Prevention of Parenteral Nutrition-Associated Cholestasis With Cyclic Parenteral Nutrition in Infants
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Cholestasis Prematurity Gastroschisis Intestinal Atresia Necrotizing Enterocolitis |
Drug: Parenteral Nutrition |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Prevention |
| Official Title: | Prevention of Parenteral Nutrition-Associated Cholestasis With Cyclic Parenteral Nutrition in Infants |
- 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). [ Time Frame: Peak direct bilirubin during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days) ] [ Designated as safety issue: No ]
- 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. [ Time Frame: Incidence of cholestasis (direct bilirubin >2mg/dL) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days) ] [ Designated as safety issue: No ]
- 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. [ Time Frame: Duration of cholestasis (# of days direct bilirubin > 2mg/dL) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days) . ] [ Designated as safety issue: No ]
- A secondary outcome is to evaluate if infants receiving cyclic PN will have equivalent rates of growth compared to infants receiving continuous PN. [ Time Frame: 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). ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 120 |
| Study Start Date: | February 2009 |
| Estimated Primary Completion Date: | June 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Cycling Parenteral Nutrition
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.
|
Drug: Parenteral Nutrition
Parenteral Nutrition infused over 20 hours cycled with dextrose solution over 4 hours compared to Parenteral Nutrition infused continuously over 24 hours.
|
|
No Intervention: Continuous Parenteral Nutrition
Infants in this control group will receive infusion of carbohydrates/amino acids and intralipids continuously, over 24 hours.
|
Drug: Parenteral Nutrition
Parenteral Nutrition infused over 20 hours cycled with dextrose solution over 4 hours compared to Parenteral Nutrition infused continuously over 24 hours.
|
Eligibility| Ages Eligible for Study: | up to 7 Days |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Contact: Jennifer Garcia, MD | 305-243-3166 | JGarcia2@med.miami.edu |
| Contact: Teresa DelMoral, MD | 305-243-4531 | TDelMoral@med.miami.edu |
| United States, Florida | |
| Holtz's Children's Hospital- University of Miami/Jackson Memorial Hospital | Recruiting |
| Miami, Florida, United States, 33136 | |
| Contact: Jennifer Garcia, MD 305-243-3166 JGarcia2@med.miami.edu | |
| Contact: Teresa DelMoral, MD MPH 305-243-4531 TDelMoral@med.miami.ed | |
| Sub-Investigator: Jennifer Garcia, MD | |
| Sub-Investigator: Teresa DelMoral, MD, MPH | |
| Principal Investigator: Lesley Smith, MD, MBA | |
| Principal Investigator: | Lesley Smith, MD, MBA | University of Miami, Dept of Pediatrics, Division of GI, Hepatology and Nutrition |
| Study Director: | Jennifer Garcia, MD | University of Miami, Dept of Pediatrics, Division of GI, Hepatology and Nutrition |
| Study Chair: | Teresa DelMoral, MD MPH | University of Miami, Dept of Pediatrics, Division of Neonatology |
More Information
No publications provided
| Responsible Party: | Lesley Smith MD MBA, University of Miami, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition |
| ClinicalTrials.gov Identifier: | NCT01062815 History of Changes |
| Other Study ID Numbers: | 20080651 |
| Study First Received: | February 3, 2010 |
| Last Updated: | February 3, 2010 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of Miami:
|
PNALD PNAC Parenteral Nutrition-Associated Cholestasis Congenital Anomalies of Gastrointestinal Tract |
Additional relevant MeSH terms:
|
Cholestasis Enterocolitis Intestinal Atresia Gastroschisis Enterocolitis, Necrotizing Bile Duct Diseases Biliary Tract Diseases Digestive System Diseases Gastroenteritis |
Gastrointestinal Diseases Intestinal Diseases Digestive System Abnormalities Congenital Abnormalities Musculoskeletal Abnormalities Musculoskeletal Diseases Hernia, Abdominal Hernia Pathological Conditions, Anatomical |
ClinicalTrials.gov processed this record on May 23, 2013