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

November 22, 2006 updated by: Steno Diabetes Center Copenhagen

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Gentofte, Denmark, 2820
        • Steno Diabetes center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
albuminuria

Secondary Outcome Measures

Outcome Measure
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Steno Diabetes Center Copenhagen

Investigators

  • Study Chair: Hans-Henrik Parving, MD, Steno Diabetes Center Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Study Completion

September 1, 2006

Study Registration Dates

First Submitted

July 1, 2005

First Submitted That Met QC Criteria

July 1, 2005

First Posted (Estimate)

July 12, 2005

Study Record Updates

Last Update Posted (Estimate)

November 23, 2006

Last Update Submitted That Met QC Criteria

November 22, 2006

Last Verified

November 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • mace

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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