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Chronotherapy for Pediatric Chronic Kidney Disease

CB
Overseen ByChristine Bakhoum, MD, MAS
Age: < 65
Sex: Any
Trial Phase: Academic
Sponsor: Yale University
Must be taking: Antihypertensives
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 6 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether taking blood pressure medication at night, rather than in the morning, can better manage blood pressure in children and teens with chronic kidney disease. It targets those on a stable dose of blood pressure medication for at least three months and diagnosed with high blood pressure that does not decrease at night as expected. Participants will initially maintain their usual routine, then switch to taking their medication at night to assess any differences. As an unphased trial, this study provides participants the chance to contribute to valuable research that could enhance treatment strategies for young patients with chronic kidney disease.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you have been on a stable dose of anti-hypertensive medication for at least 3 months. If you are currently taking diuretic medications, you cannot participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking at least one blood pressure medication at bedtime, rather than in the morning, can safely help control blood pressure. Studies suggest that this timing can also reduce the risk of heart problems, such as heart attacks, in people with chronic kidney disease (CKD) and high blood pressure.

In some cases, taking medication at night helped most patients return to normal blood pressure patterns. One small study found that taking these medications in the evening significantly lowered heart-related issues for people with CKD.

These findings suggest that changing the timing of medication, without altering the medication itself, is generally safe for patients. This approach builds on treatments already used in various ways.12345

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a novel approach to managing pediatric chronic kidney disease through chronotherapy, which involves retiming the administration of anti-hypertensive drugs. Unlike traditional treatments that focus on the type or dosage of medication, this approach investigates the timing of drug delivery, specifically nighttime dosing. This could potentially improve blood pressure control by aligning medication administration with the body's natural rhythms, leading to more effective management of the condition with possibly fewer side effects. By comparing the current regimen to nighttime dosing, researchers hope to discover whether timing plays a crucial role in enhancing treatment outcomes for young patients.

What evidence suggests that re-timing of anti-hypertensive medication might be an effective treatment for pediatric chronic kidney disease?

Research has shown that taking blood pressure medication at night can be more effective than taking it in the morning. In this trial, one group of participants will continue with their current regimen, while another group will switch to nighttime dosing of one anti-hypertensive medication. Studies have found that evening dosing significantly lowers blood pressure during the night, which is especially beneficial for people with chronic kidney disease. For instance, one study found that taking medication at night reduced the systolic blood pressure by an average of 7 mm Hg at night, without affecting daytime blood pressure. Another study demonstrated that this approach helps maintain normal blood pressure patterns over 24 hours. These findings suggest that evening dosing could lead to better blood pressure control.678910

Who Is on the Research Team?

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Christine Bakhoum

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for children and adolescents up to 18 years old with chronic kidney disease (CKD) and high blood pressure, who have been on a stable dose of anti-hypertensive medication for at least three months. They must show abnormal blood pressure patterns overnight and have an eGFR between 30-90 ml/min/1.73 m2. Kids under six or those unable to complete necessary tests, on diuretics, with a history of organ transplant, cancer, or dialysis are excluded.

Inclusion Criteria

I am under 18 and have chronic kidney disease.
Your blood pressure does not decrease during sleep, as shown by a special test called ABPM.
I have been on the same blood pressure medication for at least 3 months.
See 1 more

Exclusion Criteria

I have had an organ transplant, cancer, or been on dialysis.
I am older than 6 years.
I am currently taking water pills.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either remain on their current regimen or switch to nighttime dosing of one anti-hypertensive medication. ABPM is obtained after 1 week and at 1 month.

1 month
2 visits (in-person)

Washout

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.

2 weeks
1 visit (in-person)

Crossover Treatment

Participants crossover to the opposite arm and an ABPM is obtained after 1 week and at 1 month.

1 month
2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Current regimen
  • Re-timing of anti-hypertensive drug
Trial Overview The study is testing if changing the time when one anti-hypertensive drug is taken from morning to evening can help normalize blood pressure during sleep in kids with CKD. It's a pilot crossover trial meaning each participant will receive both treatments in sequence over different periods.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: nighttime dosing of one anti-hypertensive medicationExperimental Treatment1 Intervention
Group II: remain on their current regimenActive Control1 Intervention

Re-timing of anti-hypertensive drug is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

🇪🇺
Approved in European Union as Antihypertensive agents for:
🇺🇸
Approved in United States as Blood pressure medications for:
🇨🇦
Approved in Canada as Antihypertensive agents for:
🇯🇵
Approved in Japan as Antihypertensive agents for:
🇨🇳
Approved in China as Antihypertensive agents for:
🇨🇭
Approved in Switzerland as Antihypertensive agents for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials
1,963
Recruited
3,046,000+

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

Collaborator

Trials
2,513
Recruited
4,366,000+

American Heart Association

Collaborator

Trials
352
Recruited
6,196,000+

Published Research Related to This Trial

In a study of 32 children with end-stage renal failure and chronic hypertension, 84.62% of those on chronic hemodialysis exhibited a blunted circadian blood pressure rhythm, indicating potential risks for end-organ damage.
Blood pressure measurements taken before and after dialysis were found to be reliable indicators of average blood pressure between dialysis sessions, correlating strongly with left ventricular mass index, which is important for assessing heart health in these patients.
[Continuous blood pressure monitoring over a 24-hour period in children with terminal renal failure treated with hemodialysis].Pejcić, I., Peco-Antić, A., Parezanović, V., et al.[2009]
A study of 851 children with chronic kidney disease (CKD) showed no significant improvement in casual blood pressure control between two time periods (2005-2008 and 2010-2013), indicating ongoing challenges in managing hypertension in this population.
However, the analysis revealed a concerning increase in masked hypertension and higher average sleep blood pressure indices in the later period, highlighting the need for better recognition and treatment of hypertension in children with CKD.
Is Blood Pressure Improving in Children With Chronic Kidney Disease? A Period Analysis.Barletta, GM., Pierce, C., Mitsnefes, M., et al.[2019]
In a study of 59 pediatric dialysis patients, antihypertensive treatment showed little change over the past decade, with 50% of patients using ACE inhibitors and 67.5% using amlodipine, but only 45% achieved satisfactory blood pressure control.
Despite the availability of various antihypertensive medications, the overall effectiveness of treatment in managing hypertension in pediatric dialyzed patients remains unsatisfactory, indicating a need for improved strategies.
Antihypertensive treatment prescription in pediatric dialysis patients in Poland: A comparison between two nationwide studies 2003/2004-2013.Wróblewski, K., Hincz, K., Miklaszewska, M., et al.[2018]

Citations

Nighttime Dosing - NIH RePORTERThis study will involve conducting a simple and practical clinical trial to determine if taking medication for high blood pressure at night, as opposed to in ...
Lowering Nighttime Blood Pressure With Bedtime Dosing ...The focus of this article is to describe the results and implications of the Hygia trial in the context of physiological evidence and previously ...
Morning vs Bedtime Dosing and Nocturnal Blood Pressure ...Studies have shown that evening dosing of antihypertensive drugs can be more effective than morning dosing in lowering 24-hour BP, normalizing ...
versus morning- dosing drug therapy for chronic kidney ... - NCBICompared with a morning dosing regimen, taking antihypertensive drug in the evening significantly lowered nighttime systolic blood pressure (SBP) (P<0.0001) and ...
Should Reducing Nocturnal Blood Pressure Be a ...Nocturnal BP was lowered by an average of 7 mm Hg without an increase in daytime BP; somewhat surprising is the observation that office BP was also lower after ...
Bedtime Dosing of Antihypertensive Medications Reduces ...In conclusion, among patients with CKD and hypertension, taking at least one antihypertensive medication at bedtime improves control of BP and reduces the risk ...
Efficacy and Safety of Nighttime Dosing of AntihypertensivesOne small study and 2 substudies of diabetes and chronic kidney disease suggest that bedtime dosing of ≥1 antihypertensives significantly reduced CV events. A ...
Cardiovascular outcomes in adults with hypertension ...Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in ...
Controversies in HypertensionThe focus of this article is to describe the results and implications of the Hygia trial in the context of physiological evidence and previously pub- lished and ...
An 8-Week Uncontrolled Trial | Request PDFAfter the drug shift, the night-day ratio of mean ABP decreased in 93.7% of patients, with normal circadian rhythm restored in 87.5%. The ...
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