Clinical trial NCT00512629: Cholestasis Prevention: Efficacy of IV Fish Oil
Official title: Cholestasis Prevention: Efficacy of IV Fish Oil
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cholestasis
Parenteral Nutrition
Keywords: PN
cholestasis
gastrointestinal disease in infants
short bowel syndrome
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2007-08-08
Enrollment: 19
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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. 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.

Eligibility criteria: Inclusion criteria (all of the following):

1. 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
2. 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
3. Neonates and infants \< 3 months of age (postnatally); and
4. Gestational age \> 28 weeks; and
5. Baseline direct bilirubin less than 1.0 mg/dL (normal); and
6. Weight \> 1 kg

Exclusion criteria(any one of the following):

1. Exposure to soybean oil fat emulsion for greater than three weeks (\>21 days) at time of enrollment
2. Known or suspected intolerance or allergy to any of the components of the study IFE, including fish, soy or egg protein
3. Inability to obtain written informed consent prior to the baseline labs
4. The patient is enrolled in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team)
5. Intention to transfer care to another patient facility within 3 months of baseline labs
6. Any serum triglyceride level greater than 400 mg/dL at baseline
7. 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)
8. History of shock requiring vasopressors (dopamine equal or less than 20 micrograms/kilogram/minute is allowed; all other use of vasopressors is excluded)
9. Preexisting liver disease, regardless of etiology
10. Hemodynamically unstable as judged by PI
11. Renal failure (creatinine greater than 0.4 mg/dL unless less than 1 month of age-then at the PI's discretion)
12. Patient previously had STEP (Serial Transverse Enteroplasty Procedure)
13. Patient is currently on ECMO or nitric oxide
14. GGTP \> 80 mg/L at baseline
15. Weight \< 1 kg at time of enrollment
16. Gestational age \< 28 weeks at time of enrollment

Primary outcomes:
measure: Presence vs. absence of PN-associated cholestasis (PNAC)
timeFrame: 6 months
Secondary outcomes:
measure: Fatty acid profiles
timeFrame: 6 months
measure: Weight and height gain
timeFrame: 6 months
measure: Liver function tests
timeFrame: 6 months
measure: Death from PNALD liver or liver/gastrointestinal tract transplant.
timeFrame: 1 year
measure: Duration of parenteral nutrition
timeFrame: 6 months
measure: Frequency of blood stream infections
timeFrame: 6 months
measure: Inflammatory markers (C-reactive protein), cytokine levels
timeFrame: 6 months
measure: Incidence and severity of ROP
timeFrame: 6 months
measure: Neurodevelopment Assessments
timeFrame: 6, 12, & 24 months (corrected for gestational age)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Childrens's Hospital Boston
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Mark Puder, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.