Type 1 DiabetesPhase 3PREVENTKDNCT00729365

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

A Phase 3 study testing Ramipril in people with Type 1 Diabetes, run by Northwestern University at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 13 to 50 years
Conditions the study is for: Type 1 Diabetes
What is being tested?: Ramipril
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 65 participants
Where: 6 sitesUnited States
Study dates: Jul 2008to Jun 2010
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 13 to 50 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

Who cannot join

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

Show all 12Show fewer

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.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Rush University Medical Center, Endocrinology Section
Chicago, Illinois, 60612
University of Illinois at Chicago
Chicago, Illinois, 60612
University of Chicago
Chicago, Illinois, 60637
University of Florida
Gainesville, Florida, 32611
Loyola University Chicago
Maywood, Illinois, 60153

Other trials in United States

About this study

Official title: Nocturnal Hypertension and Prevention of Microalbuminuria in Type 1 Diabetes

Read the 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
Being tested: Ramipril, Placebo
Keywords: Urine albumin excretion rates, Nighttime and daytime blood pressure, Endothelial Dysfunction
Medical subject headings: Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RamiprilDrug
Also called ACE Inhibitor
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.
PlaceboDrug
Dippers (category of subjects with a nighttime dip in blood pressure) will all be given Placebo. Control group.
PlaceboDrug
Subjects with nighttime blood pressure that does not drop during the night ("non-dippers") maybe randomized into the control group and given Placebo.

Study groups in NCT00729365
Study group	Role	What they receive
Dippers - Placebo Treated	Placebo comparator	Subjects with normal nighttime blood pressure profile that decreases at night (Dippers). This group are all given placebo. Receives: Drug: Placebo
NonDippers - Placebo Treated	Placebo comparator	Subjects with nighttime blood pressure that does not drop during the night (non-dippers). This group will be given placebo. Receives: Drug: Placebo
NonDippers - Ramipril Treated	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). Receives: Drug: Ramipril

What is being measured

The primary outcome is the main question the study is designed to answer.

Development of Microalbuminuria (High Urine Albumin). Hypertension, Urine and Blood Markers Will Also be Evaluated for Assessment of Kidney Disease State.
Measured: at 3months and then every 6months during the 5years of the study

Secondary outcomes (1)

We Will Assess Changes in the Relative Stiffness of Your Arteries (Endothelial Dysfunction) in Persons With Type 1 Diabetes Over the 5year Study.
Measured: year 1, 3, 5 and after the washout phase (5years and 1month)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2008Jun 2010

First posted7 Aug 2008 (estimated)
Study startJul 2008
Primary completionJun 2010
Study completionJun 2010

Why it stopped: Data from other studies showed that study could not be completef successfully

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
More trials run by Northwestern UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 65 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00729365
Sponsor's protocol ID: 1U01DK071733-01A1
Other IDs: 1U01DK071733-01A1
Acronym: PREVENTKD
Status last verified: Feb 2015
First submitted: 4 Aug 2008
Last updated: 17 Mar 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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. doi: 10.1056/NEJMoa013410.
PubMed 12226150
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.
PubMed 15939805
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.
PubMed 8428785
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.
PubMed 17659060

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Type 1 Diabetes trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Nocturnal Hypertension and Prevention of Microalbuminuria in Type 1 Diabetes
ClinicalTrials.gov ID: NCT00729365
Acronym / sponsor ID: PREVENTKD / 1U01DK071733-01A1
Conditions: Type 1 Diabetes
Keywords: Urine albumin excretion rates, Nighttime and daytime blood pressure, Endothelial Dysfunction
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Data from other studies showed that study could not be completef successfully
Enrolment: 65 participants (actual)
Lead sponsor: Northwestern UniversityUniversity, hospital or other
Collaborators: Juvenile Diabetes Research Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study start: Jul 2008
Primary completion: Jun 2010 (actual)
Study completion: Jun 2010 (actual)
First posted: 7 Aug 2008 (estimated)
Results: Posted 9 Jan 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Dippers - Placebo Treated	Placebo comparator	Drug: PlaceboSubjects with normal nighttime blood pressure profile that decreases at night (Dippers). This group are all given placebo.
NonDippers - Placebo Treated	Placebo comparator	Drug: PlaceboSubjects with nighttime blood pressure that does not drop during the night (non-dippers). This group will be given placebo.
NonDippers - Ramipril Treated	Active comparator	Drug: RamiprilSubjects with nighttime blood pressure that does not drop during the night (non-dippers). This group will be given ACE inhibitor (study medication).

Who may qualify

Ages: 13 to 50 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RamiprilAlso: ACE InhibitorACE 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.	Drug	NonDippers - Ramipril Treated
PlaceboDippers (category of subjects with a nighttime dip in blood pressure) will all be given Placebo. Control group.	Drug	Dippers - Placebo Treated
PlaceboSubjects with nighttime blood pressure that does not drop during the night ("non-dippers") maybe randomized into the control group and given Placebo.	Drug	NonDippers - Placebo Treated

Primary outcome

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

1 secondary outcome

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)

Results and safety

Results posted to the registry on 9 Jan 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dippers - Placebo Group	33	0
Non-dippers - Placebo	6	0
Non-Dippers - Ramipril	7	0

Primary outcome: 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

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 1 year. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dippers - Placebo	0 of 0	0 of 0	Not reported
Non-Dippers - Placebo	0 of 0	0 of 0	Not reported
Non-Dippers - Ramipril	0 of 0	0 of 0	Not reported

Limitations and caveats (from the sponsor): The study was terminated prematurely because of new information from the literature from other studies showing that this study could not be successful. Only 59 patients were screened and consented and 46 were found acceptable who were randomized.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 12226150Lurbe 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.
Background: PubMed 15939805Dolan 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.
Background: PubMed 8428785Lurbe 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.
Background: PubMed 17659060Haller 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark E Molitch, MD principal investigator

Professor of Medicine

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ramipril in people with Type 1 Diabetes, run by Northwestern University at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00729365, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2015.