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

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ClinicalTrials.gov Identifier: NCT00118976
Recruitment Status : Completed
First Posted : July 12, 2005
Last Update Posted : November 23, 2006
Sponsor:
Information provided by:
Steno Diabetes Center

Study Description
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Brief 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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type I Diabetic Nephropathy Drug: Lisinopril Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Primary Purpose: Prevention
Official Title: Optimal Dose of ACE Inhibitor for Treatment of Diabetic Nephropathy in Type 1 Diabetic Patients With Hypertension and Diabetic Nephropathy
Study Start Date : March 2005
Study Completion Date : September 2006

Resource links provided by the National Library of Medicine

Drug Information available for: Lisinopril

Arms and Interventions
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Outcome Measures
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Primary Outcome Measures :
  1. albuminuria

Secondary Outcome Measures :
  1. blood pressure (24 hour ambulatory) and GFR.
  2. Tertiary: differences in response to treatment in patients with different ACE/ID and other renin angiotensin system genotypes.

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00118976


Locations
Denmark
Steno Diabetes Center
Gentofte, Denmark, 2820
Sponsors and Collaborators
Steno Diabetes Center
Investigators
Study Chair: Hans-Henrik Parving, MD Steno Diabetes Center
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

ClinicalTrials.gov Identifier: NCT00118976     History of Changes
Other Study ID Numbers: mace
First Posted: July 12, 2005    Key Record Dates
Last Update Posted: November 23, 2006
Last Verified: November 2006

Keywords provided by Steno Diabetes Center:
diabetic nephropathy
type 1 diabetes
albuminuria
hypertension

Additional relevant MeSH terms:
Diabetes Mellitus
Kidney Diseases
Diabetic Nephropathies
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
Autoimmune Diseases
 Immune System Diseases
Lisinopril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs