Nonalcoholic Fatty Liver Disease (NAFLD) Adult Database 2

• ClinicalTrials.gov Identifier: NCT01030484
• Recruitment Status: Completed
• First Posted: December 11, 2009
• Last Update Posted: February 23, 2022
• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Johns Hopkins Bloomberg School of Public Health

Tracking Information

• First Submitted Date: December 10, 2009
• First Posted Date: December 11, 2009
• Last Update Posted Date: February 23, 2022
• Actual Study Start Date: December 2, 2009
• Actual Primary Completion Date: May 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 17, 2013)

Liver histology scores [ Time Frame: varies ]

Liver histology scores (derived from central reading of liver biopsy at entry, standard of care biopsy done during screening or follow-up, or liver biopsy obtained for PIVENS or TONIC trials)

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nonalcoholic Fatty Liver Disease (NAFLD) Adult Database 2
• Official Title: Nonalcoholic Fatty Liver Disease (NAFLD) Adult Database 2
• Brief Summary: The NAFLD Database 2 will recruit at least 1,500 new adult participants suspected or known to have NAFLD or nonalcoholic steatohepatitis (NASH)-related cirrhosis and will also invite adult participants from the prior NAFLD Database and related studies (PIVENS trial and TONIC trial) to enroll in the NAFLD Database 2. To elucidate, through the cooperative effort of a multidisciplinary and multicenter group of collaborators, the etiology, natural history, diagnosis, treatment, and prevention of NAFLD, and in particular its more severe form of NASH and its complications.

Detailed Description

To add to the existing NAFLD Database an additional 1,500 adult participants with a diagnosis of NAFLD, supported by a recent liver biopsy, with a broad range of severity. Core data collection will include clinical, demographic, laboratory, imaging, and histological features

• To increase the population diversity of the NAFLD Database to provide greater representation of Hispanic, Native American, African American, and Asian patients among the new adult participants recruited into the NAFLD Database 2
• To expand the current specimen bank comprised of liver tissue, serum, plasma, and DNA obtained from new participants and continuing participants undergoing repeat liver biopsy with the specific goal of optimizing the collection of plasma or serum suitable for biomarker development studies by obtaining specimens in close temporal proximity to the performance of liver biopsy

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

plasma, serum, liver tissue

• Sampling Method: Non-Probability Sample
• Study Population: adult patients with suspected or known non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH)-related cirrhosis of the liver
• Condition: Liver Disease
• Intervention: Not Provided

Study Groups/Cohorts

NAFLD

adult patients with non-alcoholic fatty liver disease (NAFLD).

Publications *

• Sanyal AJ, Van Natta ML, Clark J, Neuschwander-Tetri BA, Diehl A, Dasarathy S, Loomba R, Chalasani N, Kowdley K, Hameed B, Wilson LA, Yates KP, Belt P, Lazo M, Kleiner DE, Behling C, Tonascia J; NASH Clinical Research Network (CRN). Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease. N Engl J Med. 2021 Oct 21;385(17):1559-1569. doi: 10.1056/NEJMoa2029349.
• Vilar-Gomez E, Gawrieh S, Liang T, McIntyre AD, Hegele RA, Chalasani N. Interrogation of selected genes influencing serum LDL-Cholesterol levels in patients with well characterized NAFLD. J Clin Lipidol. 2021 Mar-Apr;15(2):275-291. doi: 10.1016/j.jacl.2020.12.010. Epub 2020 Dec 27.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 25, 2020): 2501
• Original Estimated Enrollment (submitted: December 10, 2009): 1600
• Actual Study Completion Date: May 31, 2020
• Actual Primary Completion Date: May 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Continuing participants:

• Previously enrolled in the NAFLD Database study, PIVENS or TONIC trials
• Age at least 18 years during the consent process
• Willingness to continue to be followed for up to 4 years
• Ability and willingness to give written, informed consent to be enrolled into Database 2

New participants:

• Age at least 18 years during the consent process
• Willingness to be followed for up to 4 years
• Ability and willingness to give written, informed consent to be screened for and, if eligible, to be enrolled into the Database 2 study
• Minimal or no alcohol use history consistent with NAFLD (see exclusion criteria)
• Collection of a standard of care 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:

• Any condition or circumstances, which, in the opinion of the investigator, would interfere with completion of scheduled follow-up visits and procedures for the duration of the Database 2 study

  • Clinical or histological evidence of alcoholic liver disease: Regular and excessive use of alcohol within the 2 years prior to interview defined as alcohol intake greater than 14 drinks per week in a man or greater than 7 drinks per week in a woman. Approximately 10 g of alcohol equals one 'drink' unit. One unit equals 1 ounce of distilled spirits, one 12-oz beer, or one 4-oz glass of wine
  • 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
  • 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01030484
• Other Study ID Numbers: NAFLD Adult Database 2 (IND); U01DK061730 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Johns Hopkins Bloomberg School of Public Health
• Original Responsible Party: Patricia Robuck, NIDDK
• Current Study Sponsor: Johns Hopkins Bloomberg School of Public Health
• Original Study Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Study Director: Edward Doo, MD; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

• PRS Account: Johns Hopkins Bloomberg School of Public Health
• Verification Date: February 2022