Angiotensin II Antagonism of TGF-Beta 1

• Status: Completed
• Trial end date: 2004-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Diabetic nephropathy is a frequent microvascular complication that occurs in approximately 40% of patients with either type 1 or type 2 diabetes. The most common cause of end-stage renal disease (ESRD) in the United States and in the developed world is diabetic nephropathy. Currently, more than half the United States ESRD population has diabetes. More effective therapies to prevent and treat diabetic nephropathy are urgently needed. One way to increase therapeutic effectiveness is to refine treatment targets based on improved understanding of how treatments modulate disease processes. The purpose of this study is to determine whether a treatment for diabetic nephropathy, the angiotensin receptor blocker candesartan, modifies mediators of kidney injury independent of blood pressure and the relationships to drug dose.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Providence Health & Services
• Collaborator: AstraZeneca
• Treatments: Angiotensin II; Angiotensinogen; Candesartan; Candesartan cilexetil

Criteria

Inclusion Criteria:

• Type 2 diabetes

• Nephropathy (proteinuria >500 mg/day)

• Chronic Hypertension (as determined by current antihypertensive therapy and/or an average of diastolic blood pressure greater than 90 mmHg or greater or systolic blood pressure of 140 mmHg confirmed on at least two subsequent visits over one week or more).

Exclusion Criteria:

• Conditions associated with elevated TGF-Beta (e.g. rheumatoid arthritis, cancer, etc.).

• Conditions associated with alterations in serum levels of PIP and/or CITP (liver cirrhosis, osteoporosis, hyperthyroidism, multiple myeloma, osteolytic metastases, and systemic glucocorticoid treatment

• History of Stage III hypertension (diastolic BP > 110 mmHg or systolic BP > 180 mmHg) or a history of hypertensive urgency or emergency.

• NYHA Class III or IV heart failure

• Calculated creatinine clearance of less than 30 ml/min or serum creatinine > 3 mg/dL

• HbA1c > 10%

• Patients unable to be withdrawn for 2 weeks from AT-II antagonist or ACE- inhibitor therapy

• Blood Pressure <140/90 is unachievable in the absence of an AT-II antagonist or ACE-inhibitor