Clinical trial NCT01062815: Prevention of Parenteral Nutrition-Associated Cholestasis With Cyclic Parenteral Nutrition in Infants
Official title: Prevention of Parenteral Nutrition-Associated Cholestasis With Cyclic Parenteral Nutrition in Infants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Cholestasis
Prematurity
Gastroschisis
Intestinal Atresia
Necrotizing Enterocolitis
Keywords: PNALD
PNAC
Parenteral Nutrition-Associated Cholestasis
Congenital Anomalies of Gastrointestinal Tract
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2010-02-04
Enrollment: 48
Sex: ALL
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

1. Infants expected to need prolonged PN (receiving \>75% PN on dol 7) with the following risk factors:

   1. Prematurity with gestational age (GA) \<32 weeks AND birth weight \<1500g. OR
   2. Congenital anomaly of the gastrointestinal tract regardless of GA or BW
2. Screening direct bilirubin prior to the initiation of parenteral nutrition \<2mg/dL.

Exclusion Criteria:

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

Primary outcomes:
measure: 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).
timeFrame: Peak direct bilirubin during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days)
Secondary outcomes:
measure: 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.
timeFrame: Incidence of cholestasis (direct bilirubin >2mg/dL) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days)
measure: 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.
timeFrame: Duration of cholestasis (# of days direct bilirubin > 2mg/dL) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days) .
measure: A secondary outcome is to evaluate if infants receiving cyclic PN will have equivalent rates of growth compared to infants receiving continuous PN.
timeFrame: 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).
Other outcomes:
Locations:
city: Miami
country: United States
facility: Holtz's Children's Hospital- University of Miami/Jackson Memorial Hospital
state: Florida
Study officials:
affiliation: University of Miami, Dept of Pediatrics, Division of GI, Hepatology and Nutrition
name: Lesley Smith, MD, MBA
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami, Dept of Pediatrics, Division of GI, Hepatology and Nutrition
name: Jennifer Garcia, MD
role: STUDY_DIRECTOR
affiliation: University of Miami, Dept of Pediatrics, Division of Neonatology
name: Teresa DelMoral, MD MPH
role: STUDY_CHAIR
References:
citation: 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.