Glucose Optimisation With Angiotensin II Antagonist Losartan (GOAAL)

Condition(s) targeted: Hypertension

Intervention: Amlodipine 10 mg or Losartan 100 mg + Amlodipine 5 mg (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Ullevaal University Hospital

Official(s) and/or principal investigator(s):
Sverre E Kjeldsen, MD, PhD, Study Director, Affiliation: Ullevaal University Hospital

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.

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

Study design: Educational/Counseling/Training, Randomized, Double-Blind, Active Control, Crossover Assignment, Efficacy Study

Primary outcome: Insulin sensitivity assessed with hyperinsulinaemic isoglycaemic glucose clamp(GDR)

Secondary outcome:

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

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Cardiovascular and Renal Research Center/ Department of Cardiology, Ullevaal University Hospital, Oslo 0407, Norway

Homepage for Cardiovascular and Renal Research Center, Ullevaal University Hospital, Oslo, Norway

Homepage for Cardiovascular and Renal Research Center, Ullevaal University Hospital, Oslo, Norway

Starting date: December 2004
Ending date: July 2005
Last updated: November 2, 2006