Bosentan Use in Patients With Diabetic Nephropathy

Type 2 Diabetes Clinical Trial

Official title:

Effect of Bosentan on Systemic and Renal Inflammatory Markers in Patients With Diabetic Nephropathy on Angiotensin II Receptor Blockers

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00638131
• Other study ID #: BOS-ND-2007
• Status: Terminated
• Phase: Phase 3
• Start date: January 2009
• Est. completion date: June 2010

Study information

• Verified date: June 2010
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There is little doubt of the necessity for further improvement in the prevention and therapy of end-stage renal disease. Despite the success of ARB in treating diabetic nephropathy, not all patients obtain satisfactory control of blood pressure, albuminuria and decline in renal function. Experimental data have provided us with a rationale for the potential added benefits of ET receptor blockade to the AII inhibition in diabetic renal protection. Considering the nephroprotective effect of bosentan in diabetic rats, clinical studies are warranted to assess whether ET receptor antagonism has additive renoprotective effects on top of AII inhibition.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: June 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Men or women = 18 years of age with a body weight of = 40 kg;

• For female patients, only non-pregnant women who are surgically sterile, postmenopausal or have documented infertility (over 50 years of age and amenorrheic for at least 1 year), or those of childbearing potential using intrauterine devices (IUDs);

• Patients diagnosed Type 2 diabetes with overt nephropathy (urinary albumin excretion = 300mg/24h);

• Patients on current treatment with angiotensin II receptor blockers for = 3 months;

• Patients stable for at least 3 months prior to screening (no change in medications for diabetic nephropathy);

• Provide written informed consent;

Exclusion Criteria:

• Patients with a history of pulmonary chronic obstructive disease, cardiac failure or coronary artery disease;

• Patients with documented cancers, acute infections or chronic inflammatory diseases;

• Patients who are pregnant or breast-feeding;

• Patients with known hepatic disorders or AST and /or ALT upper than normal limit;

• Patients with hemoglobin or hematocrit that is = 30% below the normal range (patients with secondary polycythemia are permitted);

• Patients with systolic blood pressure < 110mm Hg;

• Patients with plasmatic albumin level < 30g/L;

• Patients with a documented creatinine clearance = 60ml/min;

• Patients on anticoagulants or anti-inflammatory drugs, including cyclooxygenase inhibitors, AINS, prednisone and immunosuppressive drugs, platelet aggregation inhibitors, except low dose aspirin, ACE inhibitors, antidiabetic agents (rosiglitazone, pioglitazone) and antioxidants (vitamin E)(except statins or low-dose aspirin = 80mg/day);

• Patients on treatment or planned treatment with another investigational drug;

• Patients who are receiving an endothelin receptor antagonist, phosphodiesterase type 5 inhibitor, or with a prostanoid (excluding acute administration during a catheterization procedure to test vascular reactivity) within 2 months of inclusion;

• Patients who are receiving calcineurin-inhibitors (i.e., cyclosporine A and tacrolimus), fluconazole, glibenclamide (glyburide) at inclusion or are expected to receive any of these drugs during the study;

• Patients with a known hypersensitivity to bosentan or any of the excipients;

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Type 2 Diabetes

Intervention

Drug:
• bosentan
62.5mg bid x4 weeks, up-titrate to 125mg bid x12 weeks

Locations

Country	Name	City	State
Canada	CHUM	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)	Actelion

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change from baseline to week 16 in renal inflammation. The following urinary inflammatory/oxidative stress parameters will be measured: - TNF		16 weeks
Secondary	change from baseline to week 16 in renal functioning. The following renal function parameter will be measured: - 24h UAE;		16 weeks