Liver DiseaseNCT02947594
Half-life of Plasma Phytosterols in Very Low Birth Weight Preterm Infants With Parenteral Nutrition-associated Cholestasis
An observational study of Liver Disease, run by Università Politecnica delle Marche.
Trial 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. Read more about this study
- Who is it for?
- Ages 24 weeks to 32 months
- Conditions the study is for
- Liver Disease
- How many people
- 37 participants
- Where
- No sites listed yet
- Study dates
- Jan 2014to Feb 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 weeks to 32 months
- All sexes
- No healthy volunteers
- Child
Study population: Preterm infants (24 < gestational age < 32 weeks; 500 g ≤ birth weight < 1250 g) with parenteral nutrition-associated cholestasis.
Who may be able to join
- 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;
Who cannot join
- severe malformations;
- inborn errors of metabolism;
- severe congenital sepsis;
- normal liver functions (plasma conjugated bilirubin under 1 mg/dl during vegetable oil-lipid infusion).
About this study
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
- Medical subject headings
- Liver Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Eligibility of preterm infants will be related to liver function. Conjugated bilirubin value from blood sample is a good sign of hepatic function. The threshold value was defined to 1 mg/dl. Just preterm infants who will have conjugated bilirubin values more of 1 mg/dl will be included in the study. Conjugated bilirubin will be measured at 7 and 42 days of life on routine care. When the conjugated bilirubin value will be higher than 1 mg/dl, the analysis will be repeated every 15 days until it returns under the threshold value (1 mg/dl). Parenteral nutrition-associated cholestasis will be only diagnosed in patients with pathological values of conjugated bilirubin (over 1 mg/dl) during vegetable oil-lipid infusion.
Measured: 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
Plasma phytosterol half-lives (days) will be measured using 3 or more plasma phytosterol concentrations calculated after only lipid stopping. Half-life of plasma phytosterols will be calculated from monoexponential decay curves.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2016 (estimated)
- Study startJan 2014
- Primary completionAug 2016
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Università Politecnica delle Marche
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Virgilio Paolo Carnielli, Università Politecnica delle Marche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02947594
- Sponsor's protocol ID
- DG469
- Status last verified
- Jan 2018
- First submitted
- 6 Sep 2016
- Last updated
- 24 Jan 2018
- Results posted
- No
Publications
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.
PubMed 26177665Savini 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.
PubMed 23761482Nghiem-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.
PubMed 25897540El 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.
PubMed 24107776Weingartner 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.
PubMed 25942705Bhattacharyya 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.
PubMed 1911714Lin 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.
PubMed 6827984Salen 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.
PubMed 1576118Ellegard 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.
PubMed 15896428
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Half-life of Plasma Phytosterols in Very Low Birth Weight Preterm Infants With Parenteral Nutrition-associated Cholestasis
- ClinicalTrials.gov ID
- NCT02947594
- Acronym / sponsor ID
- DG469
- Conditions
- Liver Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Università Politecnica delle MarcheUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Aug 2016 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 28 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 24 weeks to 32 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Preterm infants (24 < gestational age < 32 weeks; 500 g ≤ birth weight < 1250 g) with parenteral nutrition-associated cholestasis.
Key inclusion criteria (5 listed)
- 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;
Key exclusion criteria (4 listed)
- severe malformations;
- inborn errors of metabolism;
- severe congenital sepsis;
- normal liver functions (plasma conjugated bilirubin under 1 mg/dl during vegetable oil-lipid infusion).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change of plasma phytosterol concentrations in preterm infants during parenteral nutrition and after only intravenous lipid stopping
Time frame: 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 and 84 days
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).
2 secondary outcomes
Liver dysfunction in preterm infants will be defined by conjugated bilirubin values from blood samples over 1 mg/dl
Time frame: 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
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2018.
- Background: PubMed 26177665Zaloga 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.
- Background: PubMed 23761482Savini 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.
- Background: PubMed 25897540Nghiem-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.
- Background: PubMed 24107776El 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.
- Background: PubMed 25942705Weingartner 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.
- Background: PubMed 1911714Bhattacharyya 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.
- Background: PubMed 6827984Lin 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.
- Background: PubMed 1576118Salen 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.
- Background: PubMed 15896428Ellegard 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Disease, run by Università Politecnica delle Marche.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of plasma phytosterol concentrations in preterm infants during parenteral nutrition and after only intravenous lipid stopping (time frame: 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 and 84 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02947594, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2018.