Prevalence of Liver Disease in Patients Dependent on Parenteral Nutrition

Completed

Brief Summary: 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).

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.

Recruitment & Eligibility

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.

Primary Outcome Measures

Name	Time	Method
Percentage of patients with choline deficiency, elevated serum ALP liver isoenzyme level and MRI-PDFF ≥8%	Day 1	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 %
Percentage of patients with choline deficiency	Day 1	Choline deficiency is defined as plasma-free choline concentration less than 7 nmol/mL.

Secondary Outcome Measures

Name	Time	Method
Percentage of patients with elevated serum ALP liver isoenzyme level (defined as ≥ 1.5x upper limit of normal)	Day 1	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;
Percentage of patients with MRI-PDFF ≥8%	Day 1	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;
Percentage of patients with abnormal liver tests including serum direct bilirubin, AST, ALT and GGT	Day 1	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.

Locations (15): IHS Health
🇺🇸
Kissimmee, Florida, United States
The University of Chicago
🇺🇸
Chicago, Illinois, United States
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States
Rigshospitalet
🇩🇰
Copenhagen, Denmark
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Ronald Reagan Medical Center of UCLA
🇺🇸
Los Angeles, California, United States
Seattle Children's
🇺🇸
Seattle, Washington, United States
St. Mark's Hospital
🇬🇧
Harrow, England, United Kingdom
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Cincinnati Children's Hospital
🇺🇸
Cincinnati, Ohio, United States
UPMC Children's Hospital of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
University College London Hospitals
🇬🇧
London, England, United Kingdom
Center for Chronic Intestinal Failure, St. Orsola Hospital Dept of Medical and Surgical Sciences, University of Bologna
🇮🇹
Bologna, Italy
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Northern Care Alliance NHS Foundation
🇬🇧
Salford, England, United Kingdom