Comparison of Metabolic Function in the Liver of Healthy Individuals and Those Affected by Citrin Deficiency Disease
Descrizione riassuntiva dello studio
In this study, we investigate whether the main metabolic functions of the liver are impaired in Citrin deficiency. Additionally, the body's ability to remove ammonia (the so-called urea cycle capacity) is assessed. • Group 1 (Patients) a) Undergoes a urea capacity test, in which participants are orally administered the isotope tracer 15NH4Cl. Blood is drawn before and at intervals up to two hours after isotope administration; the total blood volume collected is approximately 6 mL. b) Completing a clinical questionnaire and a fatigue assessment. c) Undergoes a liver metabolism flow test, where participants are orally administered the isotope tracer 2H2O for five days. On the sixth day, [U-13C6]-Fructose is also administered orally, and blood is drawn twice more to investigate liver metabolic function. The total blood volume required and collected for the test is approximately 36 mL. Participants are asked to maintain a dietary diary in the form of photos of their meals throughout the study. d) Participants also undergo a liver MRI and an ultrasound examination to assess liver fat content, fibrosis, and cirrhosis. • Group 2 (Healthy Control) a) Undergoes a liver metabolism flow test, where participants are orally administered the isotope tracer 2H2O for five days and on the fifth day [U-13C6]-Fructose, followed by two blood draws on the fifth day to investigate liver metabolic function. The total blood volume collected for this test is approximately 36 mL. Participants are asked to maintain a dietary diary in the form of photos of their meals throughout the study. No liver MRI or ultrasound examination is performed on healthy controls.
(BASEC)
Intervento studiato
Our intervention follows a protocol that includes the administration of water (2H2O, known as 'heavy water') and [U-13C6]-Fructose with isotopic labeling to conduct a metabolic flow test. Additionally, isotopically labeled ammonium chloride (15NH4Cl) is diluted in water and consumed to assess how well ammonia is excreted.
(BASEC)
Malattie studiate
Citrin Deficiency Disease
(BASEC)
1) Adults of both sexes aged 18 to 65 years. 2) Participants in the patient group must have genetically confirmed Citrin deficiency. 3) Participants in the control group should be demographically similar to the patient group. (BASEC)
Criteri di esclusione
1) Presence of another treatable disease. 2) Use of medications that may impair liver function. 3) Presence of genetic variants in both alleles of the Citrin gene (only for the control group). (BASEC)
Luogo dello studio
Zurigo
(BASEC)
Sponsor
University Children's Hospital Zurich
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Prof. Dr. med. Johannes Häberle
+41 44 249 59 88
Johannes.Haeberle@clutterkispi.uzh.chUniversity Children's Hospital Zurich
(BASEC)
Informazioni generali
+41 44 249 59 88+41 44 249 59 88
Johannes.Haeberle@clutterkispi.uzh.chJohannes.Haeberle@clutterkispi.uzh.ch(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione etica Zurigo
(BASEC)
Data di approvazione del comitato etico
11.07.2025
(BASEC)
ID di studio ICTRP
NCT07055269 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
Assessment of liver metabolic alterations in vivo in patients with citrin deficiency and healthy subjects by metabolic labeling with stable isotopes (BASEC)
Titolo accademico
Assessment of Liver Metabolic Alterations in Vivo in Patients With Citrin Deficiency and Healthy Subjects by Metabolic Labeling With Stable Isotopes (ICTRP)
Titolo pubblico
Liver Metabolic Functions in Patients With Citrin Deficiency and Healthy Subjects (ICTRP)
Malattie studiate
Citrin Deficiency (ICTRP)
Intervento studiato
Other: liver metabolic fluxOther: ureagenesis capacity (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: None (Open Label). (ICTRP)
Criteri di inclusione/esclusione
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 (ICTRP)
non disponibile
Endpoint primari e secondari
Liver metabolic flux (ICTRP)
Ureagenesis capacity;adverse events;liver fat content;Liver fibrosis;Clinical symptoms (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
Citrin Foundation;Marc Hellerstein, University of Berkeley (ICTRP)
Contatti aggiuntivi
Johannes Hberle, Prof. Dr. med.Johannes Hberle, Prof. Dr. med., Johannes.Haeberle@kispi.uzh.chJohannes.Haeberle@kispi.uzh.ch, +41 44 249 59 88+41 44 249 59 88 (ICTRP)
ID secondari
2025-00730 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT07055269 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile