CholestasisPhase 4NCT01373918
Low Dose Fat for the Prevention of Liver Disease in Babies With Gastrointestinal Disorders
A Phase 4 study testing Intralipid in people with Cholestasis, run by University of California, Los Angeles at 2 sites in United States.
Trial summary
Neonates with congenital/acquired gastrointestinal disorders are at high risk for Parenteral Nutrition Associated Cholestasis (PNAC). Besides enteral nutrition, standard therapies to prevent and treat PNAC have been limited and marginal. Read more about this study
- Who is it for?
- Ages 1 minute to 5 days
- Conditions the study is for
- Cholestasis
- What is being tested?
- Intralipid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2010to Jul 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 minute to 5 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- congenital or acquired gastrointestinal disorder
- age less than 5 days of life
Who cannot join
- congenital intrauterine infection know to be associated with liver involvement
- known structural liver abnormalities
- known genetic disorders (trisomy 21, 13, and 18)
- inborn errors of metabolism
- infants meeting the criteria for terminal illness (ph:6.8>2 hours)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of California, Los Angeles
Los Angeles, California, 90095
Saint Louis University
St Louis, Missouri, 63104
About this study
Official title: Low Dose Parenteral Fat for the Prevention of Parenteral Nutrition Associated Cholestasis in Neonates With Congenital/Acquired Gastrointestinal Disorders
Neonates with congenital/acquired gastrointestinal disorders are at high risk for Parenteral Nutrition Associated Cholestasis (PNAC). Besides enteral nutrition, standard therapies to prevent and treat PNAC have been limited and marginal. Recently, the dose and composition of standard intravenous fat emulsions have implicated in the development and progression of PNAC.
In this study, neonates with congenital/acquired gastrointestinal disorders will be randomized, in a unblinded fashion, to receive either the standard dose of an intravenous omega-6 fatty acid emulsion or a low dose of an intravenous omega-6 fatty acid emulsion throughout their course of PN or until hospital discharge, death or 100 days of life, whichever comes first. The primary outcome will be the presence of cholestasis.
Read the detailed description
Parenteral Nutrition (PN) acts as an intravenous source of both macronutrients and micronutrients when enteral feeds are not possible. Intravenous fat emulsions often supplement PN and provide a dense source of non-protein calories and essential fatty acids. Although PN is life-sustaining, it is associated with a myriad of life-threatening complications including Parenteral Nutrition Associated Cholestasis (PNAC). Children dependent on PN for an extended period of time are high risk for liver failure.
The etiology of PNAC remains poorly understood. Neonates with congenital and acquired gastrointestinal disorders are at high risk for PNAC and its subsequent complications. Examples of these gastrointestinal disorders include gastroschisis, volvulus, atresias, dysmotility and malabsorption disorders, pseudo-obstruction, and Hirschsprung's disease. These disorders often render the gut non-functional for extended periods of time. As a result, these patients become PN-dependent and develop PNAC.
Specific PN components have been implicated in the pathogenesis of PNAC. More recently, standard intravenous fat emulsions have been labeled as one of the main culprits contributing to PNAC. Standard intravenous fat emulsions are dosed as high as 4 g/kg/d and are derived from soybean and/or safflower oil, which are rich in omega-6 fatty acids and phytosterols and contain a paucity of omega-3 fatty acids. It is unclear if the dose or high omega-6 fatty acid:omega-3 fatty acid ratio and phytosterols is responsible for the development of PNAC.
The primary specific aim of this study is to determine if PNAC is related to the amount of standard intravenous fat emulsion administered to neonates with congenital/acquired gastrointestinal disorders. The investigators hypothesize that the PNAC is unrelated to the dose of intravenous fat emulsions. To test this hypothesis, neonates with congenital/acquired gastrointestinal disorders will be randomized to low dose standard soybean based parenteral fat, 1 g/kg/d, or standard dose soybean parenteral fat, 3 g/kg/d. Secondary outcomes include: mortality rate, length of stay, and anthropometric measurements at 28 days of life and at the end of the hospital stay, which is expected to be an average of 5 weeks.
- Conditions
- Cholestasis
- Being tested
- Intralipid
- Keywords
- cholestasis, neonates, parenteral nutrition, gastrointestinal disorders
- Medical subject headings
- Cholestasis, Hyperphagia, Gastrointestinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IntralipidDrug
Also called soybean oil
The subject will receive 1 g/kg/d of the standard intravenous fat emulsion while receiving Parenteral Nutrition until discharge from the hospital, death or 100 days of life, whichever comes first.
IntralipidDrug
Also called soybean oil
The subject will receive 3 g/kg/d of the standard intravenous fat emulsion while receiving Parenteral Nutrition until discharge from the hospital, death or 100 days of life, whichever comes first.
| Study group | Role | What they receive |
|---|---|---|
| low dose intravenous fat emulsion | Experimental | Subjects in this arm will receive approximately 1 g/kg/d IV of intravenous soybean oil (Intralipid). Receives: Drug: Intralipid |
| standard dose intravenous fat emulsion | Active comparator | Subjects in this arm will receive approximately 3 g/kg/d IV of intravenous soybean oil (Intralipid). Receives: Drug: Intralipid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence of Cholestasis
Cholestasis will be defined by a direct bilirubin > 2 mg/dL
Measured: prior to 100 days of life, hospital discharge, or death whichever comes first
Secondary outcomes (3)
Mortality Rate
death
Measured: at the end of the hospital stay which is expected to be an average of 5 weeks
Anthropometric Measurements
Growth will be assessed by growth velocity at 28 days of age
Measured: 28 days of age
Anthropometric Measurements
Growth will be assessed by weight at the time of hospital discharge (approximately 5 weeks)
Measured: approximately 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2011 (estimated)
- Study startDec 2010
- Primary completionJul 2014
- Study completionJul 2014
Why it stopped: The study was terminated due to slow enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CholestasisStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- St. Louis University
- Responsible party
- Principal investigator, Kara L. Calkins, MD, University of California, Los Angeles
- Investigators
- Kara L Calkins, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01373918
- Sponsor's protocol ID
- 10-001714
- Status last verified
- May 2016
- First submitted
- 6 Jun 2011
- Last updated
- 16 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Dose Parenteral Fat for the Prevention of Parenteral Nutrition Associated Cholestasis in Neonates With Congenital/Acquired Gastrointestinal Disorders
- ClinicalTrials.gov ID
- NCT01373918
- Acronym / sponsor ID
- 10-001714
- Conditions
- Cholestasis
- Keywords
- cholestasis, neonates, parenteral nutrition, gastrointestinal disorders
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to slow enrollment.
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- St. Louis University
- Study start
- Dec 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 15 Jun 2011 (estimated)
- Results
- Posted 16 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neonates with congenital/acquired gastrointestinal disorders are at high risk for Parenteral Nutrition Associated Cholestasis (PNAC). Besides enteral nutrition, standard therapies to prevent and treat PNAC have been limited and marginal. Recently, the dose and composition of standard intravenous fat emulsions have implicated in the development and progression of PNAC.
In this study, neonates with congenital/acquired gastrointestinal disorders will be randomized, in a unblinded fashion, to receive either the standard dose of an intravenous omega-6 fatty acid emulsion or a low dose of an intravenous omega-6 fatty acid emulsion throughout their course of PN or until hospital discharge, death or 100 days of life, whichever comes first. The primary outcome will be the presence of cholestasis.
Detailed description
Parenteral Nutrition (PN) acts as an intravenous source of both macronutrients and micronutrients when enteral feeds are not possible. Intravenous fat emulsions often supplement PN and provide a dense source of non-protein calories and essential fatty acids. Although PN is life-sustaining, it is associated with a myriad of life-threatening complications including Parenteral Nutrition Associated Cholestasis (PNAC). Children dependent on PN for an extended period of time are high risk for liver failure.
The etiology of PNAC remains poorly understood. Neonates with congenital and acquired gastrointestinal disorders are at high risk for PNAC and its subsequent complications. Examples of these gastrointestinal disorders include gastroschisis, volvulus, atresias, dysmotility and malabsorption disorders, pseudo-obstruction, and Hirschsprung's disease. These disorders often render the gut non-functional for extended periods of time. As a result, these patients become PN-dependent and develop PNAC.
Specific PN components have been implicated in the pathogenesis of PNAC. More recently, standard intravenous fat emulsions have been labeled as one of the main culprits contributing to PNAC. Standard intravenous fat emulsions are dosed as high as 4 g/kg/d and are derived from soybean and/or safflower oil, which are rich in omega-6 fatty acids and phytosterols and contain a paucity of omega-3 fatty acids. It is unclear if the dose or high omega-6 fatty acid:omega-3 fatty acid ratio and phytosterols is responsible for the development of PNAC.
The primary specific aim of this study is to determine if PNAC is related to the amount of standard intravenous fat emulsion administered to neonates with congenital/acquired gastrointestinal disorders. The investigators hypothesize that the PNAC is unrelated to the dose of intravenous fat emulsions. To test this hypothesis, neonates with congenital/acquired gastrointestinal disorders will be randomized to low dose standard soybean based parenteral fat, 1 g/kg/d, or standard dose soybean parenteral fat, 3 g/kg/d. Secondary outcomes include: mortality rate, length of stay, and anthropometric measurements at 28 days of life and at the end of the hospital stay, which is expected to be an average of 5 weeks.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| low dose intravenous fat emulsion | Experimental | Drug: IntralipidSubjects in this arm will receive approximately 1 g/kg/d IV of intravenous soybean oil (Intralipid). |
| standard dose intravenous fat emulsion | Active comparator | Drug: IntralipidSubjects in this arm will receive approximately 3 g/kg/d IV of intravenous soybean oil (Intralipid). |
Who may qualify
- Ages
- 1 minute to 5 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- congenital or acquired gastrointestinal disorder
- age less than 5 days of life
Key exclusion criteria (5 listed)
- congenital intrauterine infection know to be associated with liver involvement
- known structural liver abnormalities
- known genetic disorders (trisomy 21, 13, and 18)
- inborn errors of metabolism
- infants meeting the criteria for terminal illness (ph:6.8>2 hours)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IntralipidAlso: soybean oilThe subject will receive 1 g/kg/d of the standard intravenous fat emulsion while receiving Parenteral Nutrition until discharge from the hospital, death or 100 days of life, whichever comes first. | Drug | low dose intravenous fat emulsion |
| IntralipidAlso: soybean oilThe subject will receive 3 g/kg/d of the standard intravenous fat emulsion while receiving Parenteral Nutrition until discharge from the hospital, death or 100 days of life, whichever comes first. | Drug | standard dose intravenous fat emulsion |
Primary outcome
Presence of Cholestasis
Time frame: prior to 100 days of life, hospital discharge, or death whichever comes first
Cholestasis will be defined by a direct bilirubin > 2 mg/dL
3 secondary outcomes
Mortality Rate
Time frame: at the end of the hospital stay which is expected to be an average of 5 weeks
Anthropometric Measurements
Time frame: 28 days of age
Anthropometric Measurements
Time frame: approximately 5 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Kara L Calkins, MD principal investigator
University of California, Los Angeles
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intralipid in people with Cholestasis, run by University of California, Los Angeles at 2 sites in United States.
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 2 inclusion and 5 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: stopped early, as of the sponsor's last update on 16 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Presence of Cholestasis (time frame: prior to 100 days of life, hospital discharge, or death whichever comes first). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jun 2016.