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NCT07055269 | RECRUITING | Citrin Deficiency

Liver Metabolic Functions in Patients With Citrin Deficiency and Healthy Subjects
Sponsor:

John Haeberle

Information provided by (Responsible Party):

John Haeberle

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.

Condition or disease

Citrin Deficiency

Intervention/treatment

liver metabolic flux

ureagenesis capacity

Phase

NA

Study Type : INTERVENTIONAL
Estimated Enrollment : 20 participants
Masking : NONE
Primary Purpose : BASIC_SCIENCE
Official Title : Assessment of Liver Metabolic Alterations in Vivo in Patients With Citrin Deficiency and Healthy Subjects by Metabolic Labeling With Stable Isotopes
Actual Study Start Date : 2025-10-20
Estimated Primary Completion Date : 2026-09
Estimated Study Completion Date : 2026-09

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years to 65 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers: 1
Criteria
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
Liver Metabolic Functions in Patients With Citrin Deficiency and Healthy Subjects

Location Details

NCT07055269

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Locations

RECRUITING

Switzerland,

University Children's Hospital Zurich

Zurich, Switzerland, 8008