Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects

• Status: Terminated
• Trial end date: 2012-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Hypothesis:

The use of candesartan 16-32 mg/d for 6 months improves the carbohydrate metabolism, and decreases the plasmatic levels of adipocytokines and oxidative stress markers, in non diabetic, non hypertensive subjects with dysglycemia and abdominal obesity, and these effects are independent of the changes in arterial blood pressure.

General Objectives:

The objective is to study the impact of the treatment with candesartan in the carbohydrate metabolism and the plasmatic levels of adipocytokines and oxidative stress markers, in non diabetic, non hypertensive subjects with dysglycemia and abdominal obesity.

Study Design:

This is a randomized, double blind, cross-over, placebo-controlled, clinical trial to assess the effects of candesartan (up to 32 mg/d for 6 months), over the carbohydrate metabolism, plasma levels of adipocytokines and concentrations of oxidative stress markers in non diabetic, non hypertensive, dysglycemic and obese subjects from Colombia. The total duration of the study is 36 months.

Population:

One hundred non diabetic, dysglycemic and obese, subjects of both genders, over 18 years old, will be included. To be included subjects should have blood pressure values under 140/90 mmHg and should be receiving no antihypertensive medical treatment.

Procedures:

Subjects whom fulfill all selection criteria will be included in a run-in period of 15 days with placebo and hygiene-dietary measures (MHD) including educational, nutritional and exercise support. The patients that during this "Run in" phase have a compliance equal to or greater than 80% will be randomized to one of the two treatment groups ("Group A" receiving candesartan 16/32 mg/d for 6 months and then placebo for 6 months, or "Group B" receiving placebo during the first 6 months and then candesartan 16/32 mg/d during the last 6 months) in a 1:1 proportion by blocks of 4 subjects. Randomization will be performed by the AstraZeneca clinical department. Both groups will concurrently receive the standard treatment with MHD. Control visits will be programmed every month. Metabolic parameters, including C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, leptin, insulin, malonaldehyde and 8-isoprostanes, will be evaluated every 6 months (at the beginning and end of each treatment).

Statistical Analysis:

The analysis strategy will be performed by intention-to-treat. In a descriptive analysis, the averages and proportions will be obtained with their corresponding 95% confidence intervals for the clinically relevant variables during the baseline evaluation. In order to evaluate the differences between the groups, the Student's t test, Mann-Whitney and Fischer's exact tests will be used according to the nature of the study variables. Multiple lineal regression will be used with the purpose of comparing the treatment groups from baseline and its changes up to the 6th month of treatment.

Ethical Aspects:

The study will be conducted according to the Helsinki declaration, the good clinical practices guidelines and the Colombian legislation. Prior to entering the study, patients must sign a written informed consent that has been approved by the Institutional Ethics Committee of Fundación Cardiovascular de Colombia.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundación Cardiovascular de Colombia
• Collaborator: AstraZeneca
• Treatments: Candesartan; Candesartan cilexetil

Criteria

Inclusion Criteria:

The subjects that fulfill the following inclusion criteria will be eligible to participate in the study:

• Men and women older than 18 years of age.

• Waist perimeter > 90 cm in males or > 80 cm in females

• Have plasma glucose levels in fasting between 100 and 125 mg/dL and/or on glucose tolerance test at 2 hours > 140 mg/dL and < 200 mg/dL.

• Having a treatment compliance of over 80% at the end of the run-in phase.

• All women with childbearing potential must have a secure contraceptive method. A secure method will be considered as sterilization by surgical methods, postmenopausal condition with an age greater than 45 years and a menopausal period equal to or greater than two years. In premenopausal women, the use of two barrier contraceptive methods including 1 month after the conclusion of the active phase of study treatment.

Exclusion Criteria:

Individuals with any of the following characteristics will be excluded:

• Prior diagnosis of type 1 or 2 diabetes mellitus, chronic or acute renal insufficiency, coronary disease clinically evident (acute myocardial infarction, chest angina, myocardial revascularization) or cardiac insufficiency, or history of prior cardiovascular events (AMI, CVD, or CABG).

• Significant chronic disease (terminal stage cirrhosis or hepatic disease or cancer) that affects the survival of patients at 12 months.

• Chronic inflammatory diseases of obesity (lupus erythematosus, rheumatoid arthritis, etc.)

• Infectious acute or chronic processes of any etiology with an occurrence within the 4 weeks prior to the beginning of the study.

• Use of steroid hormones or NSAIDs 1 month prior to the beginning of the study.

• The patient is participating in a program or under treatment to lose weight during the 8 weeks prior to the study entry.

• The patient requires (for any circumstance) treatment with immunosuppressive agents.

• Has participated in a clinical trial in the 8 weeks prior to the study entry.

• At the study entry, the patient is considering the possibility of a surgical procedure during the next 12 months.

• History of severe chronic gastritis or any condition of the gastrointestinal tract that may affect the absorption and/or distribution of any drug administered orally.

• Alteration of the hepatic function tests. The maximum value for ALT or AST will be considered as > 2 times the upper normal limit.

• Triglycerides > 600 mg/dl.

• History of the use of psychoactive drugs or abuse of alcohol.

• Positive pregnancy test in the screening visit.

• Concomitant treatment with any other antihypertensive drug.

• Contraindication to receive treatment with candesartan.

• Pathological alterations of aortic or mitral cardiac valves (stenosis or insufficiency) or hypertrophic cardiomyopathy.

• Denial to sign informed consent, or any mental condition that makes the patient part of a susceptible population