Clinical trial NCT00586807: Metabolic Response to Infliximab in Pediatric Ulcerative Colitis
Official title: Metabolic Response to Infliximab in Pediatric Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Ulcerative Colitis
Protein Metabolism
Energy Expenditure
Keywords: Ulcerative colitis
pediatrics
UC
protein metabolism
energy expenditure
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: ASPEN Rhoads Research Foundation
First posted: 2008-01-04
Enrollment: 10
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The metabolic response to ulcerative colitis, including increased proteolysis and lipolysis and changes in energy expenditure, plays a significant role in the resulting malnutrition from which these patients suffer. Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, has been found to be elevated in children with ulcerative colitis. TNF-alpha has been incriminated in the mechanism of weight loss in many different chronic diseases, and causes net protein and lipid catabolism. Anti-TNF-alpha antibody (infliximab) has been proven to be an effective therapy for ulcerative colitis.

The purpose of this study is to determine changes in protein and lipid metabolism, as well as resting energy expenditure, before and after therapy with anti-TNF-alpha antibody (infliximab) in children with ulcerative colitis. Performing this study will better define the changes in nutrition status observed in these children following remission of active ulcerative colitis, and potentially lead to changes in medical and nutritional management of these children


Eligibility criteria: Inclusion Criteria:

* Male and female children between the ages of six and eighteen years of age
* Endoscopic or histologic evidence of ulcerative colitis
* Active ulcerative colitis determined by primary pediatric gastroenterologist to require anti-tumor necrosis factor-alpha antibody (infliximab) therapy
* Colitis symptom score ≥2
* Screening laboratory tests that meet the following criteria (obtained within 4 weeks of enrollment):

  1. Hemoglobin \>8.0 g/dL
  2. White blood cell count \>3.5 x 109/L
  3. Neutrophils \>1.5 x 109/L
  4. Platelets \>100 x 109/L
  5. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels within 3 times the upper limit of normal.
  6. PPD skin test with skin induration \<5 mm.
  7. Signed written consent from the parent/legal guardian and assent from the child to be obtained prior to enrollment.

Exclusion Criteria:

* Female subjects who are pregnant, nursing, or planning pregnancy.
* Concomitant diagnosis or history of congestive heart failure.
* Serious infection in the 3 months prior to enrollment.
* History of prior or current active or latent tuberculosis.
* Immune deficiency syndrome, including documented human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
* History of systemic lupus erythematosus.
* A transplanted organ.
* Known malignancy or history of malignancy within 5 years of enrollment.
* History of demyelinating disease.
* History of substance abuse.
* History of diabetes mellitus.
* Poor tolerability of venipuncture or lack of venous access during the study period.
* A live virus vaccination within 3 months of enrollment.
* Prior history of infliximab infusion or any other therapeutic agent targeted at reducing tumor necrosis factor-alpha (TNF-alpha).
* Hypersensitivity to any murine proteins or other component of the product.
* Inability to comply with study procedures

Primary outcomes:
measure: Measure protein kinetics and balance in response to anti-TNF-alpha therapy in children with steroid-resistant ulcerative colitis, during both the fasting state and parenteral nutrition infusion.
timeFrame: Week 0 and 2
Secondary outcomes:
measure: 2. Measure energy expenditure by indirect calorimetry in response to anti-TNF-alpha therapy in children with steroid-resistant ulcerative colitis, during both the fasting state and parenteral nutrition infusion.
timeFrame: Week 0 and 2
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University- Riley Hospital for Children
state: Indiana
Study officials:
affiliation: Indiana University
name: Steven J Steiner, MD
role: PRINCIPAL_INVESTIGATOR
References: