Prevention of Parenteral Nutrition-Associated Cholestasis With Cyclic Parenteral Nutrition in Infants

NCT01062815 | Terminated

• 1 other identifier: 20080651
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis to be Tested: Since the first description of intravenous alimentation over half a century ago, parenteral nutrition (PN) has become a common nutritional intervention for conditions characterized by inability to tolerate enteral feeds such as Short Bowel Syndrome, Chronic Intestinal Pseudoobstruction, Microvillus Inclusion Disease, Crohn's disease, multi-organ failure and prematurity. Parenteral Nutrition-Associated Liver Disease (PNALD) encompasses a spectrum of disease including cholestasis, hepatitis, steatosis and gallbladder sludge/stones which may progress to liver cirrhosis and even failure. There is a direct correlation between duration of parenteral nutrition and development of cholestasis in infants. There is evidence in animals and humans that cycling of parental nutrition, defined as infusing nutrients over a time period shorter than 24 hours, reduces cholestasis. There is also data that premature infants with gestational age (GA) \< 32 weeks and birth weight \<1500g, as well as infants with congenital anomalies of the gastrointestinal tract, are among those at highest risk of developing Parenteral Nutrition-Associated Cholestasis (PNAC). We therefore hypothesize that infants with gestational age (GA) \<32 weeks and birth weight (BW) between \<1500g, or with congenital anomaly of the gastrointestinal tract regardless of GA or BW, receiving PN over a period of 20 hours will have a decrease severity of PNAC, demonstrated by a lower peak direct bilirubin, compared to a similar control population receiving standard 24 hour infusion.

Conditions

Cholestasis; Prematurity; Gastroschisis; Intestinal Atresia; Necrotizing Enterocolitis

Keywords

PNALD; PNAC; Parenteral Nutrition-Associated Cholestasis; Congenital Anomalies of Gastrointestinal Tract

Outcome Measures

Primary Outcomes (1)

• The primary outcome is a decreased peak direct bilirubin in infants with GA <32 weeks and BW between <1500g, or with congenital anomaly of the gastrointestinal tract regardless of GA or BW, requiring prolonged PN (receiving >75% PN on dol 7).

  Peak direct bilirubin during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days)

Secondary Outcomes (3)

• A secondary outcome is to determine if the incidence of PN- Associated Cholestasis is lower in infants receiving cyclic PN over 20 hours compared to infants receiving standard continuous PN over 24 hours.

  Incidence of cholestasis (direct bilirubin >2mg/dL) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days)

• A secondary outcome in infants who develop PN-Associated Cholestasis is to evaluate if those receiving cyclic PN will have a shorter duration of cholestasis compared to infants receiving continuous PN.

  Duration of cholestasis (# of days direct bilirubin > 2mg/dL) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days) .

• A secondary outcome is to evaluate if infants receiving cyclic PN will have equivalent rates of growth compared to infants receiving continuous PN.

  Rate of growth (g of weight and cm of length and head circumference gained per week) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days).

Study Arms (2)

Cycling Parenteral Nutrition

EXPERIMENTAL

Infants in the intervention cycling group will receive infusion of carbohydrate/amino acids and intralipid over a 20-hour period. During the 4-hour window period, infants in this group will receive dextrose solution only at the same rate calculated for the carbohydrate/amino acid infusion.

Dietary Supplement: Parenteral Nutrition

Continuous Parenteral Nutrition

ACTIVE COMPARATOR

Infants in this control group will receive infusion of carbohydrates/amino acids and intralipids continuously, over 24 hours.

Dietary Supplement: Parenteral Nutrition

Interventions

Parenteral Nutrition DIETARY_SUPPLEMENT

Parenteral Nutrition infused over 20 hours cycled with dextrose solution over 4 hours compared to Parenteral Nutrition infused continuously over 24 hours.

Continuous Parenteral Nutrition; Cycling Parenteral Nutrition

Eligibility Criteria

• Age: Up to 7 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants expected to need prolonged PN (receiving \>75% PN on dol 7) with the following risk factors:
• Prematurity with gestational age (GA) \<32 weeks AND birth weight \<1500g. OR
• Congenital anomaly of the gastrointestinal tract regardless of GA or BW
• Screening direct bilirubin prior to the initiation of parenteral nutrition \<2mg/dL.

You may not qualify if:

• Infants with major congenital anomalies, other than those of the gastrointestinal tract.
• Infants with known obstruction of the hepatobiliary tract.
• Infants with suspected congenital infection or suspected genetic/metabolic syndrome predisposing them to cholestasis based on direct bilirubin \> 2mg/dL prior to instituting PN.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

Holtz's Children's Hospital- University of Miami/Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Related Publications (1)

• Amari S, Shahrook S, Namba F, Ota E, Mori R. Branched-chain amino acid supplementation for improving growth and development in term and preterm neonates. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD012273. doi: 10.1002/14651858.CD012273.pub2.

  PMID: 33006765 DERIVED

MeSH Terms

Conditions

Cholestasis; Premature Birth; Gastroschisis; Intestinal Atresia; Enterocolitis, Necrotizing

Interventions

Parenteral Nutrition

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hernia, Abdominal; Hernia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Digestive System Abnormalities; Intestinal Diseases; Gastrointestinal Diseases; Enterocolitis; Gastroenteritis

Intervention Hierarchy (Ancestors)

Feeding Methods; Therapeutics; Nutritional Support; Nutrition Therapy

Study Officials

• Lesley Smith, MD, MBA

  University of Miami, Dept of Pediatrics, Division of GI, Hepatology and Nutrition

  PRINCIPAL INVESTIGATOR

• Jennifer Garcia, MD

  University of Miami, Dept of Pediatrics, Division of GI, Hepatology and Nutrition

  STUDY DIRECTOR

• Teresa DelMoral, MD MPH

  University of Miami, Dept of Pediatrics, Division of Neonatology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 3, 2010
• First Posted: February 4, 2010
• Study Start: February 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: November 23, 2015

Record last verified: 2015-11

Locations

US (1)