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

This study has been completed.
Sponsor:
Collaborator:
CRS Clinical Research Services Mannheim GmbH
Information provided by (Responsible Party):
Cytonet GmbH & Co. KG
ClinicalTrials.gov Identifier:
NCT01549015
First received: January 16, 2012
Last updated: June 25, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention
Urea Cycle Disorders
Other: oral administration of Sodium [1,2-13C]-Acetate

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

Resource links provided by NLM:


Further study details as provided by Cytonet GmbH & Co. KG:

Primary Outcome Measures:
  • Formation of 13C-urea in plasma [ Time Frame: 0 - 240 Minutes ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Vital signs [ Time Frame: 0-240 min ] [ Designated as safety issue: Yes ]
    blood pressure, heart rate, temperature and respiratory rate at enrollment and after completion

  • Complete blood count without differential [ Time Frame: at enrollement ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: 0-240 mins ] [ Designated as safety issue: Yes ]
  • Ammonia, Amino acids, Urea in serum [ Time Frame: 0-240 min ] [ Designated as safety issue: Yes ]
  • CRP [ Time Frame: at enrollment ] [ Designated as safety issue: Yes ]
  • Venous lactate and blood gases: pH, pCO2, pO2, bicarbonate [ Time Frame: at enrollment ] [ Designated as safety issue: Yes ]
  • Blood glucose [ Time Frame: 0 - 240 min ] [ Designated as safety issue: Yes ]
  • pH and bicarbonate [ Time Frame: 20 and 60 mins after administration ] [ Designated as safety issue: Yes ]

Enrollment: 37
Study Start Date: January 2012
Study Completion Date: March 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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.

  Eligibility

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01549015

Locations
Germany
CRS Clinical Research Services GmbH (Phase I Unit), Mönchengladbach, Germany, 41061
Medizinische Hochschule Hannover, Klinik für Kinderheilkunde
Hannover, Germany, 30625
Universitätsklinikum Heidelberg Klinik für Kinderheilkunde I
Heidelberg, Germany, D-69120
Universitätsklinikum Münster, Zentrum für Kinder- und Jugendmedizin
Münster, Germany, 48149
Sponsors and Collaborators
Cytonet GmbH & Co. KG
CRS Clinical Research Services Mannheim GmbH
Investigators
Principal Investigator: Georg F Hoffmann, Prof Dr med Universitätsklinikum Heidelberg Klinik für Kinderheilkunde I
  More Information

No publications provided

Responsible Party: Cytonet GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT01549015     History of Changes
Other Study ID Numbers: CCD09, 2011-002472-16
Study First Received: January 16, 2012
Last Updated: June 25, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Cytonet GmbH & Co. KG:
Urea Cycle Defects
CPSD
OTCD
ASSD
ASLD

Additional relevant MeSH terms:
Urea Cycle Disorders, Inborn
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases

ClinicalTrials.gov processed this record on July 24, 2014