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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01549015
Other study ID # CCD09
Secondary ID 2011-002472-16
Status Completed
Phase N/A
First received January 16, 2012
Last updated June 25, 2013
Start date January 2012
Est. completion date March 2013

Study information

Verified date June 2013
Source Cytonet GmbH & Co. KG
Contact n/a
Is FDA regulated No
Health authority Germany: Federal Institute for Drugs and Medical Devices
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 37
Est. completion date March 2013
Est. primary completion date July 2012
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group N/A to 65 Years
Eligibility 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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic


Related Conditions & MeSH terms


Intervention

Other:
oral administration of Sodium [1,2-13C]-Acetate
single dose of 0.55 mg/kg 13C-Acetate given orally of via a naso-gastric tube

Locations

Country Name City State
Germany Medizinische Hochschule Hannover, Klinik für Kinderheilkunde Hannover
Germany Universitätsklinikum Heidelberg Klinik für Kinderheilkunde I Heidelberg
Germany Universitätsklinikum Münster, Zentrum für Kinder- und Jugendmedizin Münster

Sponsors (2)

Lead Sponsor Collaborator
Cytonet GmbH & Co. KG CRS Clinical Research Services Mannheim GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Formation of 13C-urea in plasma 0 - 240 Minutes No
Secondary Vital signs blood pressure, heart rate, temperature and respiratory rate at enrollment and after completion 0-240 min Yes
Secondary Complete blood count without differential at enrollement Yes
Secondary Adverse events 0-240 mins Yes
Secondary Ammonia, Amino acids, Urea in serum 0-240 min Yes
Secondary CRP at enrollment Yes
Secondary Venous lactate and blood gases: pH, pCO2, pO2, bicarbonate at enrollment Yes
Secondary Blood glucose 0 - 240 min Yes
Secondary pH and bicarbonate 20 and 60 mins after administration Yes
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