Diabetes Mellitus, Type 2, Hypertension
Conditions
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.
Interventions
DRUGTelmisartan
DRUGRamipril
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Hypertensive patients aged 30-80 years with type 2 diabetes, normo- or microalbuminuria, GFR \> 80 mL/min (Cockroft-Gault)
Exclusion criteria
None
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline of renal plasma flow (RPF) in response to L-NMMA infusion at the end of treatment. | 9 weeks |
Secondary
| Measure | Time frame |
|---|---|
| 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 glomerular filtration rate (GFR) in response to L-NMMA infusion 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 |
| Change from baseline of the urinary excretion parameters creatinine, sodium, potassium, and urea at the end of treatment. | 9 weeks |
Countries
France, Germany, Spain
Outcome results
None listed