Comparison of Metabolic Function in the Liver of Healthy Individuals and Those Affected by Citrin Deficiency Disease
Résumé de l'étude
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)
Intervention étudiée
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)
Maladie en cours d'investigation
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)
Critères d'exclusion
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)
Lieu de l’étude
Zurich
(BASEC)
Sponsor
University Children's Hospital Zurich
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Prof. Dr. med. Johannes Häberle
+41 44 249 59 88
Johannes.Haeberle@clutterkispi.uzh.chUniversity Children's Hospital Zurich
(BASEC)
Informations générales
+41 44 249 59 88+41 44 249 59 88
Johannes.Haeberle@clutterkispi.uzh.chJohannes.Haeberle@clutterkispi.uzh.ch(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale de Zurich
(BASEC)
Date d'approbation du comité d'éthique
11.07.2025
(BASEC)
Identifiant de l'essai ICTRP
NCT07055269 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
Assessment of liver metabolic alterations in vivo in patients with citrin deficiency and healthy subjects by metabolic labeling with stable isotopes (BASEC)
Titre académique
Assessment of Liver Metabolic Alterations in Vivo in Patients With Citrin Deficiency and Healthy Subjects by Metabolic Labeling With Stable Isotopes (ICTRP)
Titre public
Liver Metabolic Functions in Patients With Citrin Deficiency and Healthy Subjects (ICTRP)
Maladie en cours d'investigation
Citrin Deficiency (ICTRP)
Intervention étudiée
Other: liver metabolic fluxOther: ureagenesis capacity (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
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 disponible
Critères d'évaluation principaux et secondaires
Liver metabolic flux (ICTRP)
Ureagenesis capacity;adverse events;liver fat content;Liver fibrosis;Clinical symptoms (ICTRP)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
Citrin Foundation;Marc Hellerstein, University of Berkeley (ICTRP)
Contacts supplémentaires
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 secondaires
2025-00730 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT07055269 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible