Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders

Status

Terminated

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01541722

Enrollment

Registered

2012-03-01

Start date

2012-02-29

Completion date

2015-07-31

Last updated

2015-10-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Urea Cycle Disorders

Keywords

Urea cycle disorders

Brief 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.

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

Inclusion criteria

* 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)

Exclusion criteria

* 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 * chronic inflammatory diseases * asthma requiring daily long-term control medications * significant respiratory disease.

Design outcomes

Primary

Measure	Time frame	Description
Laboratory values indicating oxidative stress	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.

Countries

Canada, United States

Outcome results