Clinical trial NCT02947594: Half-life of Plasma Phytosterols in Very Low Birth Weight Preterm Infants With Parenteral Nutrition-associated Cholestasis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Disease
Lead sponsor: Università Politecnica delle Marche
Sponsor class: OTHER
First posted: 2016-10-28
Enrollment: 37
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 \< gestational age \< 32 weeks; 500 g ≤ birth weight \< 1250 g) with parenteral nutrition-associated cholestasis.

Brief summary: Parenteral nutrition-associated cholestasis (PNAC) is one of the most common complications resulting from administration of parenteral nutrition in neonates. Excess intravenous intake of vegetable oil-based lipid emulsions containing phytosterols is felt to be a major contributing factor. To date, no information is available on plasma phytosterols half-lives in very-low-birth-weight (VLBW) preterm infants with PNAC. In a prospective cohort study, plasma phytosterols (campesterol, stigmasterol and sitosterol) of VLBW preterm infants with PNAC will be measured by gas chromatography-mass spectrometry (GC-MS) during PN administration and also after the stop of intravenous lipid infusion. Plasma phytosterols half-lives will be calculated from the monoexponential decay curves. Blood samples will be weekly collected from 1st to 12th 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 vegetable oil-based lipid emulsions from the first hours of life;
* diagnosis of cholestasis during vegetable oil-lipid infusion (plasma conjugated bilirubin value \> 1 mg/dl)
* parental consent;

Exclusion Criteria:

* severe malformations;
* inborn errors of metabolism;
* severe congenital sepsis;
* normal liver functions (plasma conjugated bilirubin under 1 mg/dl during vegetable oil-lipid infusion).

Primary outcomes:
measure: Change of plasma phytosterol concentrations in preterm infants during parenteral nutrition and after only intravenous lipid stopping
timeFrame: 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 and 84 days
Secondary outcomes:
measure: Liver dysfunction in preterm infants will be defined by conjugated bilirubin values from blood samples over 1 mg/dl
timeFrame: Routinely checked at 7 and 42 days of life. Additional measure of conjugated bilirubin will be performed after 15 days if the value continues to be higher than 1 mg/dl.
measure: Plasma phytosterols half-lives
timeFrame: We will able to measure the plasma phytosterol half-lives (days) after the analysis of 3 or more blood samples collected from the stop of lipid infusion to 84 days of life
Other outcomes:
Locations:
Study officials:
References:
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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.
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