Caffeine Citrate for Newborn Brain Injury

No longer recruiting at 1 trial location

Overseen By Jenny Rumpel, MD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Arkansas

Must not be taking: Theophylline, Aminophylline, Caffeine

Disqualifiers: Genetic conditions, Status epilepticus, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether caffeine citrate can protect the kidneys of newborns with hypoxic ischemic encephalopathy, a condition where the brain lacks sufficient oxygen. The study will assess the safety and tolerability of different caffeine citrate doses when given with therapeutic cooling treatment. Newborns at least 35 weeks old undergoing whole-body cooling for brain injury may qualify for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potentially beneficial treatment.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications, but newborns who have been exposed to theophylline, aminophylline, or caffeine before enrollment cannot participate.

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

Research shows that caffeine citrate is generally safe for newborns and serves as a promising treatment for premature babies with breathing difficulties. Studies have found that caffeine may protect the brain and improve outcomes, such as reducing the risk of cerebral palsy and learning delays.

Despite its widespread use, monitoring for side effects remains important. In previous cases, babies receiving caffeine underwent close monitoring to ensure safety. This trial explores different doses to find the best balance between benefits and potential risks. Overall, caffeine citrate has a strong track record in newborns, suggesting it is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using caffeine citrate for newborn brain injury because it offers a unique approach compared to standard treatments. Unlike typical interventions, which may focus on managing symptoms or preventing further injury, caffeine citrate directly targets the brain's receptors to enhance alertness and improve neurological outcomes. The treatment is administered intravenously in varying doses tailored to the neonate's needs, offering flexibility and precision. Additionally, caffeine citrate is well-known for its safety profile in neonatal care, making it a promising candidate for reducing brain injury risks right from the first day of life.

What evidence suggests that this trial's treatments could be effective for newborn brain injury?

Research has shown that caffeine citrate can help protect the brains of infants with hypoxic ischemic encephalopathy (HIE). One study found that caffeine reduced brain damage in these infants, suggesting it may support healthy brain development. In premature infants, caffeine is already known to improve brain growth and function, especially in those with low birth weight. Previous trials have demonstrated that caffeine treatment can lower the risk of cerebral palsy and learning delays. These findings strongly support using caffeine citrate to promote brain health in newborns. In this trial, participants will receive different doses of caffeine citrate to evaluate its effectiveness at varying levels. ^{1 2 3 4 6}

Who Is on the Research Team?

Jennifer Rumpel, MD

Principal Investigator

University of Arkansas

Are You a Good Fit for This Trial?

This trial is for newborns at least 35 weeks old with hypoxic ischemic encephalopathy, undergoing cooling therapy to treat brain injury caused by oxygen deprivation. Babies can't join if they have genetic conditions affecting the kidneys, severe ongoing seizures, or prior exposure to similar drugs like theophylline.

Inclusion Criteria

I am undergoing cooling treatment for brain injury due to lack of oxygen at birth.

My newborn was admitted to the NICU within 24 hours of birth and was at least 35 weeks gestational age.

Exclusion Criteria

I have a genetic condition that affects my kidney function.

I have not taken theophylline, aminophylline, or caffeine before joining.

I have had a very long seizure or needed many medicines to control my seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Neonates receive a single dose of caffeine citrate within the first 24 hours of life, with varying doses based on the study arm

1 day

1 visit (in-person)

Monitoring

Blood and urine samples are collected to monitor caffeine levels, kidney function, and seizure activity

2 weeks

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on seizure incidence and kidney function

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Caffeine Citrate

Trial Overview The study tests how safe caffeine citrate is for these babies and how their bodies handle the drug. It's a first step in exploring whether caffeine can protect their kidneys during this critical time.

How Is the Trial Designed?

Group I: Arm 2: Medium dose caffeine Active Control 1 Intervention

Each neonate will receive a single dose of caffeine citrate in the first 24 hours of life. Arm 2 neonates will receive medium dose intravenous caffeine citrate (15 mg/kg).

Group II: Arm 3: High dose caffeine Active Control 1 Intervention

Each neonate will receive a single dose of caffeine citrate in the first 24 hours of life. Arm 3 neonates will receive high dose intravenous caffeine citrate (25 mg/kg).

Group III: Arm 1: Low dose caffeine Active Control 1 Intervention

Each neonate will receive a single dose of caffeine citrate in the first 24 hours of life. Arm 1 neonates will receive low dose intravenous caffeine citrate (5 mg/kg).

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Published Research Related to This Trial

A study of 566 preterm infants showed that a high maintenance dose of caffeine citrate (10 mg/kg per day) significantly reduced the need for high-concentration oxygen and the duration of oxygen therapy compared to a low dose (5 mg/kg per day).

While the high-dose group experienced benefits in respiratory support and reduced incidence of apnea and bronchopulmonary dysplasia, it also had a higher rate of feeding intolerance, indicating a need for further research on this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study. Yang, Y., Lu, KY., Cheng, R., et al.[2022]

A population pharmacokinetic (PPK) model for caffeine citrate was developed using data from 46 preterm infants, providing a tailored approach for treating apnea of prematurity in this population.

The model identified weight and post-natal age as key factors influencing caffeine clearance and distribution, which can help optimize individualized treatment for Chinese premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic study of caffeine citrate in Chinese premature infants with apnea. Guo, A., Zhu, Z., Xue, J., et al.[2022]

Citations

1. nature.com nature.com/articles/s41390-025-04387-1

Cumulative caffeine exposure predicts ... Preterm infants who receive caffeine for apnea of prematurity have improved neurodevelopmental outcomes compared to untreated infants.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8517339/

Encephalopathy in Preterm Infants - PubMed Central - NIH For premature infants with birth weight ≤1,250 g, early administration of caffeine citrate can improve and correct the microstructure of white ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10869636/

A phase I trial of caffeine to evaluate safety in infants with ... A promising, safe, and commonly used drug, caffeine, may reduce hypoxic injury to the brain and thus offer neuroprotection for infants with HIE.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06972849

NCT06972849 | Caffeine Citrate to Improve Neonatal ... The goal of this clinical trial to learn what dose/s of caffeine citrate works to treat preterm born babies who have episodes where they stop breathing.

5. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.124.048264

Perinatal Caffeine Administration Improves Outcomes in an ... The Caffeine for Apnea of Prematurity trial demonstrated reduced risks of cerebral palsy and cognitive delay at 18 months with a daily treatment ...

6. withpower.com withpower.com/trial/phase-1-hypoxia-ischemia-brain-3-2022-c6a81

Caffeine Citrate for Newborn Brain Injury This suggests that caffeine citrate is generally safe for use in newborns, though monitoring for side effects is important. Show more.