Liver Metabolic Functions in Patients With Citrin Deficiency and Healthy Subjects

NCT ID: NCT07055269

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-20
• Study Completion Date: 2026-09-30

Brief Summary

Citrin is an aspartate-glutamate transporter in the liver that facilitates the urea cycle pathway for ammonia detoxification via ureagenesis. It is also thought to be involved in liver energy metabolism as a component of the malate-aspartate shuttle. The clinical presentation in patients supports the hypothesis that liver glycolytic, gluconeogenic and lipogenic functions are compromised in citrin deficiency, but none of the key hepatic pathway fluxes have been measured in patients to date. This is the first study that will examine the liver metabolic fluxes in patients with citrin deficiency.

Liver metabolic functions will be examined by metabolic flux assays and biochemical measurements after application of stable isotopes 2H2O and [U-13C6]-fructose. Urea cycle metabolites and their enrichment after application of a stable isotope tracer 15NH4Cl will be measured to examine the liver's ability to detoxify ammonia into urea.

Conditions

Citrin Deficiency

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

AACD patient

isotope tracer for ureagenesis and liver metabolic flux

Group Type: EXPERIMENTAL

liver metabolic flux

Intervention Type: OTHER

All participants will be given heavy water (2H2O, deuterium-labelled) and \[U-13C6\]-fructose orally, each followed by the collection of one blood plasma sample. Additional biochemical and clinical parameters including liver fat content by MRI, liver fibrosis and cirrhosis by ultrasound imaging and plasma biochemical profiles will be analyzed.

ureagenesis capacity

Intervention Type: OTHER

urea and urea cycle metabolites and their enrichment after oral administration of a stable isotope tracer 15NH4Cl will be measured to examine the liver's ability to detoxify ammonia.

healthy volunteer

isotope tracer for ureagenesis and liver metabolic flux

Group Type: EXPERIMENTAL

liver metabolic flux

Intervention Type: OTHER

All participants will be given heavy water (2H2O, deuterium-labelled) and \[U-13C6\]-fructose orally, each followed by the collection of one blood plasma sample. Additional biochemical and clinical parameters including liver fat content by MRI, liver fibrosis and cirrhosis by ultrasound imaging and plasma biochemical profiles will be analyzed.

Interventions

liver metabolic flux

All participants will be given heavy water (2H2O, deuterium-labelled) and \[U-13C6\]-fructose orally, each followed by the collection of one blood plasma sample. Additional biochemical and clinical parameters including liver fat content by MRI, liver fibrosis and cirrhosis by ultrasound imaging and plasma biochemical profiles will be analyzed.

Intervention Type: OTHER

ureagenesis capacity

urea and urea cycle metabolites and their enrichment after oral administration of a stable isotope tracer 15NH4Cl will be measured to examine the liver's ability to detoxify ammonia.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Subjects with citrin deficiency, confirmed by genetic analysis to carry pathogenic variant(s) in the SLC25A13 gene
• Age from 18 years to 65 years inclusive
• Male or female
• Written informed consent has been given
• Understands and is willing, able and likely to comply with study procedures and restrictions

• Age from 18 years to 65 years inclusive, and not more than five years younger or older than the specified paired participant from the AACD group
• Same sex as the specified paired participant from the AACD group
• Same ethnicity the specified paired participant from the AACD group
• Written informed consent has been given
• Understands and is willing, able and likely to comply with study procedures and restrictions

Exclusion Criteria

• acute and chronic disease requiring treatment of any kind, other than his/her AACD
• females who are pregnant or lactating or attempting to become pregnant
• use of any medication which, in the opinion of the investigator, is likely to interfere with liver function

• carry any pathogenic variant in the SLC25A13 gene
• current or recurrent disease that could affect the metabolic function of the liver
• acute and chronic disease requiring treatment of any kind
• females who are pregnant or lactating or attempting to become pregnant
• use of any medication which, in the opinion of the investigator, is likely to interfere with liver function
• weight loss ≥10% within 3 months before study screening
• daily alcohol consumption of more than 2 standard-sized beer for men and more than 1 standard-sized beer for women, or the equivalent
• BMI > 30 kg/m2
• currently smoking >1 cigarette daily
• liver transplant recipients
• type 1 and 2 diabetes
• currently on a ketogenic diet
• currently taking medium chain triglyceride (MCT) supplements

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Citrin Foundation

UNKNOWN

Sponsor Role: collaborator

Marc Hellerstein, University of Berkeley

UNKNOWN

Sponsor Role: collaborator

Johannes Haeberle

OTHER

Sponsor Role: lead

Responsible Party

Johannes Haeberle

Head of Metabolic Laboratory

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

University Children's Hospital Zurich

Zurich, , Switzerland

Countries

Switzerland

Other Identifiers

2025-00730

Identifier Type: -

Identifier Source: org_study_id