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

NCT ID: NCT00729365

Last Updated: 2015-03-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2010-06-30

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.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Dippers - Placebo Treated

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Dippers (category of subjects with a nighttime dip in blood pressure) will all be given Placebo. Control group.

NonDippers - Placebo Treated

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects with nighttime blood pressure that does not drop during the night ("non-dippers") maybe randomized into the control group and given Placebo.

NonDippers - Ramipril Treated

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

Group Type: ACTIVE_COMPARATOR

Ramipril

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Placebo

Dippers (category of subjects with a nighttime dip in blood pressure) will all be given Placebo. Control group.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

ACE Inhibitor

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.

• 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.

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.

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

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

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Mark Molitch

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark E Molitch, MD

Role: PRINCIPAL_INVESTIGATOR

Professor of Medicine

Locations

University of Florida

Gainesville, Florida, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Rush University Medical Center, Endocrinology Section

Chicago, Illinois, United States

University of Illinois at Chicago

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Loyola University Chicago

Maywood, Illinois, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 12226150 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15939805 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8428785 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17659060 (View on PubMed)

Other Identifiers

1U01DK071733-01A1

Identifier Type: NIH

Identifier Source: secondary_id

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1U01DK071733-01A1

Identifier Type: NIH

Identifier Source: org_study_id

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