Bosentan Use in Patients With Diabetic Nephropathy - Full Text View

Sponsors and Collaborators:	Centre hospitalier de l'Université de Montréal (CHUM) Actelion
Information provided by:	Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier:	NCT00638131

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes	Drug: bosentan	Phase III

MedlinePlus related topics: Diabetes Diabetic Kidney Problems

Drug Information available for: Bosentan Angiotensin II Angiotensin II, ile(5)-

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Effect of Bosentan on Systemic and Renal Inflammatory Markers in Patients With Diabetic Nephropathy on Angiotensin II Receptor Blockers

Further study details as provided by Centre hospitalier de l'Université de Montréal (CHUM):

Primary Outcome Measures:

change from baseline to week 16 in renal inflammation. The following urinary inflammatory/oxidative stress parameters will be measured: - TNF [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

change from baseline to week 16 in renal functioning. The following renal function parameter will be measured: - 24h UAE; [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	35
Study Start Date:	June 2008
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Bosentan 62.5mg bid x4 weeks; up-titrated to 125mg bid x12 weeks;	Drug: bosentan 62.5mg bid x4 weeks, up-titrate to 125mg bid x12 weeks
2: Placebo Comparator placebo given bid same as experimental arm;	Drug: bosentan 62.5mg bid x4 weeks, up-titrate to 125mg bid x12 weeks

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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;

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00638131

Contacts

Contact: Genevieve Renier, MD, PhD

514-890-8000 ext 26895

genevieve.renier@umontreal.ca

Locations

Canada, Quebec
CHUM	Recruiting
Montreal, Quebec, Canada, H2L 4M1
Principal Investigator: Maryse Courteau, MD
Sub-Investigator: Geneviève Renier, MD, PhD

Sponsors and Collaborators

Centre hospitalier de l'Université de Montréal (CHUM)

Actelion

Investigators

Principal Investigator:

Maryse Courteau, MD

CHUM

More Information

Responsible Party:	CHUM ( Dr. Geneviève Renier )
Study ID Numbers:	BOS-ND-2007
Study First Received:	March 12, 2008
Last Updated:	September 17, 2008
ClinicalTrials.gov Identifier:	NCT00638131
Health Authority:	Canada: Health Canada

Study placed in the following topic categories:

Diabetic Nephropathies
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Angiotensin II
Bosentan
Urologic Diseases

Diabetes Mellitus, Type 2
Kidney Diseases
Endocrinopathy
Glucose Metabolism Disorders
Metabolic disorder
Diabetes Complications

Additional relevant MeSH terms:

Therapeutic Uses
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009