Urea Cycle DisordersNCT01541722
Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders
An observational study of Urea Cycle Disorders, run by Mark Batshaw at 11 sites in 2 countries.
Trial summary
The primary purpose of the proposed study is to characterize the oxidative stress and inflammatory cytokine status in UCD during baseline and decompensated states. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Urea Cycle Disorders
- How many people
- 10 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Feb 2012to Jul 2015
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Urea cycle disorders Inherited metabolic disorders N-acetylglutamate synthase (NAGS) deficiency Carbamyl phosphate synthetase I (CPSI) deficiency Ornithine transcarbamylase (OTC) deficiency Argininosuccinate synthetase (AS) deficiency (Citrullinemia) Argininosuccinate lyase (AL) deficiency (argininosuccinic aciduria Arginase (ARG) deficiency (hyperargininemia) Hyperornithinemia, hyperammonemia and homocitrullinuria (HHH) syndrome, or mitochondrial ornithine carrier (ORNT) deficiency Citrullinemia type II, mitochondrial aspartate/glutamate carrier (CITR) deficiency
Who may be able to join
- Confirmed or highly-likely diagnosis of one of the eight UCDs as established for the Longitudinal Study (5101) (See section 4.2 Inclusion Criteria, Table 4 for diagnostic criteria for patients with UCD)
- Enrolled in Longitudinal Study of Urea Cycle Disorders (RDCRN UCDC #5101)
Who cannot join
- UCD patients who have undergone orthotopic liver transplantation
- Significant chronic medical co-morbidity that might confound the analysis as determined by the site investigators.
- Significant co-morbidities include but are not limited to:
- diabetes, liver failure + cirrhosis
- renal failure
- cardiac disease
Show all 9Show fewer
- chronic inflammatory diseases
- asthma requiring daily long-term control medications
- significant respiratory disease.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
The Children's Hospital, Aurora
Aurora, Colorado, 80045
Case Western Medical College
Cleveland, Ohio, 44106
Baylor College of Medicine
Houston, Texas, 77030
University of California, Los Angeles
Los Angeles, California, 90095
University of Minnesota
Minneapolis, Minnesota, 55455
Mount Sinai School of Medicine
New York, New York, 10029
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University
Portland, Oregon, 97239
Children's Hospital and Regional Medical Center
Seattle, Washington, 98105
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
The primary purpose of the proposed study is to characterize the oxidative stress and inflammatory cytokine status in UCD during baseline and decompensated states.
Read the detailed description
Protein turnover is a cyclic process with a net loss of protein in the fasting state and a net gain in the fed state contributing to nitrogen balance. These physiologic processes are impacted during infection; whole-body protein catabolism exceeds protein synthesis, resulting in net loss of whole-body protein. Patients with urea cycle disorders suffer episodes of periodic hyperammonemic crisis, often in association with intercurrent infections. The immediate cause of this decompensation is the increase in endogenous protein catabolism that is the endpoint of a cascade triggered by intercurrent illness. This increase in protein catabolism leads to elevations of serum amino acids and ammonia production, which cannot be eliminated by a dysfunctional urea cycle.
It is well known that infectious illnesses play a significant role in precipitating metabolic crises in urea cycle defects, presumably by triggering a cascade of events involving the release of inflammatory cytokines that lead to increased protein catabolism. Cytokines have also been implicated as distant mediators of oxidative stress. However, the correlation between oxidative stress, cytokine levels, and severity of a crisis is currently unclear.
The primary purpose of the proposed study is to characterize the oxidative stress and inflammatory cytokine status in UCD during baseline and decompensated states. The investigators will undertake measurements of selected markers of oxidative stress and cytokines in serum and urine during baseline and decompensated states in subjects with UCD in order to establish their prognostic value as biomarkers for disease severity and/or predictors of metabolic decompensation.
- Conditions
- Urea Cycle Disorders
- Keywords
- Urea cycle disorders
- Medical subject headings
- Urea Cycle Disorders, Inborn
What is being measured
The primary outcome is the main question the study is designed to answer.
Laboratory values indicating oxidative stress
Laboratory values that indicate oxidative stress include IL-1, IL-2, IL-6, and IL-8. These values will be analyzed as a panel (not individually) comparing baseline values to values during periods of decompensation.
Measured: Change from baseline to period of decompensation up to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2012 (estimated)
- Study startFeb 2012
- Primary completionJan 2015
- Study completionJul 2015
Why it stopped: DSMB suggested closure due to low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urea Cycle DisordersStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mark Batshaw
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Rare Diseases Clinical Research Network
- Responsible party
- Sponsor-investigator, Mark Batshaw, Children's National Research Institute
- Investigators
- George Diaz, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01541722
- Sponsor's protocol ID
- RDCRN 5109
- Other IDs
- U54HD061221
- Status last verified
- Oct 2015
- First submitted
- 8 Feb 2012
- Last updated
- 2 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders
- ClinicalTrials.gov ID
- NCT01541722
- Acronym / sponsor ID
- RDCRN 5109
- Conditions
- Urea Cycle Disorders
- Keywords
- Urea cycle disorders
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: DSMB suggested closure due to low enrollment
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Mark BatshawUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Rare Diseases Clinical Research Network
- Study start
- Feb 2012
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 1 Mar 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 primary purpose of the proposed study is to characterize the oxidative stress and inflammatory cytokine status in UCD during baseline and decompensated states.
Detailed description
Protein turnover is a cyclic process with a net loss of protein in the fasting state and a net gain in the fed state contributing to nitrogen balance. These physiologic processes are impacted during infection; whole-body protein catabolism exceeds protein synthesis, resulting in net loss of whole-body protein. Patients with urea cycle disorders suffer episodes of periodic hyperammonemic crisis, often in association with intercurrent infections. The immediate cause of this decompensation is the increase in endogenous protein catabolism that is the endpoint of a cascade triggered by intercurrent illness. This increase in protein catabolism leads to elevations of serum amino acids and ammonia production, which cannot be eliminated by a dysfunctional urea cycle.
It is well known that infectious illnesses play a significant role in precipitating metabolic crises in urea cycle defects, presumably by triggering a cascade of events involving the release of inflammatory cytokines that lead to increased protein catabolism. Cytokines have also been implicated as distant mediators of oxidative stress. However, the correlation between oxidative stress, cytokine levels, and severity of a crisis is currently unclear.
The primary purpose of the proposed study is to characterize the oxidative stress and inflammatory cytokine status in UCD during baseline and decompensated states. The investigators will undertake measurements of selected markers of oxidative stress and cytokines in serum and urine during baseline and decompensated states in subjects with UCD in order to establish their prognostic value as biomarkers for disease severity and/or predictors of metabolic decompensation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Urea cycle disorders Inherited metabolic disorders N-acetylglutamate synthase (NAGS) deficiency Carbamyl phosphate synthetase I (CPSI) deficiency Ornithine transcarbamylase (OTC) deficiency Argininosuccinate synthetase (AS) deficiency (Citrullinemia) Argininosuccinate lyase (AL) deficiency (argininosuccinic aciduria Arginase (ARG) deficiency (hyperargininemia) Hyperornithinemia, hyperammonemia and homocitrullinuria (HHH) syndrome, or mitochondrial ornithine carrier (ORNT) deficiency Citrullinemia type II, mitochondrial aspartate/glutamate carrier (CITR) deficiency
Key inclusion criteria (2 listed)
- Confirmed or highly-likely diagnosis of one of the eight UCDs as established for the Longitudinal Study (5101) (See section 4.2 Inclusion Criteria, Table 4 for diagnostic criteria for patients with UCD)
- Enrolled in Longitudinal Study of Urea Cycle Disorders (RDCRN UCDC #5101)
Key exclusion criteria (9 listed)
- UCD patients who have undergone orthotopic liver transplantation
- Significant chronic medical co-morbidity that might confound the analysis as determined by the site investigators.
- Significant co-morbidities include but are not limited to:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Laboratory values indicating oxidative stress
Time frame: Change from baseline to period of decompensation up to one year
Laboratory values that indicate oxidative stress include IL-1, IL-2, IL-6, and IL-8. These values will be analyzed as a panel (not individually) comparing baseline values to values during periods of decompensation.
Results and safety
The study was stopped early (reason given: DSMB suggested closure due to low enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2015.
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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.
George Diaz principal investigator
Icahn School of Medicine at Mount Sinai
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Urea Cycle Disorders, run by Mark Batshaw at 11 sites in 2 countries.
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 2 inclusion and 9 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: stopped early, as of the sponsor's last update on 2 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada. 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 was stopped early (reason given: DSMB suggested closure due to low enrollment). Results are not available in the source record.
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?
Laboratory values indicating oxidative stress (time frame: Change from baseline to period of decompensation up to one year). 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 2 Oct 2015.