Study in Healthy Subjects, Patients With Urea Cycle Disorders (UCD) and Carriers of UCD Mutations to Evaluate Urea Cycle Function

Urea Cycle Disorders Clinical Trial

Official title:

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

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

• Urea Cycle Disorders
• Urea Cycle Disorders, Inborn

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