Safety and PK-PD Study of Oral L-CIT in Preterm Infants With BPD±PH and NEC
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: L-Citrulline.
- Who it may be relevant to
- Registry conditions: BPD - Bronchopulmonary Dysplasia, Pulmonary Hypertension, NEC. Basic parameters: 1 months — 6 months · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase I, Safety and Pharmacokinetics/Pharmacodynamics Study of Oral L-CIT Supplementation in Preterm Infants With BPD±PH and NEC
Overview
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.
Detailed description
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.
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).
Primary outcome measures
- Safety of oral L-Citrulline administration [Time frame: 5 years]
Secondary outcome measures (12)
- Association of blood pressure as one of the PD outcomes with maximum L-CIT concentration (Cmax) [Time frame: 5 years]
- Association of stoma or nasogastric output as one of the PD outcomes with maximum L-CIT concentration (Cmax) [Time frame: 5 years]
- Association of stool output as one of the PD outcomes with maximum L-CIT concentration (Cmax) [Time frame: 5 years]
- Association of blood pressure with the area under the concentration time curve (AUC) for L-CIT [Time frame: 5 years]
- Association of stoma or nasogastric output with the area under the concentration time curve (AUC) for L-CIT [Time frame: 5 years]
- Association of stool output with the area under the concentration time curve (AUC) for L-CIT [Time frame: 5 years]
- Association of blood pressure with minimum L-CIT concentration (Cmin) [Time frame: 5 years]
- Association of stoma or nasogastric output with minimum L-CIT concentration (Cmin) [Time frame: 5 years]
- Association of stool output with minimum L-CIT concentration (Cmin) [Time frame: 5 years]
- Correlation between CIT and arginine levels [Time frame: 5 years]
- Biomarkers of inflammation [Time frame: 5 years]
- Oxidative stress [Time frame: 5 years]
Eligibility criteria
Arm 1: BPD±PH:
Inclusion criteria
- 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)
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 50 ml/kg/day of enteral feeds
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Other
Study locations
Canada · 1 center
- The Hospital For Sick Children — Toronto
Identifiers
NCT: NCT05636397 · 1000077413