Treatment of Diabetic Nephropathy - Full Text View

Sponsored by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00065559

Purpose

COX-2 is an enzyme that is found in several different tissues in the body. COX-2 appears to produce a substance called prostaglandins, mainly at sites of inflammation. Several drugs have been approved by the FDA that inhibit COX-2 such as celecoxib, or brand name Celebrex®. These drugs are primarily used in patients with osteoarthritis and rheumatoid arthritis to decrease inflammation and pain. COX-2 inhibitors have been developed because they are more selective in treatment of inflammation and pain and tend to have fewer gastrointestinal side effects than NSAIDs (nonsteroidal anti-inflammatory drugs) such as aspirin, ibuprofen, naproxen, etc.

The normal adult kidney expresses COX-2 in various regions. Prostaglandins, which are produced in the kidney by COX-2, may contribute to glomerular and tubulointerstitial inflammatory diseases (types of kidney diseases due to inflammation). In some animal studies, COX-2 inhibitors have been shown to be potentially beneficial in reducing the amount of protein spilled in the urine and preserving kidney function with these inflammatory kidney diseases.

This study will compare the effects of COX-2 inhibitor to placebo (an inactive substance) in patients with diabetic nephropathy (kidney disease due to diabetes) and proteinuria (spilling protein in the urine) on 24-hour urinary protein excretion.

This study is designed to see whether COX-2 inhibitors are useful in treating diabetic patients with kidney disease. The purpose of this study is a short-term pilot study that will allow the gathering of important data such as the ability to carry out the study and carry it out safely. Subjects with proteinuria and diabetic kidney disease already on ACE (Angiotensin-Converting Enzyme) inhibitor or ARB (Angiotensin Receptor Blocker) therapy (types of blood pressure medicines) will be randomized to a type of study in which each subject will serve as their own control. The study is set up so that each subject will receive either the COX-2 inhibitor or placebo for a period followed by a period of no drug and then followed by a period of receiving either the COX-2 inhibitor or placebo (whichever they did not receive the first period).

Condition	Intervention
Diabetic Nephropathy	Drug: celecoxib

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study

Resource links provided by NLM:

MedlinePlus related topics: Diabetic Kidney Problems

Drug Information available for: Celecoxib

U.S. FDA Resources

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Estimated Enrollment:	30
Study Start Date:	April 2003
Estimated Study Completion Date:	December 2004

Detailed Description:

The study is designed with a screening period, a baseline period and a treatment period. The purpose of screening is to identify eligible subjects and to exclude ineligible subjects. A careful history and physical examination will be conducted to ensure that the subject meets all the inclusion criteria and does not meet any of the exclusion criteria. The screening period lasts from 2 days to 2 months in duration.

The baseline period is from 2 – 3 months in duration. During the first baseline visit, there is withdrawal of previously used angiotensin converting enzyme inhibitors or angiotensin receptor antagonists (if any) and the initiation of quinapril 20 mg daily therapy (or irbesartan --150 - 300 mg daily).

The subject will then be seen as frequently as determined by the investigator for subject’s safety. The purpose of the second baseline visit is to determine safety after the initiation of therapy quinapril 20 mg po per day (or irbesartan 150 - 300 mg per day). The purpose of third baseline visit is to insure that the subject meets all the inclusion and none of the exclusion criteria prior to randomization. In addition, it will be assured that the subject’s blood pressure is at a safe level to proceed with randomization and the laboratory and urinary collections will be made.

Only those subjects who fulfill all inclusion and none of the exclusion criteria will proceed to randomization. Also, in order to proceed to the randomization phase of the study, the subject must have a blood pressure of less than or equal to 135/85mmHg.

The treatment phase will consist of 18 weeks. During the treatment phase, the subject will be followed for safety and efficacy. The subjects will be randomly assigned to COX-2 inhibitor for 6 weeks (1st 6 week cycle), washout 3 weeks, placebo 6 weeks (2nd 6 week cycle), washout 3 weeks or to placebo 6 weeks (1st 6 week cycle), washout 3 weeks, COX-2 inhibitor 6 weeks (2nd 6 week cycle), washout 3 weeks.

During baseline and treatment periods, interim visits will be held in order to address blood pressure control or other problems that the patient or the PI deems necessary for protocol adherence.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18 years or greater
Men or non-pregnant, non-lactating women with Type 1 or Type II diabetes and renal disease
24-hour urinary protein excretion greater than or equal to 500 mg
Serum creatinine less than or equal to 3 mg/dl
Willingness and ability to give informed consent and to cooperate with the protocol including discontinuing current antihypertensive medications if necessary

Exclusion Criteria:

Pregnant or lactating women
Renal disease other than diabetic nephropathy
Renal Transplant or on dialysis
Immunosuppressive agents for greater than 2 weeks in the 3 months prior to randomization (inhaled steroids are permissible)
Renal vascular disease (uncorrected and hemodynamically significant)
Obstructive uropathy (uncorrected and hemodynamically significant)
History or evidence of acute renal failure within 6 months prior to randomization visit
Serum potassium greater than 5.2 mEq/L
Known human immunodeficiency virus disease (HIV)
Any major disorder which in the opinion of the investigator would reduce life expectancy during the course of this study or could preclude participation in this or could adversely effect the interpretation of the data.
Anticipated inability to cooperate with or any condition of sufficient severity to impair participation in the study.
Any of the following cardiovascular conditions within 1 month of the screening visit: myocardial infarction, coronary angioplasty, coronary artery bypass graft, other revascularization procedure, severe or unstable angina, stroke, transient ischemic attack or hemodynamically important vascular disease.
Need for chronic (greater than 2 weeks) immunosuppressive therapy including oral or IV corticosteroids. (Inhaled steroids are permissible.)
History of drug sensitivity or adverse reaction to both ACE I and ARB.
History of drug sensitivity, allergy, or adverse reaction to COX-2 inhibitor, aspirin, or sulfonamides.
Evidence or suspicion of drug abuse or excessive alcohol consumption within 12 months prior to screening visit 1.
Receipt of any investigational drug within 30 days or 5 half-lives of the investigational drug (the longer period will apply) before screening visit 1.
Active psychiatric disorder.
History of peptic ulcer disease and/or gastrointestinal bleeding.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00065559

Locations

United States, Illinois
Rush Presbyterian St. Luke's Medical Center
Chicago, Illinois, United States, 60612
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

More Information

No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Sinsakul M, Sika M, Rodby R, Middleton J, Shyr Y, Chen H, Han E, Lehrich R, Clyne S, Schulman G, Harris R, Lewis J. A randomized trial of a 6-week course of celecoxib on proteinuria in diabetic kidney disease. Am J Kidney Dis. 2007 Dec;50(6):946-51.

Study ID Numbers:	TRMTDN
Study First Received:	July 28, 2003
Last Updated:	February 16, 2007
ClinicalTrials.gov Identifier:	NCT00065559 History of Changes
Health Authority:	United States: Federal Government

Study placed in the following topic categories:

Celecoxib
Diabetic Nephropathies
Urologic Diseases
Diabetes Mellitus

Endocrine System Diseases
Endocrinopathy
Kidney Diseases
Diabetes Complications

Additional relevant MeSH terms:

Diabetic Nephropathies
Urologic Diseases
Diabetes Mellitus

Endocrine System Diseases
Kidney Diseases
Diabetes Complications

ClinicalTrials.gov processed this record on July 02, 2009