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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


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
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