Cholestasis Prevention: Efficacy of IV Fish Oil

NCT00512629 | Completed Phase 1 DMC

• 2 other identifiers: 06-03-01051R01FD003436-01
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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

Conditions

Cholestasis; Parenteral Nutrition

Keywords

PN; cholestasis; gastrointestinal disease in infants; short bowel syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (9)

• Fatty acid profiles

  6 months

• Weight and height gain

  6 months

• Liver function tests

  6 months

• Death from PNALD liver or liver/gastrointestinal tract transplant.

  1 year

• Duration of parenteral nutrition

  6 months

Study Arms (2)

Omegaven

EXPERIMENTAL

Omegaven is a fish based intravenous fat emulsion

Drug: Omegaven

Intralipid

ACTIVE COMPARATOR

Drug: Intralipid

Interventions

Omegaven DRUG

Omegaven is a fish based intravenous fat emulsion

Omegaven

Intralipid DRUG

Intralipid is a plant based intravenous fat emulsion

Intralipid

Eligibility Criteria

• Age: Up to 3 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Childrens's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 23770843 RESULT

MeSH Terms

Conditions

Cholestasis; Hyperphagia; Short Bowel Syndrome

Interventions

fish oil triglycerides; soybean oil, phospholipid emulsion

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Postoperative Complications; Pathologic Processes

Study Officials

• Mark Puder, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Staff

Study Record Dates

• First Submitted: August 6, 2007
• First Posted: August 8, 2007
• Study Start: July 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 3, 2020

Record last verified: 2020-12

Locations

US (1)