1. Healthy subjects 2. Symptomatic UCD patients with genetically confirmed CPSD, OTCD, ASSD, or ASLD 3. Asymptomatic carriers of UCD mutations (e.g. parents) MedDRA version: 14.0 Level: LLT Classification code 10013373 Term: Disorders of urea cycle metabolism System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: Sodium [1,2-13C]-Acetate
Product Code: Sodium [1,2-13C]-Acetate
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: Sodium (1,2-13C) acetate
CAS Number: 56374-56-2
Curre
Sponsors
Cytonet GmbH & Co KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All study groups: • Written informed consent given by subjects or his/her parents/legal guardians who are able to understand and follow instructions related to the study Group 1: • Age: 18 - 65 years • Healthy subjects • No clinical or laboratory parameter outside normal ranges at screening and judged as clinically relevant by the investigator Group 2: Age: 0 - 65 years • Symptomatic subjects with genetically confirmed • Carbamylphosphate synthetase I Deficiency [CPSD] • Ornithine Transcarbamylase Deficiency [OTCD] • Argininosuccinate Synthetase Deficiency [Citrullinaemia type I] • Argininosuccinate Lyase Deficiency [ASLD] • at least 1 metabolic decompensation with clinical signs ofhyperammonemia in medical history or genetically confirmed and prospectively treated siblings of symptomatic patients, even without clinical symptoms • Confirmed diagnosis and medical history available (in particular number and severity of metabolic crises) Group 3: • Age: 0 - 65 years • Asymptomatic carriers of mutations for • Carbamylphosphate synthetase I Deficiency [CPSD] • Ornithine Transcarbamylase Deficiency [OTCD] • Argininosuccinate Synthetase Deficiency [Citrullinaemia type 1] • Argininosuccinate Lyase Deficiency [ASLD] • no dietary protein restriction, no intake of ammonia scavenging drugs, no known metabolic decompensation with clinical signs of hyperammonemia Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Acute illness, including vomiting, fever or other sign of infection • Participation in other invasive clinical trials within 30 days prior to inclusion • Liver or renal disease • Acute seizures • Coma • Bleeding disorder • Blood ammonia > 100 µmol/l for patients with a urea cycle disorder and blood ammonia > normal for healthy probands and asymptomatic carriers • Metabolic acidosis • Pregnancy or lactation • Body weight < 8 kg
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To investigate the performance of the urea cycle in healthy subjects, patients with urea cycle disorders (UCD), and carriers of UCD mutations by use of the 13C-ureagenesis assay. • To compare the performance of the urea cycle with respect to the genotype and to the clinical phenotype.;Secondary Objective: ;Primary end point(s): Formation of 13C-urea in plasma | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Diagnostic variables (to be assessed retrospectively in UCD subjects) • Laboratory parameters: all ammonia and glutamine levels in plasma (in history) • History of protein intake (if applicable) • Nutritional status (in history) • DNA mutation (at study entry or after evaluation for patients that do not provide such data already) • Number, duration and severity of metabolic crises (e.g. number of hospitalizations due to crises, maximal ammonia concentration and duration of ammonia elevation, coma yes/no) (in history) • Use of ammonia scavenging drugs (in history) • Intake of arginine, citrulline (apart from ASSD) and amino acid mixture (in history) • Neurological status (in history) Safety and metabolic variables (to be assessed in all subjects): • Vital signs (blood pressure, heart rate, temperature and respiratory rate at enrollment and after completion) • Complete blood count without differential (immediately after enrollment) • Adverse events • Ammonia, Amino acids (immediately after enrollment, 0 min), Urea in serum (only 0 min) • CRP (immediately after enrollment) • Venous lactate and blood gases: pH, pCO2, pO2, bicarbonate (immediately after enrollment) • Blood glucose (immediately after enrollment and hourly during the 13C assay) | — |
Countries
Germany
Contacts
Public ContactClinical Study Manager
Cytonet GmbH & Co KG
Outcome results
None listed