Glucose Optimisation With Angiotensin II Antagonist Losartan (GOAAL)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Amlodipine 10 mg or Losartan 100 mg + Amlodipine 5 mg

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.

• Study Type: Interventional
• Enrollment: 25
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Insulin sensitivity assessed with hyperinsulinaemic isoglycaemic glucose clamp(GDR)

Secondary Outcome Measures

Outcome Measure
C-peptide
HOMA-IR
Heart rate variability
Catecholamines
Fasting serum glucose
Fasting serum insulin
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
Baroreflex sensitivitiy
Microalbuminuria

Collaborators and Investigators

• Sponsor: Ullevaal University Hospital
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Sverre E Kjeldsen, MD, PhD, Ullevaal University Hospital

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Study Completion: July 1, 2005

Study Registration Dates

• First Submitted: October 10, 2005
• First Submitted That Met QC Criteria: October 10, 2005
• First Posted (Estimate): October 12, 2005

Study Record Updates

• Last Update Posted (Estimate): July 6, 2011
• Last Update Submitted That Met QC Criteria: July 3, 2011
• Last Verified: October 1, 2005

More Information

Terms related to this study

• Keywords: Hypertension; Diabetes Mellitus; Insulin Resistance; Amlodipine; Losartan; Calcium Channel Blockers; Angiotensin II Type I Receptor Blockers
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Losartan
• Other Study ID Numbers: 308-1