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

University of Miami

Status: Terminated

Conditions: Prematurity; Necrotizing Enterocolitis; Gastroschisis; Cholestasis; Intestinal Atresia

Treatments: Dietary Supplement: Parenteral Nutrition

Study type: Interventional

Funder types: Other

Identifiers

NCT01062815

20080651

Details and patient eligibility

About

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.

Enrollment: 48 patients

Sex: All

Ages: Under 7 days old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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48 participants in 2 patient groups

Cycling Parenteral Nutrition

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Parenteral Nutrition

Continuous Parenteral Nutrition

Active Comparator group

Description:

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

Treatment:

Dietary Supplement: Parenteral Nutrition