PREVENTKD (Prevent Risks by Early interVEntion at Nighttime in Type 1 Diabetes for Kidney Disease) - Full Text View

Sponsor:	Northwestern University
Collaborators:	National Institutes of Health (NIH) Juvenile Diabetes Research Foundation
Information provided by:	Northwestern University
ClinicalTrials.gov Identifier:	NCT00729365

Purpose

The purpose of this study is to determine if the early treatment with a blood pressure medication (an ACE Inhibitor) can prevent or delay the development of kidney disease (microalbuminuria) in patients with Type 1 diabetes who have normal blood pressure and urine albumin levels.

Condition	Intervention	Phase
Type 1 Diabetes	Drug: Ramipril Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Nocturnal Hypertension and Prevention of Microalbuminuria in Type 1 Diabetes

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 1 High Blood Pressure Urine and Urination

Drug Information available for: Ramipril

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

Development of microalbuminuria (high urine albumin). Hypertension, urine and blood markers will also be evaluated for assessment of kidney disease state. [ Time Frame: at 3months and then every 6months during the 5years of the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

We will assess changes in the relative stiffness of your arteries (endothelial dysfunction) in persons with type 1 diabetes over the 5year study. [ Time Frame: year 1, 3, 5 and after the washout phase (5years and 1month) ] [ Designated as safety issue: No ]

Estimated Enrollment:	373
Study Start Date:	July 2008
Estimated Study Completion Date:	September 2013
Estimated Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
I: Placebo Comparator Subjects with normal nighttime blood pressure profile that decreases at night (Dippers). This group are all given placebo.	Drug: Placebo Dippers (category of subjects with a nighttime dip in blood pressure) will all be given Placebo. Control group.
II: Placebo Comparator Subjects with nighttime blood pressure that does not drop during the night (non-dippers). This group will be given placebo.	Drug: Placebo Subjects with nighttime blood pressure that does not drop during the night ("non-dippers") maybe randomized into the control group and given Placebo.
III: Active Comparator Subjects with nighttime blood pressure that does not drop during the night (non-dippers). This group will be given ACE inhibitor (study medication).	Drug: Ramipril ACE inhibitor known as Ramipril Subjects with nighttime blood pressure that does not drop during the night ("non-dippers") maybe randomized into this group and given an ACE inhibitor (study medication). Therefore, the "Non-Dippers" groups II and III will be randomized to receive either drug or placebo.

Detailed Description:

Only a fraction of persons with Type 1 diabetes (less than 40%) develop diabetic kidney disease (nephropathy). When the urinary albumin (a protein normally excreted in small amounts) is within the normal range, the prevalence of high blood pressure (hypertension) based on office blood pressure readings is very low. Many of these persons, however, develop nocturnal hypertension (high nighttime blood pressure) before the development of abnormally high urinary albumin excretion (a condition referred to as microalbuminuria). Currently, early treatment with medications called ACE inhibitors is only recommended after there is an indication of kidney damage, as reflected by the presence of microalbuminuria. Beginning ACE inhibitor therapy is currently not recommended prior to the development of microalbuminuria, unless patients have high blood pressure, because it would result in over-treatment of many people. By the time that microalbuminuria develops, however, kidney damage may be present and many patients will develop kidney disease. It would therefore be beneficial to identify those subjects who will develop microalbuminuria, so that treatment could be started early for those individuals. Persons who may go on to develop protein in their urine and eventual kidney disease perhaps could be identified on the basis of an abnormal fall (too little) in blood pressure at night. This pattern should not be confused with high blood pressure, but instead seen as an early indication present before the development of high blood pressure and microalbuminuria.

The purpose of the current study is therefore aimed at demonstrating that it is possible to prevent kidney disease in patients with type 1 diabetes and normal office blood pressure and urine protein excretion by selecting them on the basis of an abnormal fall in blood pressure at night. Moreover, this clinical trial will reveal the impact of long-term administration of an ACE inhibitor on nighttime blood pressure and also assess changes in the relative stiffness of blood vessels(endothelial dysfunction) in persons with type 1 diabetes over time.

Eligibility

Ages Eligible for Study:	13 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects with type 1 diabetes confirmed by C peptide measurements.
Male and Female subjects of all races will be included in this study.
Subjects age must be between 13 to 50 years
Duration of the disease (from time of diagnosis of diabetes) must be between 5 to 28 years.
Subjects must be normotensive defined as a systolic blood pressure of ≤ 130 mmHg and diastolic of ≤ 85 mmHg in subjects 18 and older and for children (ages 13-17) blood pressure will be in the normal range based on standard tables which takes in to account gender, height and age.
The mean 24 blood pressure must meet the same criteria as the office blood pressures outlined above.
Subject must have normoalbuminuria (UAE < 30 mg/24 hrs)
If subject is a female she must not be breast-feeding, and not of child-bearing potential, defined as post-menopausal for at least 1 year or surgically sterile; if she is of child bearing potential, then she must be practicing one of the following methods of birth control: 1) condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD), 2) contraceptives (oral or parenteral) initiated three months prior to study drug administration, 3) maintain a monogamous relationship with a vasectomized partner, or 4) total abstinence from sexual intercourse.

Exclusion Criteria:

Type 2 diabetics and other types of diabetics such as those with maturity onset diabetes or the young (MODY) will be excluded on the basis of established clinical criteria.
Subjects who have a history of hypertension or is taking any hypertensive medications.
Females who are pregnant or express a desire to become pregnant during the study. Females who are breast-feeding. Refer to details in inclusion criteria above regarding females.
Subjects who have a history of taking ACE inhibitors within the last six months or have a current indication for ACE inhibitor therapy.
Subjects (18 years of age and over) with a current blood pressure above 130mmHg/85mmHg. Subjects (13-17 years of age) who do not meet the normal range based on the standard tables
Subjects who are currently microalbuminuric i.e. 24hr albumin > 30mg
Subjects who have participated in an interventional clinical trial involving ABPM 6 months prior to this study.
Subjects that have a diagnosis of chronic atrial fibrillation.
Subjects with a lifestyle that would disrupt normal circadian rhythm (i.e. night-shift workers).
Subjects with a current serious co-morbid condition for which life expectancy is <2 years.
Subjects with a history of non-compliance, or psychiatric disturbance that would preclude successful completion of the study.
Inability to give informed consent.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00729365

Contacts

Contact: Daniel Batlle, MD

312-908-8342

d-batlle@northwestern.edu

Locations

United States, Florida
University of Florida	Not yet recruiting
Gainesville, Florida, United States, 32611
Contact: Karre Wetherington, CCRP 352-334-1469 kwether@UFL.EDU
Principal Investigator: Janet Silverstein, MD
Sub-Investigator: Micahel Haller, MD
Sub-Investigator: Loreen Loreen, MD
Sub-Investigator: Henry (Hank) Rohrs, MD
Sub-Investigator: Toree Malasanos, MD
Sub-Investigator: Lisa Gallo, MD
Sub-Investigator: Desmond Schatz, MD
Sub-Investigator: Sally Humphrey, ARNP
United States, Illinois
Northwestern University Feignberg School of Medicine	Recruiting
Chicago, Illinois, United States, 60611
Contact: Daniel Batlle 312-908-8342 d-batlle@northwestern.edu
Contact: Jacqui van Twest, BS, MS 312-908-6888 preventkd@northwestern.edu or j-van-twest@northwestern.edu
Principal Investigator: Daniel Batlle, MD
Sub-Investigator: Mark Molitch, MD
Sub-Investigator: Daniel Dunham, MD
Sub-Investigator: Vincent Yang, MD, BS
Sub-Investigator: William Schlueter, MD
Sub-Investigator: Craig Langman, MD
Sub-Investigator: Jennifer Tuazon, MD
Evanston Northwestern Healthcare	Not yet recruiting
Evanston, Illinois, United States, 60077
Contact: Herman Blomeier, MD 847-663-8540 h-blomeier@md.northwestern.edu
Contact: Mary Andreoni 847-663-8540 MAndreoni@enh.org
Principal Investigator: Lisa Purdy, MD
Sub-Investigator: Herman Blomeier, MD
University of Illinois at Chicago	Not yet recruiting
Chicago, Illinois, United States, 60612
Contact: Felecia Gilet, CRC 312-355-4442 fgilet@uic.edu
Principal Investigator: Barengolts Elena, MD
Sub-Investigator: Theodore Mazzone, MD
Sub-Investigator: Diego Ize-Ludlow, MD
Sub-Investigator: Terri Washington, MD
Sub-Investigator: Kristen Webb, NP
Sub-Investigator: Songya Pang, MD
Rush University Medical Center, Endocrinology Section	Recruiting
Chicago, Illinois, United States, 60612
Contact: Maripaz Vazquez 312-942-6163 Alexander_Lurie@rush.edu>
Principal Investigator: Alexander Lurie, MD
Sub-Investigator: David Baldwin, MD
University of Chicago	Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: George Bakris, MD 773-702-6138 gbakris@medicine.bsd.uchicago.edu
Principal Investigator: George Bakris, MD
Sub-Investigator: Lou Philipson, MD
Loyola University Chicago	Recruiting
Maywood, Illinois, United States, 60153
Contact: Barbara Sexton, RN, MS 708-216-8223 bsexton@lumc.edu
Principal Investigator: Maryann Emanuele, MD
Sub-Investigator: Carla Minutti, MD

Sponsors and Collaborators

Northwestern University

National Institutes of Health (NIH)

Juvenile Diabetes Research Foundation

Investigators

Principal Investigator:

Daniel Batlle, MD

Professor of Medicine and Chief Division of Nephrology/Hypertension

More Information

Additional Information:

Northwestern Feinberg School of Medicine website: application form, general and contact information This link exits the ClinicalTrials.gov site

PREVENTKD website: for study coordination This link exits the ClinicalTrials.gov site

Publications:

Lurbe E, Redon J, Kesani A, Pascual JM, Tacons J, Alvarez V, Batlle D. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med. 2002 Sep 12;347(11):797-805.

Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, Den Hond E, McCormack P, Staessen JA, O'Brien E. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005 Jul;46(1):156-61. Epub 2005 Jun 6.

Lurbe A, Redón J, Pascual JM, Tacons J, Alvarez V, Batlle DC. Altered blood pressure during sleep in normotensive subjects with type I diabetes. Hypertension. 1993 Feb;21(2):227-35.

Haller MJ, Stein J, Shuster J, Theriaque D, Silverstein J, Schatz DA, Earing MG, Lerman A, Mahmud FH. Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatr Diabetes. 2007 Aug;8(4):193-8.

Responsible Party:	Northwestern University Feinberg School of Medicine ( Dr Daniel Batlle, M.D. Professor of Medicine and Chief, Division of Nephrology / Hypertension )
Study ID Numbers:	1 U01 DK071733-01A1, JDRF 8-2008-335
Study First Received:	August 4, 2008
Last Updated:	October 29, 2008
ClinicalTrials.gov Identifier:	NCT00729365 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Northwestern University:

Urine albumin excretion rates
Nighttime and daytime blood pressure
Endothelial Dysfunction

Additional relevant MeSH terms:

Metabolic Diseases
Autoimmune Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Diabetes Mellitus
Endocrine System Diseases
Enzyme Inhibitors
Cardiovascular Agents

Antihypertensive Agents
Ramipril
Pharmacologic Actions
Protease Inhibitors
Diabetes Mellitus, Type 1
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on February 08, 2010