Citrin DeficiencyNCT07055269
Liver Metabolic Functions in Patients With Citrin Deficiency and Healthy Subjects
A study testing liver metabolic flux and ureagenesis capacity in people with Citrin Deficiency, run by Johannes Haeberle at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Citrin Deficiency
- What is being tested?
- liver metabolic flux and ureagenesis capacity
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSwitzerland
- Study dates
- 20 Oct 2025to Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of Liver Metabolic Alterations in Vivo in Patients With Citrin Deficiency and Healthy Subjects by Metabolic Labeling With Stable Isotopes
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
- Being tested
- liver metabolic flux, ureagenesis capacity
- Keywords
- Citrin Deficiency, Adolescent and Adult Citrin Deficiency, AACD, SLC25A13, liver metabolic flux, ureagenesis, Citrin
- Medical subject headings
- Adult-onset citrullinemia type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
liver metabolic fluxOther
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 capacityOther
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.
| Study group | Role | What they receive |
|---|---|---|
| AACD patient | Experimental | isotope tracer for ureagenesis and liver metabolic flux Receives: Other: liver metabolic flux; Other: ureagenesis capacity |
| healthy volunteer | Experimental | isotope tracer for ureagenesis and liver metabolic flux Receives: Other: liver metabolic flux |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver metabolic flux
Liver metabolic flux will be measured by assessing the distribution of the administered isotope tracers [U-13C6]-fructose and heavy water.
Measured: 5 days
Secondary outcomes (5)
Ureagenesis capacity
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.
Measured: 1 day
adverse events
Safety and tolerability of 2H2O, [U-13C6]-fructose and 15NH4Cl
Measured: 5 days
liver fat content
Magnetic resonance imaging of the liver for fat content
Measured: 1 day
Liver fibrosis
Ultrasound imaging of the liver to assess fibrosis and cirrhosis
Measured: 1 day
Clinical symptoms
Clinical presentation and fatigue will be measured through questionnaires
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2025
- Study start20 Oct 2025
- Primary completionSep 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Citrin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Cross-sectional observational study, non-randomised
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johannes Haeberle
- Sponsor type
- University, hospital or other
- Collaborators
- Citrin Foundation, Marc Hellerstein, University of Berkeley
- Responsible party
- Sponsor-investigator, Johannes Haeberle, University Children's Hospital, Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07055269
- Sponsor's protocol ID
- 2025-00730
- Other IDs
- 2025
- Status last verified
- Jan 2026
- First submitted
- 25 Jun 2025
- Last updated
- 8 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Liver Metabolic Alterations in Vivo in Patients With Citrin Deficiency and Healthy Subjects by Metabolic Labeling With Stable Isotopes
- ClinicalTrials.gov ID
- NCT07055269
- Acronym / sponsor ID
- 2025-00730
- Conditions
- Citrin Deficiency
- Keywords
- Citrin Deficiency, Adolescent and Adult Citrin Deficiency, AACD, SLC25A13, liver metabolic flux, ureagenesis, Citrin
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Johannes HaeberleUniversity, hospital or other
- Collaborators
- Citrin Foundation, Marc Hellerstein, University of Berkeley
- Study start
- 20 Oct 2025 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 8 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Cross-sectional observational study, non-randomised
| Arm | Type | Receives |
|---|---|---|
| AACD patient | Experimental | Other: liver metabolic flux, Other: ureagenesis capacityisotope tracer for ureagenesis and liver metabolic flux |
| healthy volunteer | Experimental | Other: liver metabolic fluxisotope tracer for ureagenesis and liver metabolic flux |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| liver metabolic fluxAll 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. | Other | AACD patient, healthy volunteer |
| ureagenesis capacityurea 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. | Other | AACD patient |
Primary outcome
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.
5 secondary outcomes
Ureagenesis capacity
Time frame: 1 day
adverse events
Time frame: 5 days
liver fat content
Time frame: 1 day
Liver fibrosis
Time frame: 1 day
Clinical symptoms
Time frame: 1 day
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- Individual participant dataSharing planned: No
Related trials for Citrin Deficiency
RecruitingPhase 1/2
Phase 1/2 Study of KRRO-121 in Healthy Volunteers and Patients With UCD
Urea Cycle Disorders, Inborn, Urea Cycle Disorders
Active, not recruitingObservational study
Multi-omics Study in Citrin Deficiency
Citrin Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing liver metabolic flux and ureagenesis capacity in people with Citrin Deficiency, run by Johannes Haeberle at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver metabolic flux (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.