CholestasisPhase 1NCT00512629
Cholestasis Prevention: Efficacy of IV Fish Oil
A Phase 1 study testing Omegaven and Intralipid in people with Cholestasis and Parenteral Nutrition, run by Boston Children's Hospital at 1 site in United States.
Trial summary
Parenteral nutrition (PN) solutions are life saving in patients with surgical gastrointestinal diseases. However, the use of PN in pediatric populations, especially premature infants, is frequently associated with liver injury that may ultimately result in hepatic failure. Read more about this study
- Who is it for?
- Ages Up to 3 months
- Conditions the study is for
- Cholestasis, Parenteral Nutrition
- What is being tested?
- Omegaven and Intralipid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Dec 2011
- Phase
- Phase 1
- 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 Up to 3 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Congenital or acquired gastrointestinal disease requiring surgical intervention [such as Midgut volvulus, Gastroschisis-(with known or suspected atresia(s), perforation(s) requiring a jejunostomy, or bowel resections > 20cm), Omphalocele, Jejunal atresia or NEC-(no peritoneal drains) or duodenal atresia] ; and
- Expected dependence on parenteral nutrition for full or partial nutritional support for an anticipated duration of therapy of at least 21 days; Subjects will be judged by their clinical team to require PN support a minimum of 21 days based on the following criteria: inability to tolerate enteral feedings, lack of audible bowel sounds, contraindications to initiation of enteral feedings (e.g., grossly bloody stools or other sign of intestinal ischemia, hypotension, bilious emesis, or clinical or radiographic evidence of bowel obstruction); and
- Neonates and infants < 3 months of age (postnatally); and
- Gestational age > 28 weeks; and
- Baseline direct bilirubin less than 1.0 mg/dL (normal); and
- Weight > 1 kg
Who cannot join
- Exposure to soybean oil fat emulsion for greater than three weeks (>21 days) at time of enrollment
- Known or suspected intolerance or allergy to any of the components of the study IFE, including fish, soy or egg protein
- Inability to obtain written informed consent prior to the baseline labs
- The patient is enrolled in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team)
- Intention to transfer care to another patient facility within 3 months of baseline labs
- Any serum triglyceride level greater than 400 mg/dL at baseline
Show all 16Show fewer
- History of severe hemolytic disorders or INR greater than 1.5 at baseline (INR cutoff of greater than 2 for babies less than 1 week of age)
- History of shock requiring vasopressors (dopamine equal or less than 20 micrograms/kilogram/minute is allowed; all other use of vasopressors is excluded)
- Preexisting liver disease, regardless of etiology
- Hemodynamically unstable as judged by PI
- Renal failure (creatinine greater than 0.4 mg/dL unless less than 1 month of age-then at the PI's discretion)
- Patient previously had STEP (Serial Transverse Enteroplasty Procedure)
- Patient is currently on ECMO or nitric oxide
- GGTP > 80 mg/L at baseline
- Weight < 1 kg at time of enrollment
- Gestational age < 28 weeks at time of enrollment
Trial locations and contacts
1 site in 1 country.
United States1 site
Childrens's Hospital Boston
Boston, Massachusetts, 02115
About this study
Parenteral nutrition (PN) solutions are life saving in patients with surgical gastrointestinal diseases. However, the use of PN in pediatric populations, especially premature infants, is frequently associated with liver injury that may ultimately result in hepatic failure. In studies conducted in a murine model, we observed that intravenous fat emulsions (IFE) comprised of omega-3 fatty acids were able to prevent the development of cholestasis, a common precursor of PN-associated liver disease, as well as reverse preexisting PNALD through a combination of factors, including improved triglyceride clearance coupled with anti-inflammatory properties. In a case series treating patients with hepatic cholestasis, serum bilirubin levels decreased markedly after the parenteral administration of an omega-3 fatty acid based fat emulsion (Omegaven®). Patients tolerated this therapy and no adverse reactions attributed to its use were observed. Based on results of these previous studies, we propose to conduct a randomized trial aiming to gain preliminary evidence of efficacy of an omega-3 fatty acid based IFE in preventing PNALD in children with intestinal failure
Read the detailed description
We propose to conduct a randomized controlled clinical trial to determine whether the use of an omega-3 fatty acid based IFE in infants with surgical gastrointestinal disease will improve clinical outcomes compared to infants treated with standard IFE up to 6 months post randomization. Neonates and infants < 3 months old (postnatally) with surgical gastrointestinal disease (defined as congenital or acquired gastrointestinal disease requiring PN for more than 21 days) will be eligible for enrollment. Patients who meet all inclusion and exclusion criteria will be randomized to receive PN with either Intralipid® or Omegaven®. The appearance of both IFEs is indistinguishable, so patients, families and the medical care team will be blinded to treatment group allocation. Aside from the IFE type, the clinical care of both groups of infants will remain unchanged, including standard use of feeding advancement protocols, and treatment of underlying gastrointestinal and other diseases.
- Conditions
- Cholestasis, Parenteral Nutrition
- Being tested
- Omegaven, Intralipid
- Keywords
- PN, cholestasis, gastrointestinal disease in infants, short bowel syndrome
- Medical subject headings
- Cholestasis, Hyperphagia, Short Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OmegavenDrug
Omegaven is a fish based intravenous fat emulsion
IntralipidDrug
Intralipid is a plant based intravenous fat emulsion
| Study group | Role | What they receive |
|---|---|---|
| Omegaven | Experimental | Omegaven is a fish based intravenous fat emulsion Receives: Drug: Omegaven |
| Intralipid | Active comparator | Not described Receives: Drug: Intralipid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence vs. absence of PN-associated cholestasis (PNAC)
The definition of "Presence vs. Absence of PNAC" will vary with the post conceptual age of the child. In infants > 40 weeks post conceptual age, we will define PN-associated cholestasis as four consecutive measurements (> 6 days apart) of serum direct bilirubin > 2.0mg/dL obtained over a 30 day period in the absence of other demonstrable etiologies of cholestasis. Due to hepatic immaturity, for infants < 40 weeks post conceptual age, PN associated cholestasis will be defined as four consecutive measurements (> 6 days apart) of serum direct bilirubin > 2.0mg/dL obtained over a 42 day period.
Measured: 6 months
Secondary outcomes (9)
Fatty acid profiles
(i.e., Mead acid levels, triene:tetraene ratios, total omega-3 and omega-6 fatty acid levels, arachidonic acid levels)
Measured: 6 months
Weight and height gain
Measured: 6 months
Liver function tests
(i.e. serum triglycerides, cholesterol, ALT, AST and total and direct bilirubin levels)
Measured: 6 months
Death from PNALD liver or liver/gastrointestinal tract transplant.
Measured: 1 year
Duration of parenteral nutrition
(i.e. enteral feeding tolerance, including days to reach full enteral feeding (approximately 100-125kcal/kg/d + 10%) after randomization and the number of episodes of feeding intolerance (defined as an interruption of enteral feedings for > 12 hrs) , number of infants requiring TPN providing > 10% of total daily fluid volume at 12 weeks after randomization, and duration of TPN providing > 10% of total daily fluid intake)
Measured: 6 months
Frequency of blood stream infections
Measured: 6 months
Inflammatory markers (C-reactive protein), cytokine levels
Measured: 6 months
Incidence and severity of ROP
Measured: 6 months
Neurodevelopment Assessments
Neurodevelopment will be assessed at 6, 12, and 24 months (corrected) using Bayley Scales of Infant Development III(mean total, cognitive, language, and motor scaled score; and frequency of each score <70). The MSD parent questionnaire will be mailed at 12 and 24 months (corrected); and the Parent Report of Children's Abilities - Revised (PARCA-R) parent questionnaire will be mailed at 24 months (coorected).
Measured: 6, 12, & 24 months (corrected for gestational age)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2007 (estimated)
- Study startJul 2007
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CholestasisStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mark Puder, Boston Children's Hospital
- Investigators
- Mark Puder, MD, PhD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00512629
- Sponsor's protocol ID
- 06-03-0105
- Other IDs
- 1R01FD003436-01
- Status last verified
- Dec 2020
- First submitted
- 6 Aug 2007
- Last updated
- 3 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nehra D, Fallon EM, Potemkin AK, Voss SD, Mitchell PD, Valim C, Belfort MB, Bellinger DC, Duggan C, Gura KM, Puder M. A comparison of 2 intravenous lipid emulsions: interim analysis of a randomized controlled trial. JPEN J Parenter Enteral Nutr. 2014 Aug;38(6):693-701. doi: 10.1177/0148607113492549. Epub 2013 Jun 14.
PubMed 23770843
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholestasis Prevention: Efficacy of IV Fish Oil
- ClinicalTrials.gov ID
- NCT00512629
- Acronym / sponsor ID
- 06-03-0105
- Conditions
- Cholestasis, Parenteral Nutrition
- Keywords
- PN, cholestasis, gastrointestinal disease in infants, short bowel syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- Jul 2007
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 8 Aug 2007 (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 (PN) solutions are life saving in patients with surgical gastrointestinal diseases. However, the use of PN in pediatric populations, especially premature infants, is frequently associated with liver injury that may ultimately result in hepatic failure. In studies conducted in a murine model, we observed that intravenous fat emulsions (IFE) comprised of omega-3 fatty acids were able to prevent the development of cholestasis, a common precursor of PN-associated liver disease, as well as reverse preexisting PNALD through a combination of factors, including improved triglyceride clearance coupled with anti-inflammatory properties. In a case series treating patients with hepatic cholestasis, serum bilirubin levels decreased markedly after the parenteral administration of an omega-3 fatty acid based fat emulsion (Omegaven®). Patients tolerated this therapy and no adverse reactions attributed to its use were observed. Based on results of these previous studies, we propose to conduct a randomized trial aiming to gain preliminary evidence of efficacy of an omega-3 fatty acid based IFE in preventing PNALD in children with intestinal failure
Detailed description
We propose to conduct a randomized controlled clinical trial to determine whether the use of an omega-3 fatty acid based IFE in infants with surgical gastrointestinal disease will improve clinical outcomes compared to infants treated with standard IFE up to 6 months post randomization. Neonates and infants < 3 months old (postnatally) with surgical gastrointestinal disease (defined as congenital or acquired gastrointestinal disease requiring PN for more than 21 days) will be eligible for enrollment. Patients who meet all inclusion and exclusion criteria will be randomized to receive PN with either Intralipid® or Omegaven®. The appearance of both IFEs is indistinguishable, so patients, families and the medical care team will be blinded to treatment group allocation. Aside from the IFE type, the clinical care of both groups of infants will remain unchanged, including standard use of feeding advancement protocols, and treatment of underlying gastrointestinal and other diseases.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Omegaven | Experimental | Drug: OmegavenOmegaven is a fish based intravenous fat emulsion |
| Intralipid | Active comparator | Drug: Intralipid |
Who may qualify
- Ages
- Up to 3 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Congenital or acquired gastrointestinal disease requiring surgical intervention [such as Midgut volvulus, Gastroschisis-(with known or suspected atresia(s), perforation(s) requiring a jejunostomy, or bowel resections > 20cm), Omphalocele, Jejunal atresia or NEC-(no peritoneal drains) or duodenal atresia] ; and
- Expected dependence on parenteral nutrition for full or partial nutritional support for an anticipated duration of therapy of at least 21 days; Subjects will be judged by their clinical team to require PN support a minimum of 21 days based on the following criteria: inability to tolerate enteral feedings, lack of audible bowel sounds, contraindications to initiation of enteral feedings (e.g., grossly bloody stools or other sign of intestinal ischemia, hypotension, bilious emesis, or clinical or radiographic evidence of bowel obstruction); and
- Neonates and infants < 3 months of age (postnatally); and
- Gestational age > 28 weeks; and
- Baseline direct bilirubin less than 1.0 mg/dL (normal); and
Key exclusion criteria (16 listed)
- Exposure to soybean oil fat emulsion for greater than three weeks (>21 days) at time of enrollment
- Known or suspected intolerance or allergy to any of the components of the study IFE, including fish, soy or egg protein
- Inability to obtain written informed consent prior to the baseline labs
- The patient is enrolled in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team)
- Intention to transfer care to another patient facility within 3 months of baseline labs
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 |
|---|---|---|
| OmegavenOmegaven is a fish based intravenous fat emulsion | Drug | Omegaven |
| IntralipidIntralipid is a plant based intravenous fat emulsion | Drug | Intralipid |
Primary outcome
Presence vs. absence of PN-associated cholestasis (PNAC)
Time frame: 6 months
The definition of "Presence vs. Absence of PNAC" will vary with the post conceptual age of the child. In infants > 40 weeks post conceptual age, we will define PN-associated cholestasis as four consecutive measurements (> 6 days apart) of serum direct bilirubin > 2.0mg/dL obtained over a 30 day period in the absence of other demonstrable etiologies of cholestasis. Due to hepatic immaturity, for infants < 40 weeks post conceptual age, PN associated cholestasis will be defined as four consecutive measurements (> 6 days apart) of serum direct bilirubin > 2.0mg/dL obtained over a 42 day period.
9 secondary outcomes
Fatty acid profiles
Time frame: 6 months
Weight and height gain
Time frame: 6 months
Liver function tests
Time frame: 6 months
Death from PNALD liver or liver/gastrointestinal tract transplant.
Time frame: 1 year
Duration of parenteral nutrition
Time frame: 6 months
Frequency of blood stream infections
Time frame: 6 months
Inflammatory markers (C-reactive protein), cytokine levels
Time frame: 6 months
Incidence and severity of ROP
Time frame: 6 months
Neurodevelopment Assessments
Time frame: 6, 12, & 24 months (corrected for gestational age)
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 3 Dec 2020.
- Results publication: PubMed 23770843Nehra D, Fallon EM, Potemkin AK, Voss SD, Mitchell PD, Valim C, Belfort MB, Bellinger DC, Duggan C, Gura KM, Puder M. A comparison of 2 intravenous lipid emulsions: interim analysis of a randomized controlled trial. JPEN J Parenter Enteral Nutr. 2014 Aug;38(6):693-701. doi: 10.1177/0148607113492549. Epub 2013 Jun 14.
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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.
Mark Puder, MD, PhD principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Omegaven and Intralipid in people with Cholestasis and Parenteral Nutrition, run by Boston Children's Hospital at 1 site 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 6 inclusion and 16 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 3 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Presence vs. absence of PN-associated cholestasis (PNAC) (time frame: 6 months). 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 NCT00512629, which also lists 1 linked publication.
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 3 Dec 2020.