Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates

NCT00846963 | Completed Phase 2

• 1 other identifier: RC:127
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether ursodiol is effective in the treatment of parenteral nutrition associated cholestasis in neonates.

Conditions

Cholestasis

Keywords

parenteral nutrition associated cholestasis in neonates; parenteral nutrition induced cholestasis in preterms; Bile duct obstruction; biliary stasis

Outcome Measures

Primary Outcomes (1)

• Length of parenteral nutrition associated cholestasis (in days)

  at the end of cholestasis (when conjugated bilirubin < 34 mmol/L) average of 4 weeks.

Secondary Outcomes (5)

• Peak value of biomarkers associated with cholestasis (Gamma-glutamyl transpeptidase, Alkaline phosphatase, conjugated bilirubin)

  at least once a week, during cholestasis

• 1- Other hepatic marker (Aspartate transaminase, alanine transaminase, albumin blood level)

  at least once a week, during cholestasis

• Length required to minimal enteral feeding (120mL/kg/day) measured in days.

  From birth to outcome (usually less than 21 days)

• Weight gain (in g/kg/day)

  From birth to resolution of cholestasis (very varuiable but usually less than 3 months)

• Adverse effects linked to ursodiol

  From beginning to the end of the medication (average 4 weeks)

Study Arms (2)

Ursodiol

EXPERIMENTAL

Participants assigned in this arm receive an ursodiol suspension at 20mg/ml.

Drug: Ursodiol

placebo

PLACEBO COMPARATOR

A placebo suspension that looks like the ursodiol suspension used.

Drug: placebo

Interventions

Ursodiol DRUG

Ursodiol is given by mouth, three times a day from second value of elevated conjugated bilirubin (\>33mmol/L) to the resolution of cholestasis (conjugated bilirubin \<34mmol/L) If Nil per os, 3,3mg/kg/dose is given. If Nil per os is required (e.g. pre-surgery, or necrotizing enterocolitis), none is given. If enteral feeding is under 100mL/kg/day, 6,7 mg/kg/day is given. If enteral feeding exceeds 100mL/kg/day, 10 mg/kg/day is given.

Also known as: Urso, ursodeoxycholic acid

Ursodiol

placebo DRUG

Placebo given in the same amount that ursodiol would be given, depending on enteral feeding and weight. It is also given three times a day, until cholestasis resolution.

placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Preterm or in-term newborns hospitalized in neonatal care units at CHU Sainte-Justine between October 1st 2008 and October 1st 2011.
• Must be receiving parenteral nutrition (either partial or total) at the diagnosis of cholestasis.
• Parental Consent must be obtained.

You may not qualify if:

• Active urinary tract infection
• Presence of clinical signs(acholic stool) of or ultrasound evidence of biliary tract anomalies.
• Positive TORCH infections(Toxoplasmosis, Other infections, Rubella, Cytomegalovirus, Herpes simplex virus)
• Known short bowel syndrome
• Known congenital hypothyroidism
• Known genetic disorders associated with cholestasis like galactosemia, phenylcytonuria, antitrypsin 1 deficiency... etc

Sponsors & Collaborators

• Ibrahim Mohamed: lead

Study Sites (1)

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (5)

• Al-Hathlol K, Al-Madani A, Al-Saif S, Abulaimoun B, Al-Tawil K, El-Demerdash A. Ursodeoxycholic acid therapy for intractable total parenteral nutrition-associated cholestasis in surgical very low birth weight infants. Singapore Med J. 2006 Feb;47(2):147-51.

  PMID: 16435058 BACKGROUND

• Arslanoglu S, Moro GE, Tauschel HD, Boehm G. Ursodeoxycholic acid treatment in preterm infants: a pilot study for the prevention of cholestasis associated with total parenteral nutrition. J Pediatr Gastroenterol Nutr. 2008 Feb;46(2):228-31. doi: 10.1097/MPG.0b013e3181560524.

  PMID: 18223390 BACKGROUND

• Chen CY, Tsao PN, Chen HL, Chou HC, Hsieh WS, Chang MH. Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis. J Pediatr. 2004 Sep;145(3):317-21. doi: 10.1016/j.jpeds.2004.05.038.

  PMID: 15343182 BACKGROUND

• Venigalla S, Gourley GR. Neonatal cholestasis. Semin Perinatol. 2004 Oct;28(5):348-55. doi: 10.1053/j.semperi.2004.09.008.

  PMID: 15686266 BACKGROUND

• McKiernan PJ. Neonatal cholestasis. Semin Neonatol. 2002 Apr;7(2):153-65. doi: 10.1053/siny.2002.0103.

  PMID: 12208100 BACKGROUND

MeSH Terms

Conditions

Cholestasis

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Ibrahim Mohamed, MB ChB, DIS P

  St. Justine's Hospital

  PRINCIPAL INVESTIGATOR

• Josianne Malo, B.Pharm, M.Sc.

  St. Justine's Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assisstant professor of pediatrics

Study Record Dates

• First Submitted: February 17, 2009
• First Posted: February 19, 2009
• Study Start: October 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: March 1, 2013
• Last Updated: September 17, 2013

Record last verified: 2013-09

Locations

CA (1)