Renal and Systemic Effects of NCX4016 in Patients With Type 2 Diabetes and Early Nephropathy

• Status: Terminated
• Trial end date: 2004-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Aspirin is commonly used for treatment of painful and inflammatory diseases and in the prevention of the cardiovascular disease. A major drawback of aspirin treatment is the well recognized gastrointestinal toxicity. Recent research indicate that coupling a nitric oxide (NO)derivate to the aspirin moiety retains its therapeutic effects while avoiding its undesirable gastrointestinal side effects. NO has cytoprotective effects, such as blood flow modulation, mucus release and repair of mucosal injury. NCX4016, a NO-releasing derivative of acetylsalicilic acid, has been shown to retain the analgesic, anti-inflammatory and antithrombotic activity of aspirin, but with less gastrointestinal toxicity. In addition, preliminary data suggested that NCX4016 may restore insulin sensitivity in eNOS deficient mice.

This study was aimed to evaluate the activity of NCX4016, compared to aspirin, on albuminuria, insulin sensitivity and cardiac and renal hemodynamic in patients with type 2 diabetes mellitus. The patients after one month of placebo treatment, entered two 1-month treatments periods, with equivalent doses (800 mg of NCX4016, 325 mg of aspirin) of NCX4016 or aspirin.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Treatments: Nitroaspirin

Criteria

Inclusion Criteria:

• Male and female patients affected by type 2 diabetes with stable metabolic control (HbA1c < 9%), and stable systemic blood pressure control (SBP/ DBP < 160/90 mmHg).

• Presence of early nephropathy (overnight albumin excretion rate > 20 microg/ min for at least 6 months), without overt renal insufficiency (serum creatinine concentration < 2 mg/dl).

• Age between 18 and 75 years.

• Written signed informed consent; patient willing and able to comply with all study procedures and scheduled visits.

Exclusion Criteria:

• History of any form of allergic reactions or hypersensitivity or intolerance or contraindication to acetylsalicylic acid or nitrates.

• Patients under the age of 18 or above 75.

• Patients who are not able to give an informed consent or inadequate comprehension of study risks and requirements.

• Patients who are unable to comply with the requirements of the study protocol.

• Chronic alcohol or drug abuse (current or within the past year).

• Pregnancy and lactation.

• If women of child-bearing potential, a pregnancy test must be performed before inclusion and after the study, and reliable contraceptive methods followed.

• Evidence for non-diabetic renal disease.

• Patients with duodenal/gastric ulcer history, or gastrointestinal bleeding over the last 6 months.

• Patients with liver insufficiency (ASAT, ALAT > 2 times the upper normal limit).

• Patients with platelet counts < 100,000 cells/mm3.

• Patients with hemorrhagic diathesis.

• Patients on antiinflammatory or immunosuppressive therapy over the last 6 months.