Cholestasis Prevention: Efficacy of IV Fish Oil

Tracking Information
First Submitted Date ICMJE	August 6, 2007
First Posted Date ICMJE	August 8, 2007
Last Update Posted Date	December 15, 2011
Study Start Date ICMJE	July 2007
Actual Primary Completion Date	December 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 25, 2010)	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.
Original Primary Outcome Measures ICMJE; (submitted: August 7, 2007)	The primary study outcome will be the presence (vs. absence) of PN -associated cholestasis among infants with surgical gastrointestinal disease. [ Time Frame: 3 months from start of treatment ]
Change History	Complete list of historical versions of study NCT00512629 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 25, 2010)	Fatty acid profiles [ Time Frame: 6 months ](i.e., Mead acid levels, triene:tetraene ratios, total omega-3 and omega-6 fatty acid levels, arachidonic acid levels); Weight and height gain [ Time Frame: 6 months ]; Liver function tests [ Time Frame: 6 months ](i.e. serum triglycerides, cholesterol, ALT, AST and total and direct bilirubin levels); Death from PNALD liver or liver/gastrointestinal tract transplant. [ Time Frame: 1 year ]; Duration of parenteral nutrition [ Time Frame: 6 months ](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); 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) ]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).
Original Secondary Outcome Measures ICMJE; (submitted: August 7, 2007)	Secondary outcomes will include: fatty acid profiles, arachidonic essential fatty acid levels, triglycerides, cholesterol, ALT, AST, weight and height gain death [ Time Frame: 3 months and at 6 months from start of treatment ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Cholestasis Prevention: Efficacy of IV Fish Oil
Official Title ICMJE	Cholestasis Prevention: Efficacy of IV Fish Oil
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition ICMJE	Cholestasis; Parenteral Nutrition
Intervention ICMJE	Drug: Omegaven Omegaven is a fish based intravenous fat emulsion; Drug: Intralipid Intralipid is a plant based intravenous fat emulsion
Study Arms	Experimental: Omegaven Omegaven is a fish based intravenous fat emulsion Intervention: Drug: Omegaven; Active Comparator: Intralipid Intervention: Drug: Intralipid
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 14, 2011)	19
Original Estimated Enrollment ICMJE; (submitted: August 7, 2007)	30
Actual Study Completion Date	December 2011
Actual Primary Completion Date	December 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion criteria (all of the following): 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 Exclusion criteria(any one of the following): 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; 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
Sex/Gender	Sexes Eligible for Study: All
Ages	up to 3 Months (Child)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00512629
Other Study ID Numbers ICMJE	06-03-0105; 1R01FD003436-01 ( U.S. FDA Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Boston Children’s Hospital
Study Sponsor ICMJE	Boston Children’s Hospital
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Mark Puder, MD, PhD Boston Children’s Hospital
PRS Account	Boston Children’s Hospital
Verification Date	December 2011
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP