Clinical trial NCT00237588: Glucose Optimisation With Angiotensin II Antagonist Losartan (GOAAL)
Official title: Glucose Optimisation With Angiotensin II Antagonist Losartan in Patients With Hypertension and Other Risk Factors for Metabolic Syndrome (GOAAL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: Angiotensin II Type I Receptor Blockers
Amlodipine
Calcium Channel Blockers
Diabetes Mellitus
Hypertension
Insulin Resistance
Losartan
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2005-10-12
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Insulin sensitivity assessed with hyperinsulinaemic isoglycaemic glucose clamp(GDR)
Secondary outcomes:
measure: Fasting serum glucose
measure: Fasting serum insulin
measure: HOMA-IR
measure: C-peptide
measure: High sensitivity C-reactive protein
measure: Lipids (Triglycerides, Total-cholesterolHDL-cholesterol, LDL-cholesterol)
measure: Adipocytokines etc.(Adiponectin, leptin, resistin, TNF-a, PAI-1 activity, ghrelin)
measure: Serum uric acid
measure: Catecholamines
measure: Baroreflex sensitivitiy
measure: Heart rate variability
measure: Microalbuminuria
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Cardiovascular and Renal Research Center/ Department of Cardiology, Ullevaal University Hospital
Study officials:
affiliation: Ullevaal University Hospital
name: Sverre E Kjeldsen, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Aksnes TA, Reims HM, Guptha S, Moan A, Os I, Kjeldsen SE. Improved insulin sensitivity with the angiotensin II-receptor blocker losartan in patients with hypertension and other cardiovascular risk factors. J Hum Hypertens. 2006 Nov;20(11):860-6. doi: 10.1038/sj.jhh.1002087. Epub 2006 Sep 21.