Half-life of Plasma Phytosterols in Very Low Birth Weight Preterm Infants With Parenteral Nutrition-associated Cholestasis

NCT02947594 | Completed

• 1 other identifier: DG469
• Study Type: observational
• Target: 37
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Liver Disease

Outcome Measures

Primary Outcomes (1)

• Change of plasma phytosterol concentrations in preterm infants during parenteral nutrition and after only intravenous lipid stopping

  Plasma campesterol, stigmasterol and sitosterol concentrations will be measured at 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 and 84 days from PN started. Plasma phytosterol concentrations will be measured by gas chromatography-mass spectrometry. Calibration curves will be used to calculate the phytosterol plasma concentrations (mg/L).

  7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 and 84 days

Secondary Outcomes (2)

• Liver dysfunction in preterm infants will be defined by conjugated bilirubin values from blood samples over 1 mg/dl

  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.

• Plasma phytosterols half-lives

  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

Eligibility Criteria

• Age: 24 Weeks - 32 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Preterm infants (24 \< gestational age \< 32 weeks; 500 g ≤ birth weight \< 1250 g) with parenteral nutrition-associated cholestasis.

You may qualify if:

• weeks \< gestational age \< 32 weeks;
• 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;

You may not qualify if:

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

Sponsors & Collaborators

• Università Politecnica delle Marche: lead

Related Publications (9)

• Zaloga GP. Phytosterols, Lipid Administration, and Liver Disease During Parenteral Nutrition. JPEN J Parenter Enteral Nutr. 2015 Sep;39(1 Suppl):39S-60S. doi: 10.1177/0148607115595978. Epub 2015 Jul 15.

  PMID: 26177665 BACKGROUND

• Savini S, D'Ascenzo R, Biagetti C, Serpentini G, Pompilio A, Bartoli A, Cogo PE, Carnielli VP. The effect of 5 intravenous lipid emulsions on plasma phytosterols in preterm infants receiving parenteral nutrition: a randomized clinical trial. Am J Clin Nutr. 2013 Aug;98(2):312-8. doi: 10.3945/ajcn.112.056556. Epub 2013 Jun 12.

  PMID: 23761482 BACKGROUND

• 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.

  PMID: 25897540 BACKGROUND

• El Kasmi KC, Anderson AL, Devereaux MW, Vue PM, Zhang W, Setchell KD, Karpen SJ, Sokol RJ. Phytosterols promote liver injury and Kupffer cell activation in parenteral nutrition-associated liver disease. Sci Transl Med. 2013 Oct 9;5(206):206ra137. doi: 10.1126/scitranslmed.3006898.

  PMID: 24107776 BACKGROUND

• Weingartner O, Teupser D, Patel SB. The Atherogenicity of Plant Sterols: The Evidence from Genetics to Clinical Trials. J AOAC Int. 2015 May-Jun;98(3):742-749. doi: 10.5740/jaoacint.SGEWeingartner. Epub 2015 May 19.

  PMID: 25942705 BACKGROUND

• 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.

  PMID: 1911714 BACKGROUND

• 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.

  PMID: 6827984 BACKGROUND

• 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.

  PMID: 1576118 BACKGROUND

• Ellegard L, Sunesson A, Bosaeus I. High serum phytosterol levels in short bowel patients on parenteral nutrition support. Clin Nutr. 2005 Jun;24(3):415-20. doi: 10.1016/j.clnu.2005.01.001.

  PMID: 15896428 BACKGROUND

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Phd, Professor of Neonatal Pediatrics at Polytechnical University of Marche (Ancona, Italy)

Study Record Dates

• First Submitted: September 6, 2016
• First Posted: October 28, 2016
• Study Start: January 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: February 1, 2017
• Last Updated: January 24, 2018

Record last verified: 2018-01