Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
The primary objective is to evaluate the effect of 9 weeks treatment with either telmisartan or ramipril on NO bioavailability in the renal vasculature, measured as renal plasma flow (RPF) in response to NG-monomethyl-L-arginine (LNMMA) infusion.

Detailed Description
-----------------
This study was designed as a randomised, double-blind, double-dummy, parallel group in hypertensive patients with type 2 diabetes and normo- or microalbuminuria over a treatment period of 9 weeks. After a 4 week Run-in period, patients will be randomised to one of the treatment groups and receive either Telmisartan 40 - 80 mg or Ramipril 5 - 10 mg. The treatment regimen is a forced titration with the lower dose given for 3 weeks and the higher dose given for the rest of the treatment period summing up to 9 weeks of treatment. During the treatment period, 3 visits to the investigator will be scheduled in order to control blood pressure, renal function parameters and safety. In addition, parameters of endothelial function in the renal vasculature, based on a nephrological clearance investigation and a provocation with L-NMMA will be measured at baseline and after 9 weeks of treatment. Study Hypothesis: Due to the exploratory nature of the trial, the primary objective to evaluate the effect on RPF in response to L-NMMA infusion at baseline and after 9 weeks of therapy with either telmisartan 80 mg or ramipril 10 mg was not planned to be addressed by a test of prespecified hypotheses. Comparison(s): The change in RPF from baseline (Visit 4) to the end of treatment (Visit 7) in response to L-NMMA infusion was to be calculated as the change from the pre L-NMMA infusion (S1) to the end of the L-NMMA infusion (S2). A comparison of treatment groups was to be made using an analysis of covariance (ANCOVA) with pooled centre and treatment included as main effects and RPF (in response to L NMMA infusion) at baseline as a covariate. The treatment group difference, adjusted for the other factors in the model, was to be presented with a corresponding 95% confidence interval (CI) and a test of statistical significance. The model was also to be used to provide analysis results for the within treatment group changes.

Official Title
-----------------
A Prospective, Randomized, Double-blind, Double-dummy, Forced Titration, Parallel Group Comparison, Multicenter Trial to Compare the Effects of Either Telmisartan (40-80 mg p.o. Once Daily) or Ramipril (5-10 mg p.o. Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes

Conditions
-----------------
Diabetes Mellitus, Type 2, Hypertension

Intervention / Treatment
-----------------
* Drug: Telmisartan
* Drug: Ramipril


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hypertensive patients aged 30-80 years with type 2 diabetes, normo- or microalbuminuria, GFR > 80 mL/min (Cockroft-Gault) Exclusion Criteria: None

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Telmisartan|nan|
|Drug: Ramipril|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of renal plasma flow (RPF) in response to L-NMMA infusion at the end of treatment. |  | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of glomerular filtration rate (GFR) in response to L-NMMA infusion at the end of treatment |  | 9 weeks | 
| Change from baseline of filtration fraction (FF) in response to L-NMMA infusion at the end of treatment. |  | 9 weeks | 
| Change from baseline of renal vascular resistance (RVR) in response to L-NMMA infusion at the end of treatment. |  | 9 weeks | 
| Change from baseline of RPF in response to L-arginine infusion at the end of treatment. |  | 9 weeks | 
| Change from baseline of GFR in response to L-arginine infusion at the end of treatment |  | 9 weeks | 
| Change from baseline of FF in response to L-arginine infusion at the end of treatment. |  | 9 weeks | 
| Change from baseline of RVR in response to L-arginine infusion at the end of treatment. |  | 9 weeks | 
| Change from baseline of mean arterial pressure (MAP) and pulse rate (PR) in response to L-NMMA infusion at the end of treatment. |  | 9 weeks | 
| Change from baseline of MAP and PR in response to L-arginine infusion at the end of treatment. |  | 9 weeks | 
| Change from baseline of the laboratory parameters angiotensin II (ANG II), aldosterone, asymmetrical dimethylarginine (ADMA), L-arginine, urinary nitrate/nitrite (UNOx), and urinary albumin excretion at the end of treatment |  | 9 weeks | 
| Change from baseline of the pre-L-NMMA RPF at the end of treatment |  | 9 weeks | 
| Change from baseline of the pre-L-NMMA GFR at the end of treatment |  | 9 weeks | 
| Change from baseline of the pre-L-NMMA FF at the end of treatment. |  | 9 weeks | 
| Change from baseline of the pre-L-NMMA RVR at the end of treatment. |  | 9 weeks | 
| Change from baseline of the urinary excretion parameters creatinine, sodium, potassium, and urea at the end of treatment. |  | 9 weeks | 
| Blood pressure response and control at the end of treatment |  | 9 weeks | 
| Change from baseline of central blood pressure and augmentation index (by pulse wave analysis) at the end of treatment. |  | 9 weeks | 
| Change from baseline of RPF in response to Vitamin C infusion at the end of treatment |  | 9 weeks | 
| Change from baseline of GFR in response to Vitamin C infusion at the end of treatment |  | 9 weeks | 
| Change from baseline of FF in response to Vitamin C infusion at the end of treatment. |  | 9 weeks | 
| Change from baseline of RVR in response to Vitamin C infusion at the end of treatment. |  | 9 weeks | 
| Change from baseline of MAP and PR in response to Vitamin C infusion at the end of treatment. |  | 9 weeks | 
| Incidence of adverse events |  | week -2 and 9 weeks | 
| Changes from base line in routine laboratory data at the end of the study |  | 9 weeks | 
| Changes in vital signs |  | 9 weeks | 
| Changes from screening in physical examination at the end of the study |  | - 4 weeks and 9 weeks | 
| Changes from screening in ECG at the end of the study |  | - 4 weeks and 9 weeks |