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Active, not recruiting

NCT Number: NCT07055269

Liver Metabolic Functions in Patients With Citrin Deficiency and Healthy Subjects

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.

Active, not recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Citrin Deficiency Adult-onset citrullinemia type 2

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Children's Hospital Zurich

Zurich, 8008, Switzerland

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

liver metabolic flux

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

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.

Primary outcomes

  1. Liver metabolic flux

    Time frame: 5 days

    Liver metabolic flux will be measured by assessing the distribution of the administered isotope tracers [U-13C6]-fructose and heavy water.

Secondary outcomes

  1. Ureagenesis capacity

    Time frame: 1 day

    Patients will receive an oral dose of 2 mg/kg of the 15NH4Cl tracer diluted in water. Blood will be collected at various time points up to 2 hours after tracer administration to assess the body's ability to remove ammonia.

  2. adverse events

    Time frame: 5 days

    Safety and tolerability of 2H2O, [U-13C6]-fructose and 15NH4Cl

  3. liver fat content

    Time frame: 1 day

    Magnetic resonance imaging of the liver for fat content

  4. Liver fibrosis

    Time frame: 1 day

    Ultrasound imaging of the liver to assess fibrosis and cirrhosis

  5. Clinical symptoms

    Time frame: 1 day

    Clinical presentation and fatigue will be measured through questionnaires

Sponsors and collaborators

Lead sponsor

Johannes Haeberle

Other

Collaborators

  • Citrin Foundation
  • Marc Hellerstein, University of Berkeley

Registry information

Official study title

Assessment of Liver Metabolic Alterations in Vivo in Patients With Citrin Deficiency and Healthy Subjects by Metabolic Labeling With Stable Isotopes

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Jul 8, 2025
Registry last updated
Jan 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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