Metabolic Response to Infliximab in Pediatric Ulcerative Colitis

Sponsor

Indiana University (Other)

Overall Status

Terminated

CT.gov ID

NCT00586807

Collaborator

ASPEN Rhoads Research Foundation (Industry)

Enrollment

Location

Arm

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis Protein Metabolism Energy Expenditure	Other: Stable amino acid isotopes	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Metabolic Response to Infliximab in Pediatric Ulcerative Colitis

Study Start Date :

Jun 1, 2005

Actual Primary Completion Date :

Sep 1, 2008

Actual Study Completion Date :

Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Other: Infliximab Subjects on infliximab	Other: Stable amino acid isotopes Stable amino acid isotopes given per IV, dose based on weight and given over the length of the study visit.

Arm

Intervention/Treatment

Other: Infliximab

Subjects on infliximab

Other: Stable amino acid isotopes

Stable amino acid isotopes given per IV, dose based on weight and given over the length of the study visit.

Outcome Measures

Primary Outcome Measures

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. [Week 0 and 2]

Secondary Outcome Measures

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. [Week 0 and 2]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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):

Hemoglobin >8.0 g/dL
White blood cell count >3.5 x 109/L
Neutrophils >1.5 x 109/L
Platelets >100 x 109/L
Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels within 3 times the upper limit of normal.
PPD skin test with skin induration <5 mm.
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