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

Primary Purpose

Type 1 Diabetes

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Ramipril
Placebo
Placebo
Sponsored by
Northwestern University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Type 1 Diabetes focused on measuring Urine albumin excretion rates, Nighttime and daytime blood pressure, Endothelial Dysfunction

Eligibility Criteria

13 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Florida
  • Northwestern University Feinberg School of Medicine
  • Rush University Medical Center, Endocrinology Section
  • University of Illinois at Chicago
  • University of Chicago
  • Loyola University Chicago

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Placebo Comparator

Active Comparator

Arm Label

Dippers - Placebo Treated

NonDippers - Placebo Treated

NonDippers - Ramipril Treated

Arm Description

Subjects with normal nighttime blood pressure profile that decreases at night (Dippers). This group are all given placebo.

Subjects with nighttime blood pressure that does not drop during the night (non-dippers). This group will be given placebo.

Subjects with nighttime blood pressure that does not drop during the night (non-dippers). This group will be given ACE inhibitor (study medication).

Outcomes

Primary Outcome Measures

Development of Microalbuminuria (High Urine Albumin). Hypertension, Urine and Blood Markers Will Also be Evaluated for Assessment of Kidney Disease State.

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.

Full Information

First Posted
August 4, 2008
Last Updated
February 24, 2015
Sponsor
Northwestern University
Collaborators
Juvenile Diabetes Research Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00729365
Brief Title
PREVENTKD (Prevent Risks by Early interVEntion at Nighttime in Type 1 Diabetes for Kidney Disease)
Acronym
PREVENTKD
Official Title
Nocturnal Hypertension and Prevention of Microalbuminuria in Type 1 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Terminated
Why Stopped
Data from other studies showed that study could not be completef successfully
Study Start Date
July 2008 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwestern University
Collaborators
Juvenile Diabetes Research Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Urine albumin excretion rates, Nighttime and daytime blood pressure, Endothelial Dysfunction

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dippers - Placebo Treated
Arm Type
Placebo Comparator
Arm Description
Subjects with normal nighttime blood pressure profile that decreases at night (Dippers). This group are all given placebo.
Arm Title
NonDippers - Placebo Treated
Arm Type
Placebo Comparator
Arm Description
Subjects with nighttime blood pressure that does not drop during the night (non-dippers). This group will be given placebo.
Arm Title
NonDippers - Ramipril Treated
Arm Type
Active Comparator
Arm Description
Subjects with nighttime blood pressure that does not drop during the night (non-dippers). This group will be given ACE inhibitor (study medication).
Intervention Type
Drug
Intervention Name(s)
Ramipril
Other Intervention Name(s)
ACE Inhibitor
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Dippers (category of subjects with a nighttime dip in blood pressure) will all be given Placebo. Control group.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subjects with nighttime blood pressure that does not drop during the night ("non-dippers") maybe randomized into the control group and given Placebo.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark E Molitch, MD
Organizational Affiliation
Professor of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Rush University Medical Center, Endocrinology Section
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Loyola University Chicago
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
12226150
Citation
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. doi: 10.1056/NEJMoa013410.
Results Reference
background
PubMed Identifier
15939805
Citation
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. doi: 10.1161/01.HYP.0000170138.56903.7a. Epub 2005 Jun 6.
Results Reference
background
PubMed Identifier
8428785
Citation
Lurbe A, Redon 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. doi: 10.1161/01.hyp.21.2.227.
Results Reference
background
PubMed Identifier
17659060
Citation
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. doi: 10.1111/j.1399-5448.2007.00246.x.
Results Reference
background

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

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