Prevalence of Liver Disease in Patients Dependent on Parenteral Nutrition (THRIVE-1)

A Prospective Prevalence Study in Adolescent and Adult Patients Dependent on Parenteral Nutrition to Assess the Incidence of Intestinal Failure-Associated Liver Disease

This is a multi-center prospective cross-sectional observational study that will assess the prevalence of liver disease in patients dependent on parenteral nutrition (PN) for 4 or more days per week. Liver disease will be determined by the presence of choline deficiency, cholestasis (confirmed by elevated serum alkaline phosphatase (ALP) liver isoenzyme level), and steatosis (confirmed by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF).

The objective of this study is to investigate the presence/prevalence of liver disease in patients dependent on PN (≥4 days a week).

Study Overview

• Status: Completed
• Conditions: Intestinal Failure-associated Liver Disease

Detailed Description

Eligible participants will provide blood samples at Visit 1 to determine choline deficiency, elevated serum ALP liver isoenzyme level and liver dysfunction, and complete one imaging study (MRI-PDFF) at Visit 1 to assess steatosis.

The purpose of this study is to understand and document critical epidemiological data related to choline deficiency and the incidence of liver disease in patients dependent on PN (≥ 4 days a week) and to better understand this patient population to help determine who might benefit from innovative treatments including IV Choline Chloride treatment.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• Italy
  • Bologna, Italy
    • Center for Chronic Intestinal Failure, St. Orsola Hospital Dept of Medical and Surgical Sciences, University of Bologna
• United Kingdom
  • England
    • Harrow, England, United Kingdom, HA1 3UJ
      • St. Mark's Hospital
    • London, England, United Kingdom, NW1 2BU
      • University College London Hospitals
    • Salford, England, United Kingdom
      • Northern Care Alliance NHS Foundation
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Ronald Reagan Medical Center of UCLA
  • Florida
    • Kissimmee, Florida, United States, 34741
      • IHS Health
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll male and female adults and adolescent participants 12 years and older who are dependent on PN (≥ 4 days a week) in the primary care clinic setting.

Description

Inclusion Criteria:

• The participant and/or their parent/Legally Authorized Representative is willing and able to provide signed informed consent or assent as appropriate
• Male or female adults 18 to 80 years of age, or adolescents 12 to 17 years of age
• Patients dependent on parenteral nutrition (PN) that receive PN for an average ≥ 4 days a week for 10 weeks or longer prior to screening to meet nutritional, caloric, fluid, and/or electrolyte needs
• The Investigator expects no changes in the lipid, dextrose, amino acid, or vitamin regimen to be medically necessary during the participant's participation in the study
• Willingness of participant to maintain his/her current habitual oral diet and fluids regimen for the study duration

Exclusion Criteria:

• Participants taking steatogenic medications for ≥12 weeks in the past 12 months (e.g., amiodarone, tamoxifen, methotrexate, tetracycline, glucocorticoids, anabolic steroids, over the usual dose of estrogen for hormone replacement therapy, and valproate); those taking any medicine (e.g., metformin, thiazolidinediones, ursodeoxycholic acid, pentoxifylline, S-adenosyl-L-Methionine, and betaine) that could affect the measurement of IFALD within 12 weeks prior to study entry
• Participants taking potential hepatotoxic medications that in the judgement of the Investigator is causing hepatic abnormalities
• Participants with a cardiac pacemaker, intravascular stents, other metallic devices, and claustrophobia which are contraindicated to magnetic resonance imaging
• Participants who took choline supplements or choline-containing multivitamins within 14 days of screening
• History of major organ transplant (e.g., heart, kidney, liver, etc.)

For more information on eligibility criteria, please contact the sponsor.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with choline deficiency	Choline deficiency is defined as plasma-free choline concentration less than 7 nmol/mL.	Day 1
Percentage of patients with choline deficiency, elevated serum ALP liver isoenzyme level and MRI-PDFF ≥8%	Choline deficiency is defined as plasma-free choline concentration less than 7 nmol/mL. Elevated serum ALP liver isoenzyme level is defined as >1.5x upper limit of normal. MRI-PDFF ≥8 %	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with MRI-PDFF ≥8%	Assessment of liver tests all patients and patients with choline deficiency. Choline deficiency is defined as plasma-free choline concentration less than 7 nmol/mL;	Day 1
Percentage of patients with elevated serum ALP liver isoenzyme level (defined as ≥ 1.5x upper limit of normal)	Assessment of liver tests all patients and patients with choline deficiency. Choline deficiency is defined as plasma-free choline concentration less than 7 nmol/mL;	Day 1
Percentage of patients with abnormal liver tests including serum direct bilirubin, AST, ALT and GGT	Assessment of liver tests all patients and patients with choline deficiency. Choline deficiency is defined as plasma-free choline concentration less than 7 nmol/mL; AST = aspartate aminotransferase; ALT = alanine transaminase; GGT = gamma-glutamyl transferase.	Day 1

Collaborators and Investigators

• Sponsor: Protara Therapeutics
• Investigators: Study Director: Chief Scientific Operations Officer, Protara Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2021
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: August 11, 2021
• First Posted (Actual): August 18, 2021

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Hepatic steatosis; Liver disease; Cholestasis; Parenteral nutrition; Intestinal failure-associated liver disease (IFALD); IFALD; Choline deficiency; parenteral nutrition-associated liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Liver Diseases; Intestinal Failure
• Other Study ID Numbers: TARA-001-502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No