Chronotherapy in Children With Chronic Kidney Disease

Investigating if Nocturnal Blood Pressure Patterns Are Modifiable in Children With Chronic Kidney Disease

This is a pilot, crossover trial in which the investigator will determine if retiming of one anti-hypertensive medication from morning to evening can effectuate normal blood pressure dipping patterns in children and adolescents with chronic kidney disease.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Chronic Kidney Diseases
• Intervention / Treatment: Other: Re-timing of anti-hypertensive drug; Other: Current regimen

Detailed Description

Normally blood pressure declines by at least 10% from daytime to nighttime. In children with chronic kidney disease (CKD), often this does not happen (termed "non-dipping"). This study is a pilot, randomized cross-over trial. The main purpose of this study is to investigate whether non-dipping can be modified with retiming of anti-hypertensives in children with CKD. This is important because in adults, non-dipping has been associated with increased cardiovascular disease risk and more rapid progression of kidney disease. Thus, identification of how to modify this in children with CKD, may lead to future randomized controlled trials to evaluate whether chronotherapy improves outcomes in this population, which is at high risk for morbidity and mortality in adulthood.

The primary objective of this study is to determine whether retiming of one anti-hypertensive to the evening will increase nocturnal systolic blood pressure change (%) in children with CKD, hypertension and non-dipping.

The secondary objective of this study is to determine whether retiming of one anti-hypertensive to the evening will increase nocturnal diastolic blood pressure change (%) in children with CKD, hypertension and non-dipping. Another secondary objective is to determine if the proportion of subjects classified as having a non-dipping pattern is significantly lower on evening dosing of anti-hypertensives.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christine Bakhoum, MD, MAS; Phone Number: 2037376095; Email: christine.bakhoum@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale New Haven Children's Hospital/Yale New Haven Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female child/adolescent up to 18 years of age with CKD
• estimated glomerular filtration rate (eGFR) of 30 to 90 ml/min/1.73 m2
• diagnosed with hypertension and on a stable dose of anti-hypertensive medication(s) for at least 3 months
• Non-dipping identified on ABPM

Exclusion Criteria:

• history of organ transplantation, oncological disease, or dialysis
• inability to complete 24-hour ABPM or 24-hour urine collection
• Children less than 6 years of age will be excluded, as they often are unable to complete a successful ABPM study (≥ 40 readings, with 1 reading per hour of sleep)
• Currently on diuretic medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nighttime dosing of one anti-hypertensive medication; 13 participants will be randomized to nighttime dosing of one anti-hypertensive medication. After 1 week, a repeat ABPM will be obtained. At 1 month from randomization, another ABPM will be obtained. Following this, there will be a 2-week washout period, during which all subjects will be on their usual anti-hypertensive regimen. A repeat ABPM will be obtained after the washout period. Next, the subjects will crossover to the opposite arm and an ABPM will be obtained after 1 week. A final ABPM will be obtained at 1 month after crossover.	Other: Re-timing of anti-hypertensive drug; The intervention will consist of shifting the anti-hypertensive medication from morning/early dose to an evening/later dose
Active Comparator: remain on their current regimen; 13 participants will be randomized to remain on their current regimen. After 1 week, a repeat ABPM will be obtained. At 1 month from randomization, another ABPM will be obtained. Following this, there will be a 2-week washout period, during which all subjects will be on their usual anti-hypertensive regimen. A repeat ABPM will be obtained after the washout period. Next, the subjects will crossover to the opposite arm and an ABPM will be obtained after 1 week. A final ABPM will be obtained at 1 month after crossover.	Other: Current regimen; The participants will begin on their current regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in nocturnal systolic blood pressure in participants administered anti-hypertensive medications at night on Ambulatory blood pressure monitor(ing) (ABPM).	Percent change in systolic nocturnal blood pressure will be calculated as : (daytime mean SBP - nighttime mean SBP)/daytime mean SBP x 100 to assess if nocturnal BP dipping can be restored.	Baseline and Month 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in nocturnal diastolic blood pressure in participants administered anti-hypertensive medications at night on ABPM.	Percent change in systolic nocturnal blood pressure will be calculated as: (daytime mean DBP - nighttime mean DBP)/daytime mean DBP x 100 to assess if nocturnal BP dipping can be restored.	Baseline and Month 1
Change in proportion of participants with restoration of dipping while on the intervention, defined as <10% systolic or diastolic nocturnal blood pressure change	This outcome will assess if the proportion of subjects classified as having a non-dipping pattern is significantly lower on evening dosing of anti-hypertensives. Restoration of dipping would mean that both systolic and diastolic nocturnal blood pressure change are greater than or equal to 10%, after the intervention.	Baseline and Month 1

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); American Heart Association
• Investigators: Principal Investigator: Christine Bakhoum, Yale University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: April 25, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Antihypertensive Agents
• Other Study ID Numbers: 2000031575; 1K23DK129836-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No