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

Primary Purpose

Urea Cycle Disorders

Status

Completed

Phase

Not Applicable

Locations

Germany

Study Type

Interventional

Intervention

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

About this trial

This is an interventional diagnostic trial for Urea Cycle Disorders focused on measuring Urea Cycle Defects, CPSD, OTCD, ASSD, ASLD

Eligibility Criteria

undefined - 65 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Medizinische Hochschule Hannover, Klinik für Kinderheilkunde
Universitätsklinikum Heidelberg Klinik für Kinderheilkunde I
Universitätsklinikum Münster, Zentrum für Kinder- und Jugendmedizin

Outcomes

Primary Outcome Measures

Formation of 13C-urea in plasma

Secondary Outcome Measures

Vital signs

blood pressure, heart rate, temperature and respiratory rate at enrollment and after completion

Complete blood count without differential

Adverse events

Ammonia, Amino acids, Urea in serum

CRP

Venous lactate and blood gases: pH, pCO2, pO2, bicarbonate

Blood glucose

pH and bicarbonate

Full Information

NCT ID

NCT01549015

First Posted

January 16, 2012

Last Updated

June 25, 2013

Sponsor

Cytonet GmbH & Co. KG

Collaborators

CRS Clinical Research Services Mannheim GmbH

1. Study Identification

Unique Protocol Identification Number

NCT01549015

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2013

Overall Recruitment Status

Completed

Study Start Date

January 2012 (undefined)

Primary Completion Date

July 2012 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cytonet GmbH & Co. KG

Collaborators

CRS Clinical Research Services Mannheim GmbH

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Urea Cycle Disorders

Keywords

Urea Cycle Defects, CPSD, OTCD, ASSD, ASLD

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Other

Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

Formation of 13C-urea in plasma

Time Frame

0 - 240 Minutes

Secondary Outcome Measure Information:

Title

Vital signs

Description

blood pressure, heart rate, temperature and respiratory rate at enrollment and after completion

Time Frame

0-240 min

Title

Complete blood count without differential

Time Frame

at enrollement

Title

Adverse events

Time Frame

0-240 mins

Title

Ammonia, Amino acids, Urea in serum

Time Frame

0-240 min

Title

CRP

Time Frame

at enrollment

Title

Venous lactate and blood gases: pH, pCO2, pO2, bicarbonate

Time Frame

at enrollment

Title

Blood glucose

Time Frame

0 - 240 min

Title

pH and bicarbonate

Time Frame

20 and 60 mins after administration

10. Eligibility

Sex

All

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Georg F Hoffmann, Prof Dr med

Organizational Affiliation

Universitätsklinikum Heidelberg Klinik für Kinderheilkunde I

Official's Role

Principal Investigator

Facility Information:

City

CRS Clinical Research Services GmbH (Phase I Unit)

State/Province

Mönchengladbach

ZIP/Postal Code

41061

Country

Germany

Facility Name

Medizinische Hochschule Hannover, Klinik für Kinderheilkunde

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Universitätsklinikum Heidelberg Klinik für Kinderheilkunde I

City

Heidelberg

ZIP/Postal Code

D-69120

Country

Germany

Facility Name

Universitätsklinikum Münster, Zentrum für Kinder- und Jugendmedizin

City

Münster

ZIP/Postal Code

48149

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

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

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