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

This study has been completed.
Sponsor:
Information provided by:
Steno Diabetes Center
ClinicalTrials.gov Identifier:
NCT00118976
First received: July 1, 2005
Last updated: November 22, 2006
Last verified: November 2006
  Purpose

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 Intervention
Diabetes Mellitus, Type I
Diabetic Nephropathy
Drug: Lisinopril

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by Steno Diabetes Center:

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.

Estimated Enrollment: 60
Study Start Date: March 2005
Estimated Study Completion Date: September 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided by Steno Diabetes Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00118976     History of Changes
Other Study ID Numbers: mace
Study First Received: July 1, 2005
Last Updated: November 22, 2006
Health Authority: Denmark: National Board of Health

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

Additional relevant MeSH terms:
Diabetic Nephropathies
Diabetes Mellitus
Kidney Diseases
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
Autoimmune Diseases
Immune System Diseases
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014