Bosentan Use in Patients With Diabetic Nephropathy

This study has been terminated.
(problem of recruitment)
Sponsor:
Collaborator:
Actelion
Information provided by:
Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier:
NCT00638131
First received: March 12, 2008
Last updated: June 14, 2010
Last verified: June 2010
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Bosentan on Systemic and Renal Inflammatory Markers in Patients With Diabetic Nephropathy on Angiotensin II Receptor Blockers

Resource links provided by NLM:


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 ]

Enrollment: 1
Study Start Date: January 2009
Study Completion Date: June 2010
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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
Other Name: Tracleer
Placebo Comparator: 2
placebo given bid same as experimental arm;
Drug: bosentan
62.5mg bid x4 weeks, up-titrate to 125mg bid x12 weeks
Other Name: Tracleer

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Canada, Quebec
CHUM
Montreal, Quebec, Canada, H2L 4M1
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Actelion
Investigators
Principal Investigator: Maryse Courteau, MD CHUM
  More Information

No publications provided

Responsible Party: Dr. Geneviève Renier, CHUM
ClinicalTrials.gov Identifier: NCT00638131     History of Changes
Other Study ID Numbers: BOS-ND-2007
Study First Received: March 12, 2008
Last Updated: June 14, 2010
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Kidney Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
Bosentan
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014