Glucose Optimisation With Angiotensin II Antagonist Losartan (GOAAL)

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00237588
• Other study ID #: 308-1
• Status: Completed
• Phase: Phase 4
• First received: October 10, 2005
• Last updated: July 3, 2011
• Start date: December 2004
• Est. completion date: July 2005

Study information

• Verified date: October 2005
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: July 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Amlodipine 10 mg or Losartan 100 mg + Amlodipine 5 mg

Locations

Country	Name	City	State
Norway	Cardiovascular and Renal Research Center/ Department of Cardiology, Ullevaal University Hospital	Oslo

Sponsors (2)

Lead Sponsor	Collaborator
Ullevaal University Hospital	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Norway, 

References & Publications (1)

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. Epub 2006 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity assessed with hyperinsulinaemic isoglycaemic glucose clamp(GDR)
Secondary	Fasting serum glucose
Secondary	Fasting serum insulin
Secondary	HOMA-IR
Secondary	C-peptide
Secondary	High sensitivity C-reactive protein
Secondary	Lipids (Triglycerides, Total-cholesterolHDL-cholesterol, LDL-cholesterol)
Secondary	Adipocytokines etc.(Adiponectin, leptin, resistin, TNF-a, PAI-1 activity, ghrelin)
Secondary	Serum uric acid
Secondary	Catecholamines
Secondary	Baroreflex sensitivitiy
Secondary	Heart rate variability
Secondary	Microalbuminuria