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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	1 Month - 6 Months
Gender	All

More Inclusion & Exclusion Criteria

Arm 1: BPD±PH:

Inclusion Criteria:

- Born ≤ 30 weeks at birth.

- Post-menstrual age (PMA) ≥ 34 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.

- Informed written consent (parents/substitute decision maker)
Exclusion Criteria:
- 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. Inclusion Criteria.

- Born ≤ 30 weeks at birth.

- Recovering from Stage IIIb NEC as per modified Bell's staging (pneumoperitoneum requiring surgery) - Tolerating 30 ml/kg/day of enteral feeds.

- On invasive or non-invasive ventilation (NIPPV/nCPAP) with RSS >2.0 for > 12hours/day for at least 48 hours, 10-14 days post surgery.

- Informed written consent (parents/substitute decision maker) - Considered medically stable by clinical team.

Exclusion Criteria:

- 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.

- Other condition significantly affecting pulmonary function independent of prematurity or NEC

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05636397
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	The Hospital for Sick Children
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Estelle Gauda, MD
Principal Investigator Affiliation	Division Head, Division of Neonatology
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Canada
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	BPD - Bronchopulmonary Dysplasia, Pulmonary Hypertension, NEC

Additional Details

Preterm infants are born with underdeveloped organs and immune systems, placing them at great risk for morbidity. They are more susceptible to inflammatory injury, particularly from conditions of prematurity mediated by inflammatory pathways such as bronchopulmonary dysplasia (BPD) and necrotizing enterocolitis (NEC). L-CIT, an amino acid, is the first intermediate in the urea cycle as well as a precursor to arginine and nitric oxide (NO), which promotes blood flow. It is made in the intestine and has been shown to exert vasoprotective and anti-inflammatory effects. BPD-PH and NEC are two specific inflammatory diseases of prematurity involving CIT, arginine or NO deficiencies. Evaluation of the safety and PK/PD of L-CIT supplementation for diseases involving CIT, arginine or NO deficiencies in preterm infants is important. Therefore, in this trial the investigator would like to evaluate the safety and pharmacokinetics/pharmacodynamics (PD) of L-CIT supplementation in preterm infants post surgical NEC and BPD-PH.

Arms & Interventions

Arms

Experimental: BPD±PH

Arm 1: BPD±PH Total of 12-24 infants; 6-12 at each dose level of oral dosage form of L-Citrulline. (300 or 500 mg/kg/day divided q6 hours). Dose Level 1 = 300 mg/kg/day Dose Level 2 = 500 mg/kg/day

Experimental: Surgical NEC

Arm 2: sNEC A total of 18-36 infants with Stage III NEC; 6-12 at each dose level of oral dosage form of L-Citrulline. (75, 150 or 225 mg/kg/day divided q6 hours) Dose Level 1 = 75 mg/kg/day Dose Level 2 = 150 mg/kg/day Dose Level 3 = 225 mg/kg/day

Interventions

Dietary Supplement: - L-Citrulline

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).

Contact a Trial Team

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