Safety and PK-PD Study of Oral L-CIT in Preterm Infants With BPD±PH and NEC

NCT05636397 | Recruiting DMC

• 1 other identifier: 1000077413
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and explore the PK/PD of L-CIT supplementation in preterm infants to prevent the development of inflammatory pathways initiated by low levels of plasma CIT, specifically in preterm infants with post-surgical NEC and BPD±PH.

Conditions

BPD - Bronchopulmonary Dysplasia; Pulmonary Hypertension; NEC

Keywords

BPD±PH; surgical NEC; L-Citrulline; Pharmacokinetic profile; Pharmacodynamic profile; Preterm neonates

Outcome Measures

Primary Outcomes (1)

• Safety of oral L-Citrulline administration

  The number of patients with adverse events (AE) as a measure of safety and tolerability

  5 years

Secondary Outcomes (22)

• Association of blood pressure as one of the PD outcomes with maximum L-CIT concentration (Cmax)

  5 years

• Association of stoma or nasogastric output as one of the PD outcomes with maximum L-CIT concentration (Cmax)

  5 years

• Association of stool output as one of the PD outcomes with maximum L-CIT concentration (Cmax)

  5 years

• Association of blood pressure with the area under the concentration time curve (AUC) for L-CIT

  5 years

• Association of stoma or nasogastric output with the area under the concentration time curve (AUC) for L-CIT

  5 years

Study Arms (2)

BPD±PH

EXPERIMENTAL

Arm 1: BPD±PH Total of 18 infants at 300 mg/kg/day divided q6 hours

Dietary Supplement: L-Citrulline

Surgical NEC

EXPERIMENTAL

Arm 2: sNEC A total of 18 infants with Stage III NEC: Dose Level 1 = 150 mg/kg/day divided q6 hours for one week. If study participant tolerates 150mg/kg/day well, then escalate the same study participant to Dose 2 after 1 week of starting Citrulline. Dose Level 2 = 200 mg/kg/day divided q6 hours At 34 weeks of gestation, if baby is still on respiratory support of \>250ml/min of Low flow oxygen, then we will escalate to the dose of 300mg/kg/day and continue until 38 weeks PMA or until discharge, whichever is earlier.

Dietary Supplement: L-Citrulline

Interventions

L-Citrulline DIETARY_SUPPLEMENT

Citrulline is a nonessential amino acid made in the small intestine, occurs naturally in the body, and is believed to help reduce inflammation.L-CIT is a part of the urea cycle, produced as a by-product along with nitric oxide (NO).

BPD±PH; Surgical NEC

Eligibility Criteria

• Age: 1 Month - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Born ≤ 30 weeks at birth
• Post-menstrual age (PMA) ≥ 32 weeks
• Echocardiographic evidence of PH for infants with BPD+PH.
• On invasive or non-invasive ventilation with RSS \>2.0 for \>12hours/day for at least 48 hours as an early predictor of evolving BPD
• Informed written consent (parents/substitute decision maker)

You may not qualify if:

• Congenital Heart Disease \[Exceptions: small atrial septal defect (ASD), small ventricular septal defect (VSD), small patent ductus arteriosus (PDA)\]
• Infants with pulmonary vein stenosis
• Concurrent sepsis with hemodynamic instability
• Infants considered likely to die within next 7 days
• Any other condition that, in the opinion of the investigator, may adversely affect the infant's ability to complete the study or its measures or pose significant risk to the infant
• Arm 2: surgical NEC
• Born ≤ 30 weeks at birth
• Recovering from Stage IIIb NEC as per modified Bell's staging (pneumoperitoneum requiring surgery)
• Tolerating 50 ml/kg/day of enteral feeds
• Informed written consent (parents/substitute decision maker)
• Considered medically stable by clinical team
• Congenital heart disease (except small ASD, small VSD and non hsPDA)
• Pulmonary vein stenosis
• Concurrent sepsis with hemodynamic instability
• Likely to die within next 7 days

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (1)

The Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Hypertension, Pulmonary

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Estelle Gauda, MD

  Division Head, Division of Neonatology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachana Patel, MSc, CCRP

CONTACT

+1(416)-813-7654; rachana.patel@sickkids.ca

Jeffrey Antwi

CONTACT

+1(416-)813-7654; jeffrey.antwi@sickkids.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Division of Neonatology

Model Details: This is a prospective dose-escalation study. Arm 1: BPD-PH Total of 18 infants at 300 mg/kg/day divided q6 hours Arm 2: sNEC A total of 18 infants with Stage III NEC: Dose Level 1 = 150 mg/kg/day divided q6 hours for one week. If study participant tolerates 150mg/kg/day well, then escalate the same study participant to Dose 2 after 1 week of starting Citrulline. Dose Level 2 = 200 mg/kg/day divided q6 hours At 34 weeks of gestation, if baby is still on respiratory support of \>250ml/min of Low flow oxygen, then we will escalate to the dose of 300mg/kg/day and continue until 38 weeks PMA or until discharge, whichever is earlier.

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: December 5, 2022
• Study Start: November 1, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)