CitrullinemiaNOASSDNCT01610089
Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)
A study testing stable isotope infusion in people with Citrullinemia, run by Baylor College of Medicine at 1 site in United States.
Trial summary
The urea cycle consists of a series of chemical reactions through which the body converts toxic waste- nitrogen into a substance called urea that can be disposed of easily. While disposal of nitrogen is the major function of the urea cycle, recent research has shown that some enzymes of the urea cycle are also… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Citrullinemia
- What is being tested?
- stable isotope infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2012to Sep 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants must be adults (18 years and older) with confirmed diagnosis of Argininosuccinate Synthetase Deficiency (ASSD) (Citrullinemia I) who are able to perform study procedures.
- Diagnosis of citrullinemia I must be confirmed by a >10 fold elevation of citrulline in plasma and/or decreased AS enzyme activity in cultured skin fibroblasts or other appropriate tissue and/or identification of pathogenic mutation in the AS gene.
- Subject must be able to take oral or G-tube medication and have a history of adequate compliance of diet and treatment.
- If a woman of child bearing potential and sexually active, participant agrees to use an acceptable method of birth control.
- Most recent serum creatinine level must be less than or equal to 1.5 mg/dl. Serum creatinine measurement may be performed at the subject's local laboratory, but must have been obtained within one year of enrollment.
- Participant agrees to travel to Baylor College of Medicine for the study.
- Control subjects must be over eighteen years of age with no chronic or acute health issues.
Who cannot join
- Pregnancy, current acute illness and current hyperammonemic episode.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: RDCRN 5110, Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)(Version 24Feb12, NIH Approved 4/5/2012)
The urea cycle consists of a series of chemical reactions through which the body converts toxic waste- nitrogen into a substance called urea that can be disposed of easily. While disposal of nitrogen is the major function of the urea cycle, recent research has shown that some enzymes of the urea cycle are also important for the production of nitric oxide. Nitric oxide is an important chemical that has many functions in the human body including regulation of blood pressure. Through this study, the investigators will study the production of nitric oxide in subjects with citrullinemia type 1 by administering stable isotopes to these subjects. Stable isotopes are harmless compounds that can be used to track and measure the production of specific compounds in the human body. The overall goal of this study is to understand if citrullinemia patients have a deficiency of nitric oxide production. This knowledge may have an impact on the treatment of patients with citrullinemia.
Read the detailed description
This is an interventional, case control study to investigate the production of nitric oxide in patients with citrullinemia type I. Through the infusion of isotopes [15N2-ureido] arginine, [5-13C,4, 4, 5, 5-D4] citrulline, [15N]citrulline, 15N sodium nitrate and [15N][18O3] potassium nitrate, the flux of citrulline and nitrate through the urea cycle pathway will be measured in conjunction with an independent measure of total plasma arginine flux. This will be informative in dissecting the contributions of de novo production of arginine vs. exogenous contribution of arginine into total body NO flux. Total body urea production will be measured by the isotopic dilution of constantly infused [18O][13C]urea. These flux measurements will be correlated with the level of residual enzyme activity and clinical phenotype in these citrullinemia patients. The investigators plan to enroll three patients with citrullinemia.
Three unaffected control subjects will also be studied.
- Conditions
- Citrullinemia
- Being tested
- stable isotope infusion
- Keywords
- citrullinemia, argininosuccinate synthetase deficiency, nitric oxide, urea
- Medical subject headings
- Citrullinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stable isotope infusionOther
Also called stable isotopes
Control subjects: [15N2-ureido] arginine (0.69 mg/kg); [5-13C,4,4,5,5-D4] citrulline (0.18mg/kg); 15N citrulline (0.03mg/kg); 15N sodium nitrate (0.003 mg/kg), [15N][18O3] potassium nitrate (0.03 mg/kg) and [18O][13C]urea (1 mg/kg)over 10 minutes. Followed by a 8-hour infusion of [15N2-ureido] arginine (0.69 mg/kg/hr); [5-13C,4,4,5,5-D4] citrulline (0.18mg/kg/hr), [15N][18O3] potassium nitrate (0.003 mg/kg/hr) and [18O][13C]urea (0.1 mg/kg/hr).
Citrullinemia type 1 subjects,[15N2-ureido] arginine (4.14 mg/kg); [5-13C,4,4,5,5-D4] citrulline (1.08 mg/kg); 15N citrulline (0.18mg/kg); 15N sodium nitrate (0.003 mg/kg), [15N][18O3] potassium nitrate (0.03 mg/kg) and [18O][13C]urea (1 mg/kg)over 10 minutes, followed by a 8-hour infusion of [15N2-ureido] arginine (4.14 mg/kg/hr); [5-13C,4,4,5,5-D4] citrulline (1.08 mg/kg/hr), [15N][18O3] potassium nitrate (0.003 mg/kg/hr) and [18O][13C]urea (0.1 mg/kg/hr).
| Study group | Role | What they receive |
|---|---|---|
| stable isotope infusion | Experimental | Infusion of isotopes [15N2-ureido] arginine, [5-13C,4, 4, 5, 5-D4] citrulline, [15N]citrulline, 15N sodium nitrate and [15N][18O3] potassium nitrate,[18O][13C]urea. Receives: Other: stable isotope infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flux of citrulline and nitrate through the urea cycle pathway will be measured in conjunction with an independent measure of total plasma arginine flux.
Endpoint data to be collected include measurement of isotopic enrichments drawn at 0, 6, 7 and 7.5 hours of infusion. Measurements will include urea, carbon-arginine, guanido-arginine, citrulline, nitric oxide, nitrate and 15N-nitrate.
Measured: 0, 6, 7 and 7.5 hours of infusion
Secondary outcomes (1)
Total body urea production will be measured by the isotopic dilution of constantly infused [18O][13C]urea.
Endpoint data to be collected include measurement of isotopic enrichments drawn at 0, 6, 7 and 7.5 hours of infusion. Measurements will include urea, carbon-arginine, guanido-arginine, citrulline, nitric oxide, nitrate and 15N-nitrate.
Measured: 0, 6, 7 and 7.5 hours of infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2012 (estimated)
- Study startDec 2012
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CitrullinemiaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brendan Lee, Baylor College of Medicine
- Investigators
- Brendan Lee, MD, PhD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01610089
- Sponsor's protocol ID
- H-27226
- Acronym
- NOASSD
- Status last verified
- Mar 2015
- First submitted
- 30 May 2012
- Last updated
- 20 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RDCRN 5110, Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)(Version 24Feb12, NIH Approved 4/5/2012)
- ClinicalTrials.gov ID
- NCT01610089
- Acronym / sponsor ID
- NOASSD / H-27226
- Conditions
- Citrullinemia
- Keywords
- citrullinemia, argininosuccinate synthetase deficiency, nitric oxide, urea
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 1 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The urea cycle consists of a series of chemical reactions through which the body converts toxic waste- nitrogen into a substance called urea that can be disposed of easily. While disposal of nitrogen is the major function of the urea cycle, recent research has shown that some enzymes of the urea cycle are also important for the production of nitric oxide. Nitric oxide is an important chemical that has many functions in the human body including regulation of blood pressure. Through this study, the investigators will study the production of nitric oxide in subjects with citrullinemia type 1 by administering stable isotopes to these subjects. Stable isotopes are harmless compounds that can be used to track and measure the production of specific compounds in the human body. The overall goal of this study is to understand if citrullinemia patients have a deficiency of nitric oxide production. This knowledge may have an impact on the treatment of patients with citrullinemia.
Detailed description
This is an interventional, case control study to investigate the production of nitric oxide in patients with citrullinemia type I. Through the infusion of isotopes [15N2-ureido] arginine, [5-13C,4, 4, 5, 5-D4] citrulline, [15N]citrulline, 15N sodium nitrate and [15N][18O3] potassium nitrate, the flux of citrulline and nitrate through the urea cycle pathway will be measured in conjunction with an independent measure of total plasma arginine flux. This will be informative in dissecting the contributions of de novo production of arginine vs. exogenous contribution of arginine into total body NO flux. Total body urea production will be measured by the isotopic dilution of constantly infused [18O][13C]urea. These flux measurements will be correlated with the level of residual enzyme activity and clinical phenotype in these citrullinemia patients. The investigators plan to enroll three patients with citrullinemia.
Three unaffected control subjects will also be studied.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| stable isotope infusion | Experimental | Other: stable isotope infusionInfusion of isotopes [15N2-ureido] arginine, [5-13C,4, 4, 5, 5-D4] citrulline, [15N]citrulline, 15N sodium nitrate and [15N][18O3] potassium nitrate,[18O][13C]urea. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participants must be adults (18 years and older) with confirmed diagnosis of Argininosuccinate Synthetase Deficiency (ASSD) (Citrullinemia I) who are able to perform study procedures.
- Diagnosis of citrullinemia I must be confirmed by a >10 fold elevation of citrulline in plasma and/or decreased AS enzyme activity in cultured skin fibroblasts or other appropriate tissue and/or identification of pathogenic mutation in the AS gene.
- Subject must be able to take oral or G-tube medication and have a history of adequate compliance of diet and treatment.
- If a woman of child bearing potential and sexually active, participant agrees to use an acceptable method of birth control.
- Most recent serum creatinine level must be less than or equal to 1.5 mg/dl. Serum creatinine measurement may be performed at the subject's local laboratory, but must have been obtained within one year of enrollment.
Key exclusion criteria (1 listed)
- Pregnancy, current acute illness and current hyperammonemic episode.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| stable isotope infusionAlso: stable isotopesControl subjects: [15N2-ureido] arginine (0.69 mg/kg); [5-13C,4,4,5,5-D4] citrulline (0.18mg/kg); 15N citrulline (0.03mg/kg); 15N sodium nitrate (0.003 mg/kg), [15N][18O3] potassium nitrate (0.03 mg/kg) and [18O][13C]urea (1 mg/kg)over 10 minutes. Followed by a 8-hour infusion of [15N2-ureido] arginine (0.69 mg/kg/hr); [5-13C,4,4,5,5-D4] citrulline (0.18mg/kg/hr), [15N][18O3] potassium nitrate (0.003 mg/kg/hr) and [18O][13C]urea (0.1 mg/kg/hr). Citrullinemia type 1 subjects,[15N2-ureido] arginine (4.14 mg/kg); [5-13C,4,4,5,5-D4] citrulline (1.08 mg/kg); 15N citrulline (0.18mg/kg); 15N sodium nitrate (0.003 mg/kg), [15N][18O3] potassium nitrate (0.03 mg/kg) and [18O][13C]urea (1 mg/kg)over 10 minutes, followed by a 8-hour infusion of [15N2-ureido] arginine (4.14 mg/kg/hr); [5-13C,4,4,5,5-D4] citrulline (1.08 mg/kg/hr), [15N][18O3] potassium nitrate (0.003 mg/kg/hr) and [18O][13C]urea (0.1 mg/kg/hr). | Other | stable isotope infusion |
Primary outcome
Flux of citrulline and nitrate through the urea cycle pathway will be measured in conjunction with an independent measure of total plasma arginine flux.
Time frame: 0, 6, 7 and 7.5 hours of infusion
Endpoint data to be collected include measurement of isotopic enrichments drawn at 0, 6, 7 and 7.5 hours of infusion. Measurements will include urea, carbon-arginine, guanido-arginine, citrulline, nitric oxide, nitrate and 15N-nitrate.
1 secondary outcome
Total body urea production will be measured by the isotopic dilution of constantly infused [18O][13C]urea.
Time frame: 0, 6, 7 and 7.5 hours of infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2015.
- Baylor College of Medicine WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brendan Lee, MD, PhD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing stable isotope infusion in people with Citrullinemia, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Flux of citrulline and nitrate through the urea cycle pathway will be measured in conjunction with an independent measure of total plasma arginine flux. (time frame: 0, 6, 7 and 7.5 hours of infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2015.