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 Copenhagen

Study Description

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

MedlinePlus Genetics related topics: Hypertension Type 1 diabetes

MedlinePlus related topics: Diabetic Kidney Problems Kidney Diseases

Drug Information available for: Lisinopril

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

albuminuria

Secondary Outcome Measures :

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.

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

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

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Denmark
Steno Diabetes Center
Gentofte, Denmark, 2820

Sponsors and Collaborators

Steno Diabetes Center Copenhagen

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schjoedt KJ, Astrup AS, Persson F, Frandsen E, Boomsma F, Rossing K, Tarnow L, Rossing P, Parving HH. Optimal dose of lisinopril for renoprotection in type 1 diabetic patients with diabetic nephropathy: a randomised crossover trial. Diabetologia. 2009 Jan;52(1):46-9. doi: 10.1007/s00125-008-1184-8. Epub 2008 Oct 31.

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ClinicalTrials.gov Identifier:	NCT00118976
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 Copenhagen:


diabetic nephropathy type 1 diabetes albuminuria hypertension

Additional relevant MeSH terms:

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Kidney Diseases Diabetic Nephropathies Diabetes Mellitus, Type 1 Urologic Diseases Diabetes Complications Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases 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

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