Clinical trial NCT05011370: Prevalence of Liver Disease in Patients Dependent on Parenteral Nutrition
Official title: A Prospective Prevalence Study in Adolescent and Adult Patients Dependent on Parenteral Nutrition to Assess the Incidence of Intestinal Failure-Associated Liver Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Intestinal Failure-associated Liver Disease
Keywords: Intestinal failure-associated liver disease (IFALD)
IFALD
Liver disease
Parenteral nutrition
Choline deficiency
Hepatic steatosis
Cholestasis
parenteral nutrition-associated liver disease
Lead sponsor: Protara Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-08-18
Enrollment: 80
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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 outcomes:
measure: Percentage of patients with choline deficiency
timeFrame: Day 1
measure: Percentage of patients with choline deficiency, elevated serum ALP liver isoenzyme level and MRI-PDFF ≥8%
timeFrame: Day 1
Secondary outcomes:
measure: Percentage of patients with MRI-PDFF ≥8%
timeFrame: Day 1
measure: Percentage of patients with elevated serum ALP liver isoenzyme level (defined as ≥ 1.5x upper limit of normal)
timeFrame: Day 1
measure: Percentage of patients with abnormal liver tests including serum direct bilirubin, AST, ALT and GGT
timeFrame: Day 1
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan Medical Center of UCLA
state: California
city: Kissimmee
country: United States
facility: IHS Health
state: Florida
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Bologna
country: Italy
facility: Center for Chronic Intestinal Failure, St. Orsola Hospital Dept of Medical and Surgical Sciences, University of Bologna
city: Harrow
country: United Kingdom
facility: St. Mark's Hospital
state: England
city: London
country: United Kingdom
facility: University College London Hospitals
state: England
city: Salford
country: United Kingdom
facility: Northern Care Alliance NHS Foundation
state: England
Study officials:
affiliation: Protara Therapeutics
name: Chief Scientific Operations Officer
role: STUDY_DIRECTOR
References: