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

Официальное название

A Phase I, Safety and Pharmacokinetics/Pharmacodynamics Study of Oral L-CIT Supplementation in Preterm Infants With BPD±PH and NEC

Обзор

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.

Подробное описание

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.

Вмешательства

• Пищевая добавка 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).

Первичные конечные точки

• Safety of oral L-Citrulline administration [Срок оценки: 5 years]

Вторичные конечные точки (12)

• Association of blood pressure as one of the PD outcomes with maximum L-CIT concentration (Cmax) [Срок оценки: 5 years]
• Association of stoma or nasogastric output as one of the PD outcomes with maximum L-CIT concentration (Cmax) [Срок оценки: 5 years]
• Association of stool output as one of the PD outcomes with maximum L-CIT concentration (Cmax) [Срок оценки: 5 years]
• Association of blood pressure with the area under the concentration time curve (AUC) for L-CIT [Срок оценки: 5 years]
• Association of stoma or nasogastric output with the area under the concentration time curve (AUC) for L-CIT [Срок оценки: 5 years]
• Association of stool output with the area under the concentration time curve (AUC) for L-CIT [Срок оценки: 5 years]
• Association of blood pressure with minimum L-CIT concentration (Cmin) [Срок оценки: 5 years]
• Association of stoma or nasogastric output with minimum L-CIT concentration (Cmin) [Срок оценки: 5 years]
• Association of stool output with minimum L-CIT concentration (Cmin) [Срок оценки: 5 years]
• Correlation between CIT and arginine levels [Срок оценки: 5 years]
• Biomarkers of inflammation [Срок оценки: 5 years]
• Oxidative stress [Срок оценки: 5 years]

Критерии участия

Arm 1: BPD±PH:

Критерии включения

• 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)

Критерии исключения

• 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

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Канада · 1 центр

• The Hospital For Sick Children — Toronto

Идентификаторы

NCT: NCT05636397 · 1000077413

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗