Open, prospective, diagnostic, multicentre study in healthy subjects, patients with urea cycle disorders (UCD), and carriers of UCD mutations, to evaluate in vivo ureagenesis measured after a single application of Sodium [1,2-13C]-Acetate

Conditions: 1. Healthy subjects2. Symptomatic UCD patients with genetically confirmedCPSD, OTCD, ASSD, or ASLD3. Asymptomatic carriers of UCD mutations (e.g. parents)
MedDRA version: 14.0Level: LLTClassification code 10013373Term: Disorders of urea cycle metabolismSystem Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2011-002472-16-DE

Lead Sponsor: Cytonet GmbH & Co KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

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

• 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To investigate the performance of the urea cycle in healthy subjects,<br>patients with urea cycle disorders (UCD), and carriers of UCD mutations<br>by use of the 13C-ureagenesis assay.<br>• To compare the performance of the urea cycle with respect to the<br>genotype and to the clinical phenotype.;Secondary Objective: ;Primary end point(s): Formation of 13C-urea in plasma

Secondary Outcome Measures