Glucose Optimisation With Angiotensin II Antagonist Losartan (GOAAL)

Study Overview
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Brief Summary
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To determine if angiotensin-II AT-1 receptor blockade(ARB) may improve insulin sensitivity assessed by the hyperinsulinaemic isoglycaemic glucose clamp, more than CCB therapy at a comparable dose with regards to the blood pressure-lowering effect.

Detailed Description
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Patients with hypertension have an increased prevalence of insulin resistance and an increased risk of developing diabetes mellitus with ageing. Different antihypertensive regimens have varying effects on glucose metabolism and the development of diabetes mellitus. In a double-blind,randomized cross-over study we aim to compare the metabolic effects of 10 mg amlodipine and 100 mg losartan + 5 mg amlodipine in patients with hypertension and other risk factors for the metabolic syndrome. After a 4-week open label amlodipine 5 mg run-in period, all hypertensive patient will be randomized to additional treatment with either amlodipine 5 mg or losartan 100 mg for 8 weeks. At the end of this 8-week treatment-period we will do a physical examination, laboratory-tests, hyperinsulinaemic isoglycaemic glucose clamp, heart rate variability and baroreflex sensitivity measurements. Following this is a 4-week wash-out phase where the subjects continue open label 5 mg amlodipine, before crossed over to the opposite treatment regimen for another 8 week before the final examination.

Official Title
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Glucose Optimisation With Angiotensin II Antagonist Losartan in Patients With Hypertension and Other Risk Factors for Metabolic Syndrome (GOAAL)

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Amlodipine 10 mg or Losartan 100 mg + Amlodipine 5 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Essential hypertension with diastolic blood pressure 95-110 mmHg and systolic blood pressure < 180 mmHg Previously untreated hypertension or treated with monotherapy (but not with ACE-inhibitors or Angiotensin II-receptor blockers) Impaired glucose tolerance or impaired fasting glucose (fasting plasma glucose; 6.1-7.0 mmol/l (110-126 mg/dl) Age over 18 Informed consent Any one of these: Microalbuminuria (urin excretion >20 microg/min), dyslipidemia (HDL-cholesterol <0.9 mmol/l(35 mg/dl), Triglycerides > 1.7 mmol/l (150 mg/dl), waist to hip-ratio >0.9 in men and >0.85 in women, BMI >28 kg/m2. Exclusion Criteria: Previous or current use of ACE-inhibitors or Angiotensin II-receptor blockers Previous or current antidiabetic medications Brittle pre-diabetes where the investigator anticipates pharmacological treatment within next 6 months Hypertensive patients where the investigator anticipates polytherapy within next 6 months Female patient who is pregnant or nursing or planning pregnancy within the duration of the study

Ages Eligible for Study
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Minimum Age: 18 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Amlodipine 10 mg or Losartan 100 mg + Amlodipine 5 mg|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity assessed with hyperinsulinaemic isoglycaemic glucose clamp(GDR) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting serum glucose |  |  | 
| Fasting serum insulin |  |  | 
| HOMA-IR |  |  | 
| C-peptide |  |  | 
| High sensitivity C-reactive protein |  |  | 
| Lipids (Triglycerides, Total-cholesterolHDL-cholesterol, LDL-cholesterol) |  |  | 
| Adipocytokines etc.(Adiponectin, leptin, resistin, TNF-a, PAI-1 activity, ghrelin) |  |  | 
| Serum uric acid |  |  | 
| Catecholamines |  |  | 
| Baroreflex sensitivitiy |  |  | 
| Heart rate variability |  |  | 
| Microalbuminuria |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angiotensin II Type I Receptor Blockers, Amlodipine, Calcium Channel Blockers, Diabetes Mellitus, Hypertension, Insulin Resistance, Losartan