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

NCT01549015 | Completed

• 2 other identifiers: CCD092011-002472-16
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 4

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.

Conditions

Urea Cycle Disorders

Keywords

Urea Cycle Defects; CPSD; OTCD; ASSD; ASLD

Outcome Measures

Primary Outcomes (1)

• Formation of 13C-urea in plasma

  0 - 240 Minutes

Secondary Outcomes (8)

• Vital signs

  0-240 min

• Complete blood count without differential

  at enrollement

• Adverse events

  0-240 mins

• Ammonia, Amino acids, Urea in serum

  0-240 min

• CRP

  at enrollment

Interventions

oral administration of Sodium [1,2-13C]-Acetate OTHER

single dose of 0.55 mg/kg 13C-Acetate given orally of via a naso-gastric tube

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• Acute illness, including vomiting, fever or other sign of infection
• 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

Sponsors & Collaborators

• Cytonet GmbH & Co. KG: lead
• CRS Clinical Research Services Mannheim GmbH: collaborator

Study Sites (4)

Unknown Facility

CRS Clinical Research Services GmbH (Phase I Unit), Mönchengladbach, 41061, Germany

Location

Medizinische Hochschule Hannover, Klinik für Kinderheilkunde

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg Klinik für Kinderheilkunde I

Heidelberg, D-69120, Germany

Location

Universitätsklinikum Münster, Zentrum für Kinder- und Jugendmedizin

Münster, 48149, Germany

Location

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Georg F Hoffmann, Prof Dr med

  Universitätsklinikum Heidelberg Klinik für Kinderheilkunde I

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2012
• First Posted: March 8, 2012
• Study Start: January 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: March 1, 2013
• Last Updated: June 26, 2013

Record last verified: 2013-06

Locations

DE (4)