Urea Cycle Disorders
Conditions
Keywords
Urea Cycle Defects, CPSD, OTCD, ASSD, ASLD
Brief summary
This diagnostic study will be performed to investigate the performance of the urea cycle in healthy subjects, asymptomatic carriers of Urea Cycle Disorders (UCD) mutations and subjects with genetically proven urea cycle disorders. The ureagenesis rate will be measured by 13C incorporation assay, a method for in vivo measurement of urea cycle performance with stable isotopes.
Detailed description
In this diagnostic study CCD09, the urea metabolism in UCD subjects (patients and carriers) and healthy subjects of different age and sex will be assessed by measurement of the incorporation of 13C from orally taken sodium \[1,2-13C\]-acetate into urea by 13C stable isotope ratio detection. The aim of the study is to determine the 13C urea production and to quantify the total urea production in healthy subject, gene defect carrier or patient as marker for the functioning of the urea cycle. Since there are still only few data available using this specific method for measurement of urea cycle performance, the aim of this study CCD09 is to gain additional results on the 13C assay. To this end, comparison will be made between 13C urea production observed in healthy subjects, UCD patients, and asymptomatic mutation carriers. An evaluation of this study may also enable the treating physician to better judge the severity of disease and the future risk of metabolic decompensations in patients as well as the potential risk for so far asymptomatic carriers.
Interventions
OTHERoral administration of Sodium [1,2-13C]-Acetate
single dose of 0.55 mg/kg 13C-Acetate given orally of via a naso-gastric tube
Sponsors
CRS Clinical Research Services Mannheim GmbH
Cytonet GmbH & Co. KG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 65 Years
Healthy volunteers
Yes
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 Healthy Volunteers: * 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 Symptomatic UCD patients with genetically confirmed CPSD, OTCD, ASSD, or ASLD: 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 of hyperammonemia 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 Asymptomatic carriers of UCD mutations: * 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 Group 4: * Infants between 8 - 10 kg body weight 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 of hyperammonemia 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
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 \< 8kg * Chronic somatic or psychiatric disease not related to UCD
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Formation of 13C-urea in plasma | 0 - 240 Minutes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood glucose | 0 - 240 min | — |
| Vital signs | 0-240 min | blood pressure, heart rate, temperature and respiratory rate at enrollment and after completion |
| Complete blood count without differential | at enrollement | — |
| Venous lactate and blood gases: pH, pCO2, pO2, bicarbonate | at enrollment | — |
| Ammonia, Amino acids, Urea in serum | 0-240 min | — |
| CRP | at enrollment | — |
| pH and bicarbonate | 20 and 60 mins after administration | — |
| Adverse events | 0-240 mins | — |
Countries
Germany
Outcome results
None listed