A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients

Study Overview
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Brief Summary
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The epidemic of obesity is associated with a considerable rise in the incidence of the metabolic syndrome, type 2 diabetes mellitus, and hypertension. Insulin resistance plays an important role in the pathogenesis of obesity related hypertension. These patients are at high risk to suffer from cardiovascular events. However, current guidelines for treatment of hypertension do not provide specific recommendation for the pharmacotherapy of obese hypertensive patients due to lack of prospective randomized intervention studies in non-diabetic obese hypertensive patients. Aside from their antihypertensive effects, angiotensin II receptor blockers (ARB) were shown to improve insulin sensitivity. Furthermore, metformin is commonly used to treat the obese type 2 diabetes mellitus. Metformin can also lower body weight and increase insulin sensitivity. In a prospective, double-blind, double-dummy, randomized, parallel-group study, we will evaluate the effects of ARB (telmisartan and candesartan) or amlodipine combination with metformin on weight gain, visceral fat, and metabolic parameters in obese hypertensive patients without diabetes mellitus compared with obese hypertensives on ARB or amlodipine treatment alone. This study will help to develop future comprehensive treatment strategies and guidelines for obesity related hypertension.

Official Title
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Which is the Best Treatment for Non-diabetic Hypertension With Obesity: Telmisartan, Amlodipine or Candesartan, Alone or Plus MEtformin? (HOT-ACME 1)

Conditions
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Hypertension, Obesity

Intervention / Treatment
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* Drug: Telmisartan plus Metformin
* Drug: Telmisartan
* Drug: Candesartan
* Drug: Candesartan plus Metformin
* Drug: Amlodipine
* Drug: Amlodipine plus Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Grade 1 or 2 hypertension: 140mmHg≤SBP<180mmHg, and/or 90mmHg≤DBP<110mmHg Waist circumference higher than 90cm in men, 80cm in women Exclusion Criteria: Diabetes Grade 3 hypertension: SBP≥180mmHg, or DBP≥110mmHg known allergy or hypersensitivity to trial drugs Myocardial infarction or cerebrovascular accident in the year preceding the trial Clinical Congestive Heart Failure History of hepatitis or cirrhosis History of kidney disease

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group T<br>Telmisartan | Drug: Telmisartan<br>* Telmisartan 80mg 1/d<br>* Other names: Telmisartan Alone;|
| Experimental: Group T+M<br>Telmisartan plus Metformin | Drug: Telmisartan plus Metformin<br>* Telmisartan 80mg 1/d, Metformin 250mg 2/d<br>|
| Experimental: Group C<br>Candesartan | Drug: Candesartan<br>* Candesartan 8mg daily<br>* Other names: Candesartan Alone;|
| Experimental: Group C+M<br>Candesartan pus Metformin | Drug: Candesartan plus Metformin<br>* Candesartan 8mg 1/d Metformin 250mg 2/d<br>|
| Active Comparator: Group A<br>Amlodipine | Drug: Amlodipine<br>* Amlodipine 5mg 1/d<br>* Other names: Amlodipine alone;|
| Experimental: Group A+M<br>Amlodipine plus Metformin | Drug: Amlodipine plus Metformin<br>* Amlodipine 5mg 1/d, Metformin 250mg 2/d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure |  | Baseline, 24 weeks(End of trial) | 
| Metabolic profiles, including lipid profile and blood glucose |  | Baseline, 24 weeks(End of trial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abdominal fat assessed by CT |  | Baseline, 24 weeks(End of trial) | 
| Obesity parameters, including waist circumference (WC) and body mass index (BMI) |  | Baseline, 24 weeks(End of trial) | 
| Insulin resistance assessed by fasting serum insulin and HOMA-IR |  | Baseline, 24 weeks(End of trial) | 
| Incidents of side effects between groups |  | Baseline, 24 weeks(End of trial) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Abdominal obesity, Treatment