Clinical trial NCT01061684: NAFLD Pediatric Database 2
Official title: Nonalcoholic Fatty Liver Disease (NAFLD) Pediatric Database 2
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Disease
Keywords: fatty liver disease
NASH
NAFLD
non-alcoholic steatohepatitis
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2010-02-03
Enrollment: 969
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants at least 2 years of age and less than 18 years of age with known or suspected NAFLD or NASH-related cirrhosis

Brief summary: The NAFLD Database 2 will recruit at least 650 new pediatric participants with liver biopsies and contemporaneous biosamples, and will also invite pediatric participants from the prior NAFLD Database and TONIC trial (50 with a recent biopsy and 150 without a contemporaneous biopsy) to enroll in the NAFLD Pediatric Database 2 study. Combining the new and continuing participants leads to a recruitment goal for the pediatric Database 2 of 850 pediatric participants during the enrollment period.

Detailed description: All the new pediatric participants will have had a liver biopsy within 120 days prior to enrollment coupled with contemporaneous biosamples within 90 days prior to enrollment and up to 90 days before or 4-90 days after the biopsy. We estimate that at least 50 of the continuing pediatric participants will be due for a standard of care liver biopsy at the time of their enrollment into the pediatric Database 2 study, and will, as a result, also have a liver biopsy and contemporaneous biosamples.

Eligibility criteria: Inclusion Criteria:

* Continuing participants:

  * Previously enrolled in the NAFLD Database study or TONIC trial
  * Age at least 2 years and not older than 17 years during the consent process
  * Willingness to continue to be followed for up to 4 years
  * Ability and willingness to give written, informed parental consent and child assent, per local IRB guidelines, to be enrolled into the pediatric Database 2 study
* New participants:

  * Age at least 2 years of age and not older than 17 years during the consent process
  * Willingness to be followed for up to 4 years
  * Ability and willingness to give written, informed parent consent and child assent to be enrolled into the pediatric Database 2 study
  * Minimal or no alcohol use history consistent with NAFLD
  * Having undergone a liver biopsy that is obtained within 120 days of enrollment
  * Collection of biosamples (serum, plasma, DNA, and, if available, liver tissue) within 90 days prior to enrollment and 0-90 days before or 4-90 days after the standard of care liver biopsy

Exclusion Criteria:

* Total parenteral nutrition for more than 1 month within a 6 month period before baseline liver biopsy
* Short bowel syndrome
* History of gastric or jejunoileal bypass preceding the diagnosis of NAFLD. Bariatric surgery performed following enrollment is not exclusionary. Liver biopsies obtained during bariatric surgery cannot be used for enrollment because of the associated surgical or anesthetic acute changes and the weight loss efforts that precede bariatric surgery
* History of biliopancreatic diversion
* Evidence of advanced liver disease defined as a Child-Pugh-Turcotte score equal to or greater than 10
* Evidence of chronic hepatitis B as marked by the presence of HBsAg in serum (participants with isolated antibody to hepatitis B core antigen, anti-HBc total, are not excluded)
* Evidence of chronic hepatitis C as marked by the presence of anti-HCV or HCV RNA in serum
* Low alpha-1-antitrypsin level and ZZ phenotype (both determined at the discretion of the investigator)
* Wilson's disease
* Known glycogen storage disease
* Known dysbetalipoproteinemia
* Known phenotypic hemochromatosis (HII greater than 1.9 or removal of more than 4 g of iron by phlebotomy)
* Prominent bile duct injury (florid duct lesions or periductal sclerosis) or bile duct paucity
* Chronic cholestasis
* Vascular lesions (vasculitis, cardiac sclerosis, acute or chronic Budd-Chiari, hepatoportal sclerosis, peliosis)
* Iron overload greater than 3+
* Zones of confluent necrosis, infarction, massive or sub-massive, pan-acinar necrosis
* Multiple epithelioid granulomas
* Congenital hepatic fibrosis
* Cystic fibrosis
* Polycystic liver disease
* Other metabolic or congenital liver disease
* Evidence of systemic infectious disease
* Known HIV positive
* Disseminated or advanced malignancy
* Concomitant severe underlying systemic illness that in the opinion of the investigator would interfere with completion of follow-up
* Active drug use or dependence that, in the opinion of the study investigator, would interfere with adherence to study requirements
* Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of study
* Inability for parent to provide informed consent and child 8 years or greater to give assent

Primary outcomes:
measure: Liver histology scores
timeFrame: varies
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago (NWU)
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Buffalo
country: United States
facility: University at Buffalo-Women and Children's Hospital of Buffalo
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital- UW
state: Washington
Study officials:
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Ed Doo, MD
role: STUDY_DIRECTOR
References:
citation: Rausch JC, Lavine JE, Chalasani N, Guo X, Kwon S, Schwimmer JB, Molleston JP, Loomba R, Brunt EM, Chen YI, Goodarzi MO, Taylor KD, Yates KP, Rotter JI; NASH Clinical Research Network. Genetic Variants Associated With Obesity and Insulin Resistance in Hispanic Boys With Nonalcoholic Fatty Liver Disease. J Pediatr Gastroenterol Nutr. 2018 May;66(5):789-796. doi: 10.1097/MPG.0000000000001926.
citation: Molleston JP, Schwimmer JB, Yates KP, Murray KF, Cummings OW, Lavine JE, Brunt EM, Scheimann AO, Unalp-Arida A; NASH Clinical Research Network. Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels. J Pediatr. 2014 Apr;164(4):707-713.e3. doi: 10.1016/j.jpeds.2013.10.071. Epub 2013 Dec 19.