ET-blockade and Exercise-induced Vascular Adaptations in T2DM

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to establish the effect of ET blockade on vascular adaptations during an 8-week exercise program in subjects with T2DM. We hypothesize that combining ET - blockade with exercise training leads to an acute increase of exercise induced blood flow when compared with exercise alone. We expect that this will lead to an optimization of vascular training effect in T2DM.

Official Title
-----------------
Effect of a Dual ET(Endothelin)-Blocker on Exercise Induced Vascular Adaptations in Type 2 Diabetes Mellitus (T2DM)

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Bosentan
* Drug: Placebo
* Behavioral: Exercise


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 Diabetes Mellitus (>2 years since diagnosis) OR controls Exclusion Criteria: <40 years of age >65 years of age smoking cardiovascular disease diabetes related manifest vascular complications Type 1 Diabetes Mellitus use of Glibenclamide use of HIV drugs use of calcineurin inhibitors use of drugs that interfere with CYP3A4 and CYP2C19

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bosentan + Exercise<br>2x/day 62.5 mg Bosentan for 4 weeks alongside 3x/week supervised exercise 2x/day 125 mg Bosentan for 4 weeks alongside 3x/week supervised exercise | Drug: Bosentan<br> <br> * Other names: actelion pharmaceuticals;Behavioral: Exercise<br>* Supervised exercise training program of 8 weeks, for 3x/week<br>* Other names: Supervised Exercise Training Program;|
| Placebo Comparator: Placebo + Exercise<br>2x/day 62.5 mg Placebo for 4 weeks alongside 3x/week supervised exercise 2x/day 125 mg Placebo for 4 weeks alongside 3x/week supervised exercise | Drug: Placebo<br> <br> * Other names: actelion pharmaceuticals;Behavioral: Exercise<br>* Supervised exercise training program of 8 weeks, for 3x/week<br>* Other names: Supervised Exercise Training Program;|
| Other: Exercise<br>3x/week supervised exercise for 8 weeks | Behavioral: Exercise<br>* Supervised exercise training program of 8 weeks, for 3x/week<br>* Other names: Supervised Exercise Training Program;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow mediated dilation |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conduit Artery Dilator Capacity |  | 8 weeks | 
| Intima-Media Thickness |  | 8 weeks | 
| Maximal Oxygen Uptake |  | 8 weeks |