be adjusted, reaching the maximum dose allowed, which is 20 mg / day.

For the glycemic control evaluation will be used the capillar glycemia at home. The adjustments will be done by the researcher coordinator.

MET + Vildagliptin Group

Usual Metformin stipulated: 500 or 850mg 3 times a day, if tolerated by patients.

Vidagliptin group will receive 50mg of this drug twice a day during 12 weeks.

Group Type: OTHER

MET + Vildagliptin Group

Intervention Type: DRUG

Vidagliptin group will receive 50mg of this drug twice a day during 12 weeks added to usual metformin.

For the glicemic control evaluation will be used the capilar glycemia at home. The adjustments will be done by the researcher coordinator.

Interventions

MET + Vildagliptin Group

Vidagliptin group will receive 50mg of this drug twice a day during 12 weeks added to usual metformin.

For the glicemic control evaluation will be used the capilar glycemia at home. The adjustments will be done by the researcher coordinator.

Intervention Type: DRUG

MET + Glibenclamide Group

The initial dose of glibenclamide group will be 5mg / day during the first week of study, later it will increase to 10 mg / day (2 x 5mg). With the control the dose may be adjusted, reaching the maximum dose allowed, which is 20 mg / day.

For the glycemic control evaluation will be used the capillar glycemia at home. The adjustments will be done by the researcher coordinator.

Intervention Type: DRUG

Other Intervention Names

Galvus®; Glyburide; Glucophage; Daonil®; Glucophage

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetes (fasting glucose ≥ 126 mg/dl or 7.0 mmol/l)(25);
• Recent HbA1C determination (between 7, 5 and 10%);
• Not involved in regular physical exercise;
• Older than 18 years;
• In use of Metformin.

Exclusion Criteria

• Smoker and use of analgesic or anti-inflammatory drugs during the week of the study
• BMI > 40 kg/m²;
• Proliferative retinopathy;
• Ischemic cardiomyopathy;
• Peripheral vascular disease;
• Blood Aspartate transaminase (AST) and Alanine transaminase (ALT) 2.5 times higher the normal concentration before screening visit
• Lactose intolerance;
• Renal insufficiency (creatinine clearance <60ml/min);
• Blood pressure more than 180/100mmHg at rest (3 consecutive measures).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Beatriz BS Schaan, PhD

Role: PRINCIPAL_INVESTIGATOR

Federal University of Rio Grande do Sul

Aline AF Fofonka, MSc

Role: STUDY_CHAIR

Federal University of Rio Grande do Sul

Locations

Hospital de Clínicas de Porto Alegre Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Aline AF Fofonka, MSc

Role: CONTACT

alinefofonka@hotmail.com

55-5192339191

Beatriz BS Schaan, PhD

Role: CONTACT

breatizschaan@gmail.com

5551-33598127

Facility Contacts

Aline Fofonka, MSc

Role: primary

alinefofonka@hotmail.com

55-5192339191

References

Fofonka A, Ribeiro JP, Casali KR, Schaan BD. Effects of vildagliptin compared with glibenclamide on glucose variability after a submaximal exercise test in patients with type 2 diabetes: study protocol for a randomized controlled trial, DIABEX VILDA. Trials. 2014 Nov 4;15:424. doi: 10.1186/1745-6215-15-424.

Reference Type: DERIVED

PMID: 25366037 (View on PubMed)

Other Identifiers

12-0444

Identifier Type: OTHER

Identifier Source: secondary_id

CLAF237ABR05T

Identifier Type: -

Identifier Source: org_study_id