Official Title: “Reduction of Nocturnal Hypertension in Pediatric Renal Transplant Recipients”

The proposed study will investigate the effect of chronotherapeutic alteration of anti-hypertensive medication on nocturnal hypertension and end-organ injury in pediatric renal transplant recipients who are non-dippers. Additionally, the investigators aim to examine the association between response to intervention, serum adiponectin levels and adiponectin gene polymorphisms. The investigators hypothesize that (1) evening administration of anti-hypertensive medication will convert subjects from non-dipper to dipper status, improve mean nocturnal blood pressure (BP), and improve nocturnal BP load, (2) evening administration of anti-hypertensive medication will reduce albuminuria, left ventricular mass index (LVMI), rate of decline of glomerular filtration rate (eGFR) and will decrease pulse wave velocity (PWV), and (3) lower adiponectin levels and presence of adiponectin gene polymorphisms will be associated with less of a response to the intervention.

Study Type: Interventional

Study Design: Prevention, Randomized, Open Label, Parallel Assignment, Efficacy Study

Study Primary Completion Date: November 2011

Intervention(s) in this Clinical Trial

• Drug: Time change
  • Subject will move one of his/her current anti-hypertensive medications to 8 pm. ACEI will be moved preferentially if the subject is on two or more medications. If the subject is not on an ACEI, the choice of movement of medications will be as follows: ARB, calcium channel blockers, beta blockers and then alpha blockers. 1 BP med taken in the morning.Will move medication to 8pm.2 BP meds both taken in the morning.Will move one of the medications to 8pm. 2 BP meds, one in the morning,one in the evening. Will move the morning medication to 8pm.≥3 BP meds,at least one taken in the morning.Will move one of the medications to 8pm.
• Drug: Enalapril, Isradapine, Propranolol
  • Enalapril will be added in the evening at 8 pm. If the subject is already on an ACEI or there is a contraindication to starting an ACEI the subject will be started on isradipine instead. If the subject is already on an ACEI and calcium channel blocker at baseline, propranolol will then be the new medication added. Dosing will be as follows: ACEI: Enalapril < 40 kg starting dose 2.5 mg titrate to 5 mg > 40 kg starting dose 5 mg titrate to 10mg Calcium Channel Blocker: Isradipine < 40 kg 2.5 mg > 40 kg starting dose 2.5 mg titrate to 5 mg Beta Blocker: Propranolol <40 kg starting dose 10 mg titrate to 20 mg >40 kg starting dose 20 mg titrate to 40 mg

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Medication Time Change
  • Subject will move one of his/her current anti-hypertensive medications to 8 pm.
• Active Comparator: New Medication
  • A new anti-hypertensive medication will be added at 8pm.
• No Intervention: Control
  • Subjects in the control group will continue to take their medications as usual.

Primary Measures

• Proportion of subjects in each of the treatment arms who change from non-dipper to dipper status
  • Time Frame: 3 months and 6 months
    Safety Issue?: No

Secondary Measures

• Change in night-time systolic/diastolic blood pressure
  • Time Frame: 3 months and 6 months
    Safety Issue?: No
• Change in left ventricular mass index
  • Time Frame: 3 months and 6 months
    Safety Issue?: No
• Change in albumin:creatinine ratio
  • Time Frame: 3 months and 6 months
    Safety Issue?: No
• Change in estimated glomerular filtration rate
  • Time Frame: 3 months and 6 months
    Safety Issue?: No
• Change in pulse wave velocity
  • Time Frame: 3 months and 6 months
    Safety Issue?: No
• Association of serum adiponectin levels and SNPs of adiponectin with outcomes
  • Time Frame: 3 months and 6 months
    Safety Issue?: No

Inclusion Criteria:

• Subjects age 5-21 years
• Stable kidney transplant recipients (<30% change in eGFR in past 3 months)
• eGFR > 30 ml/min/1.73 m2
• >6 months since kidney transplant
• ABPM: Non-dipper status defined as <10% decline in systolic or diastolic blood pressure from daytime to night-time

Exclusion Criteria:

• ABPM: Subjects with daytime mean blood pressure > 95% for height and sex
• Subjects on diuretic monotherapy will not be eligible for the time change group (to avoid discomfort of nocturnal enuresis)
• Subjects with nephrotic range proteinuria
• Subjects with major co-morbid conditions such as cardiac disease, pulmonary disease and diabetes mellitus
• Subjects/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures
• Subjects who are pregnant will not be eligible for the new medication group

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 5 Years

Maximum Age for this Clinical Trial: 21 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Shore Long Island Jewish Health System

Overall Clinical Trial Officials and Contacts

Christine B Sethna, MD, EdM Principal Investigator North Shore Long Island Jewish Health System  

Overall Contact: Christine B Sethna, MD, EdM 718-470-3423 csethna@nshs.edu

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01007994

Study ID Number: 09-054

ClinicalTrials.gov Identifier: NCT01007994

Health Authority: United States: Institutional Review Board