Clinical trial NCT02758834: Half-life of Plasma Phytosterols in Preterm Infants on Parenteral Nutrition
Official title: Half-life of Plasma Phytosterols in Very Low-birth-weight Preterm Infants on Routine Parenteral Nutrition With Soy-bean Oil Based Lipid Emulsions
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Diseases
Keywords: Preterm Infants
Phytosterols
Parenteral Nutrition
Lead sponsor: Università Politecnica delle Marche
Sponsor class: OTHER
First posted: 2016-05-03
Enrollment: 45
Sex: ALL
Minimum age (years): 24
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Preterm infants (24 weeks \< gestational age \< 32 weeks; 500 g ≤ birth weight \< 1250 g) who received intravenous soy oil-based lipid emulsions from the first hours of life.

Brief summary: The purpose of this study is to determine plasma phytosterols half-lives in preterm infants who received intravenous soy oil-based lipid emulsions.

Detailed description: Several studies reported the relationship between plasma phytosterol concentrations and parenteral nutrition-associated cholestasis (PNAC). Information on plasma phytosterols half-lives in very-low-birth-weight (VLBW) preterm infants on lipid parenteral nutrition (PN) are lacking. In a prospective cohort study, plasma phytosterols (campesterol, stigmasterol and sitosterol) of VLBW preterm infants on routine PN will be measured by gas chromatography-mass spectrometry (GC-MS) during PN administration and after only lipid stopping. Plasma phytosterols half-lives will be calculated from the monoexponential decay curves. Blood samples will be weekly collected from 1st to 7th week of life during routine metabolic tolerance analysis or gas-analysis in order to avoid burden of additional phlebotomy. Samples will be collected in ethylenediaminetetraacetic acid-tubes and immediately centrifugated. Plasma will be stored in pyrogallol added-tubes at -20°C until analysis. Saponification reaction will be done using 5-alpha-cholestane as internal standard.

Eligibility criteria: Inclusion Criteria:

* 24 weeks \< gestational age \< 32 weeks;
* 500 g ≤ birth weight \< 1250 g;
* parenteral nutrition with soy oil-based lipid emulsions from the first hours of life;
* parental consent.

Exclusion Criteria:

* length of parenteral nutrition \> 24 days;
* severe malformations;
* inborn errors of metabolism;
* severe congenital sepsis;
* liver dysfunctions.

Primary outcomes:
measure: Change of plasma phytosterol concentrations in preterm infants during parenteral nutrition and after only lipid stopping.
timeFrame: 7, 14, 21, 28, 35, 42 and 49 days
Secondary outcomes:
measure: Normal liver function of preterm infants will be define by conjugated bilirubin values from blood samples under 1 mg/dl.
timeFrame: 7 days and 42 days of life
measure: Plasma phytosterols half-lives
timeFrame: After the collection of 3 or more blood samples collected when the lipid infusion is stopped.
Other outcomes:
Locations:
Study officials:
affiliation: Università Politecnica delle Marche
name: Virgilio P. Carnielli, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nghiem-Rao TH, Tunc I, Mavis AM, Cao Y, Polzin EM, Firary MF, Wang X, Simpson PM, Patel SB. Kinetics of phytosterol metabolism in neonates receiving parenteral nutrition. Pediatr Res. 2015 Aug;78(2):181-9. doi: 10.1038/pr.2015.78. Epub 2015 Apr 21.
citation: Bhattacharyya AK, Connor WE, Lin DS, McMurry MM, Shulman RS. Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis. Arterioscler Thromb. 1991 Sep-Oct;11(5):1287-94. doi: 10.1161/01.atv.11.5.1287.
citation: Lin HJ, Wang C, Salen G, Lam KC, Chan TK. Sitosterol and cholesterol metabolism in a patient with coexisting phytosterolemia and cholestanolemia. Metabolism. 1983 Feb;32(2):126-33. doi: 10.1016/0026-0495(83)90216-0.
citation: Ostlund RE Jr, McGill JB, Zeng CM, Covey DF, Stearns J, Stenson WF, Spilburg CA. Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans. Am J Physiol Endocrinol Metab. 2002 Apr;282(4):E911-6. doi: 10.1152/ajpendo.00328.2001.
citation: Salen G, Tint GS, Shefer S, Shore V, Nguyen L. Increased sitosterol absorption is offset by rapid elimination to prevent accumulation in heterozygotes with sitosterolemia. Arterioscler Thromb. 1992 May;12(5):563-8. doi: 10.1161/01.atv.12.5.563.
citation: Pupillo D, Correani A, Biagetti C, D'Ascenzo R, Simonato M, Verlato G, Cogo P, Rocchi MBL, Carnielli VP. Half-life of plasma phytosterols in very low birth weight preterm infants on routine parenteral nutrition with vegetable oil-based lipid emulsions. Clin Nutr. 2018 Feb;37(1):262-269. doi: 10.1016/j.clnu.2016.12.022. Epub 2016 Dec 30.