Chronotherapy in Children With Chronic Kidney Disease

Yale University

Status: Withdrawn

Conditions: Hypertension; Chronic Kidney Diseases

Treatments: Other: Re-timing of anti-hypertensive drug; Other: Current regimen

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05353335

2000031575

1K23DK129836-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 6 to 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

nighttime dosing of one anti-hypertensive medication

Experimental group

Description:

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.

Treatment:

Other: Re-timing of anti-hypertensive drug

remain on their current regimen

Active Comparator group

Description:

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.

Treatment:

Other: Current regimen