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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cholestasis, Prematurity, Gastroschisis, Intestinal Atresia, Necrotizing Enterocolitis

Intervention / Treatment
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* Dietary Supplement: Parenteral Nutrition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Maximum Age: 7 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cycling Parenteral Nutrition<br>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<br>* Parenteral Nutrition infused over 20 hours cycled with dextrose solution over 4 hours compared to Parenteral Nutrition infused continuously over 24 hours.<br>|
| Active Comparator: Continuous Parenteral Nutrition<br>Infants in this control group will receive infusion of carbohydrates/amino acids and intralipids continuously, over 24 hours. | Dietary Supplement: Parenteral Nutrition<br>* Parenteral Nutrition infused over 20 hours cycled with dextrose solution over 4 hours compared to Parenteral Nutrition infused continuously over 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PNALD, PNAC, Parenteral Nutrition-Associated Cholestasis, Congenital Anomalies of Gastrointestinal Tract