Telmisartan and Losartan in Hypertensive IGT

Hypertension Clinical Trial

Official title:

Telmisartan vs. Losartan in Hypertensive Patients With Impaired Glucose Tolerance: A Comparison of Their Antihypertensive, Metabolic, and Vascular Effects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00407862
• Other study ID #: TCW-02-04
• Status: Completed
• Phase: Phase 4
• First received: December 4, 2006
• Last updated: December 4, 2006
• Start date: January 2005
• Est. completion date: June 2006

Study information

• Verified date: December 2006
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and Women
• Study type: Interventional

Clinical Trial Summary

Inhibition of RAS delays onset of diabetes in clinical studies. Preliminary evidence suggests that telmisartan may have unique metabolic properties compared to other ARB due to activation of PPARγ.

This should be tested in comparison with an ARB that is metabolically neutral in already published studies.

H0: Telmisartan is not different from Losartan with respect to metabolic and vascular effects.

H1: Telmisartan is different from Losartan with respect to metabolic and vascular effects.

Description:

Background: Both, ACE-inhibitors as well as angiotensin-II-type-1 (AT1) receptor antagonists seem to reduce the development of type-II diabetes in patients with hypertension and/or high vascular risk (1-3). The major drawback of that evidence is that it derives from post-hoc analyses in studies with rather poor metabolic phenotypisation of the populations included. Additionally, all that evidence is based on measurements of fasting plasma glucose.

In subjects with impaired glucose tolerance (IGT), insulin resistance and dysfunction of pancreatic beta-cells (in variable contribution) have already established increased postprandial hyperglycemia with a consecutively increased cardiovascular risk (4, 5). In addition they have a considerable risk for future development of manifest type-II diabetes in the range of 3-6 % within a year (6, 7). In such patients prevention of diabetes may also result in cardiovascular prevention. As subjects with IGT often exhibit a more or less pronounced metabolic syndrome, hypertension is a frequently found comorbidity and vice versa IGT is frequent in hypertensive patients suggesting a possible common soil of the two diseases (8).

Given these evidences, hypertensive subjects with IGT are a very suitable target population to study metabolic and vascular effects of an angiotensin-II-type-1-receptor antagonist.

Finally, it has to be acknowledged that insulin resistance needs to be seen in the context of the proinflammatory changes of the metabolic syndrome, the endothelial dysfunction associated and the possibly central role of the adipocyte (Fig. 1). Within that context, the hypothesis was put forward that blockade of the angiotensin system might prevent type-II diabetes via effects on fat cells (9).

Rationale: The effects of different angiotensin-II-type-1-receptor antagonists on insulin sensitivity have been investigated in various studies with different, either positive (10) or negative (11, 12) results but no in-depht investigations into detailed metabolic and vascular effects have been performed.

Telmisartan is an angiotensin-II-type-1-receptor antagonist that very recently has been described to possess the specific properties of a partial activator of PPARγ (13). This effect is not found for other comparable compunds such as losartan. Genes of whom the expression is under control of that receptor are centrally involved into the pathology of the metabolic syndrome as outlined above and activation of that receptor results in improved insulin sensitivity, ameliorated endothelial dysfunction, reduced inflammation and potentially preserved beta-cell function (for review see (14)). Therefore, telmisartan is a candidate that might possess very specific beneficial properties in addition to its antihypertensive effects.

Objective: To compare the metabolic and vascular effects of telmisartan and metoprolol in hypertensive patients with IGT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• IGT according the criteria of the WHO

• standardised office blood pressure > 140/90 mmHG or treated hypertension

• 40 - 75 years of age

• signed informed consent

Exclusion Criteria:

• known hypersensitivity towards telmisartan or losartan

• concommitant treatment with ACE-inhibitors

• BMI > 35 kg/m2

• inability to perform self-control of blood pressure

• acute coronary syndrome or cerebrovascular event within the last 3 months

• Revascularisation within the last 3 months

• heart failure > NYHA 2

Study Design

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

Related Conditions & MeSH terms

• Glucose Intolerance
• Hypertension
• Impaired Glucose Tolerance

Intervention

Drug:
• Telmisartan 80 mg

• Losartan 50 mg

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HOMA index
Primary	ISI
Primary	FMD
Primary	Blood pressure surge in the morning