Maximal Dose of Angiotensin Converting Enzyme (ACE) Inhibitor for Treatment of Diabetic Kidney Disease

Diabetic Nephropathy Clinical Trial

Official title:

Optimal Dose of ACE Inhibitor for Treatment of Diabetic Nephropathy in Type 1 Diabetic Patients With Hypertension and Diabetic Nephropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00118976
• Other study ID #: mace
• Status: Completed
• Phase: N/A
• First received: July 1, 2005
• Last updated: November 22, 2006
• Start date: March 2005
• Est. completion date: September 2006

Study information

• Verified date: November 2006
• Source: Steno Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: National Board of Health
• Study type: Interventional

Clinical Trial Summary

The primary aim is to evaluate the anti proteinuric effect of increasing doses of the ACE inhibitor, lisinopril: 20, 40 and 60 mg daily in type 1 diabetic patients with hypertension and diabetic nephropathy.

The secondary aim is to evaluate the effect on blood pressure (24 hour ambulatory blood pressure) and kidney function (glomerular filtration rate (GFR)).

The tertiary aim is to evaluate differences in response to treatment according to ACE/insertion/deletion (ID)-genotypes and other genetic variants in the genes of the renin angiotensin system.

Description:

This is a randomized, double-blind cross-over study with three treatment periods consisting of 20, 40 and 60 mg lisinopril daily in random order. The endpoints of the study will be examined after each treatment period. There is no wash out between treatment periods. To minimize the risk of hypotension every treatment period starts with 20 mg lisinopril for two weeks. Thus, the risk of adverse effects is minimized and an increase in dose from 0 mg to 60 mg lisinopril is avoided.

The patients usual antihypertensive treatments will be stopped in a period of 8 weeks (wash out) before randomization. Since diuretic drugs will be needed by almost every patient in the study to avoid oedema all patients will be treated with lasix retard 60 – 120 mg daily.

Patients:

60 type 1 diabetic patients with diabetic nephropathy and hypertension (blood pressure > 135 mm Hg systolic and/or 85 mm Hg diastolic).

Methods:

The endpoints of the study will be examined at baseline and after each treatment period corresponding to 8, 16, and 24 weeks after randomization. The following parameters are determined after each treatment period: Albuminuria (determined from three consecutive 24 hours urine collections), kidney function (GFR – by plasma clearance of 51Cr-EDTA ), and 24 hour ambulatory blood pressure (TM-2420/2421). Furthermore, the concentrations of TGF-ß, sodium, creatinine, and carbamide in the 24 hour urinary samples are determined. The plasma concentration of albumin, renin, angiotensin II, and aldosterone is measured.

DNA is extracted from a blood sample and genetic variants in the renin-angiotensin system are measured including the ACE/ID genotype.

Endpoints:

Primary endpoint: albuminuria ; Secondary endpoints: blood pressure (24 hour ambulatory) and GFR; Tertiary: differences in response to treatment in patients with different ACE/ID and other renin angiotensin system genotypes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Type 1 diabetes (WHO criteria)

• Diabetic nephropathy (2 out of 3 consecutive 24 hour urinary samples with albumin excretion > 300 mg/24hour and diabetic retinopathy in the absence of signs of other kidney or urinary tract disease) 27 or diabetic glomerulosclerosis verified by biopsy.

• Hypertension: Blood pressure > 135 mmHg systolic and/or 85 mm Hg diastolic repeatedly.

• Age from 18 to 70 years.

Exclusion Criteria:

• Age < 18 years or > 70 years.

• Pregnancy or fertile women not using adequate anticonceptive (intrauterine device, sterilization, or oral anticonceptive)

• Malignant hypertension.

• Blood pressure > 180/105 mm Hg

• Known renal artery stenosis

• GFR < 30 ml/min/1.73 m²

• Serum potassium > 4.8 mmol/ l

• Heart failure, myocardial infarction, unstable angina or coronary bypass operation within the previous three months.

• Abuse of drugs or alcohol.

• Not able to understand the written information.

• Known intolerance to ACE inhibitors.

• Chronic use of non steroid inflammatory drugs or aspirin (above 1 g/day)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type I
• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Intervention

Drug:
• Lisinopril

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center	Gentofte

Sponsors (1)

Lead Sponsor	Collaborator
Steno Diabetes Center

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	albuminuria
Secondary	blood pressure (24 hour ambulatory) and GFR.
Secondary	Tertiary: differences in response to treatment in patients with different ACE/ID and other renin angiotensin system genotypes.