Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders

Urea Cycle Disorders Clinical Trial

Official title:

Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01541722
• Other study ID #: RDCRN 5109
• Secondary ID: U54HD061221
• Status: Terminated
• Phase: N/A
• First received: February 8, 2012
• Last updated: October 1, 2015
• Start date: February 2012
• Est. completion date: July 2015

Study information

• Verified date: October 2015
• Source: Children's Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: July 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Urea Cycle Disorders
• Urea Cycle Disorders, Inborn

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	The Children's Hospital, Aurora	Aurora	Colorado
United States	Case Western Medical College	Cleveland	Ohio
United States	Baylor College of Medicine	Houston	Texas
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Mount Sinai School of Medicine	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Children's Hospital and Regional Medical Center	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Mark Batshaw	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Rare Diseases Clinical Research Network

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Change from baseline to period of decompensation up to one year	No

External Links

•   Urea Cycle Disorders Consortium