Liver Metabolic Functions in Patients With Citrin Deficiency and Healthy Subjects

Last updated: January 5, 2026
Sponsor: Johannes Haeberle
Overall Status: Active - Not Recruiting

Phase

N/A

Condition

Urea Cycle Disorder

Treatment

ureagenesis capacity

liver metabolic flux

Clinical Study ID

NCT07055269
2025-00730
  • Ages 18-65
  • All Genders
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Inclusion criteria for AACD patients are:

  • 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

Inclusion criteria for healthy subjects are:

  • 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 for AACD patients are:

  • 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

Exclusion criteria for healthy subjects are:

  • 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

Study Design

Total Participants: 20
Treatment Group(s): 2
Primary Treatment: ureagenesis capacity
Phase:
Study Start date:
October 20, 2025
Estimated Completion Date:
September 30, 2026

Connect with a study center

  • University Children's Hospital Zurich

    Zurich, 8008
    Switzerland

    Site Not Available

  • University Children's Hospital Zurich

    Zurich 2657896, 8008
    Switzerland

    Site Not Available

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