Enteral L Citrulline Supplementation in Preterm Infants - Safety, Efficacy and Dosing
Condition: Bronchopulmonary Dysplasia; Bronchopulmonary Dysplasia Associated Pulmonary Hypertension; Pulmonary Hypertension; Premature Birth; Chronic Lung Disease of Prematurity
MeSH terms: Lung Diseases; Hypertension, Pulmonary; Bronchopulmonary Dysplasia; Premature Birth; Hypertension; Hyperplasia
Intervention: Enteral L-citrulline
Intervention description: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Previous studies in patients undergoing cardiac surgery have shown that post-operative pulmonary hypertension did not develop in patients with citrulline level > 37 micromol/L. A cross-sectional study reported that citrulline levels < 29 micromol/L was associated with BPD_PH (100% sensitivity and 75% specificity) hence this may be used as a screening tool for BPD_PH2. The investigators will use the higher levels of citrulline of the reported levels as our goal (>37µmol/L). The investigators will supplement infants with 3 different dosages and check serum levels to see what dose is required to achieve the optimal plasma level of citrulline (>37µmol/L).
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Maximum age: 30 Weeks
Healthy volunteers: No
Keywords: Bronchopulmonary dysplasia; Pulmonary hypertension; Citrulline

Summary:

      Oral L-citrulline supplementation may prevent and/or decrease the severity of chronic lung
      disease associated with pulmonary hypertension in preterm infants. Since oral L-citrulline
      supplementation has never been studied in preterm infants before, the side effect profile and
      appropriate dosing are still unknown. In this pilot study, the investigators will determine
      the safety profile, efficacy and appropriate dosing of oral L-citrulline in preterm infants.
      In the future, information from this study will be utilized to conduct a randomized
      placebo-controlled trial to evaluate the role of L-citrulline supplementation in treating
      BPD_PH.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Infants less than or equal to 30 weeks' gestational age born at UTMB, Galveston.

          -  Parents have provided informed consent/assent in a manner that is approved by the IRB

        Exclusion Criteria:

          -  Known congenital or chromosomal anomalies.

          -  Congenital heart disease affecting cardio-respiratory system (other than PDA, PFO or
             ASD)

          -  Necrotizing enterocolitis, sepsis, or any condition requiring surgery prior to
             recruitment