Protein and Energy Metabolism in Pediatric Crohn's Disease

NCT ID: NCT00583232

Last Updated: 2017-03-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2008-12-31

Brief Summary

The metabolic response to Crohn's disease, 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 compare changes in protein and lipid metabolism, as well as resting energy expenditure, before and after therapy with anti-TNF-alpha antibody (infliximab) or corticosteroids in children with recurrent Crohn's disease. Performing this study will better define the changes in nutrition status observed in these children following remission of active Crohn's disease, and potentially lead to changes in medical and nutritional management of these children.

Conditions

Crohn's Disease; Protein Metabolism; Energy Metabolism

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Corticosteroid

Subjects receiving corticosteroid therapy (1-2 mg/kg/day up to 60mg/day) with taper.

Group Type: ACTIVE_COMPARATOR

Stable isotope infusions

Intervention Type: DRUG

Stable isotope infusion will be given via an intravenous catheter. Subjects will receive a priming dose and a continuous dose.

infliximab

Subjects receiving infliximab therapy (5 mg/kg at 0, 2 and 6 weeks, followed by every 8 week therapy)

Group Type: ACTIVE_COMPARATOR

Stable isotope infusions

Intervention Type: DRUG

Stable isotope infusion will be given via an intravenous catheter. Subjects will receive a priming dose and a continuous dose.

Interventions

Stable isotope infusions

Stable isotope infusion will be given via an intravenous catheter. Subjects will receive a priming dose and a continuous dose.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female children between the ages of six and eighteen years of age with recurrence of active Crohn's disease, determined by their primary pediatric gastroenterologist to require either:

1. Corticosteroid therapy ((1-2 mg/kg/d up to maximum of 60 mg/day) with taper, or

2. Infliximab therapy (5 mg/kg at 0, 2, and 6 weeks, followed by q 8 week therapy)

• Crohn's disease of at least 3 months since diagnosis, with gastritis, duodenitis, ileitis, ileocolitis, or colitis, confirmed by endoscopy and biopsy
• PCDAI score >20
• If receiving concomitant medications, must have been on a stable regimen as follows:

1. Subjects on aminosalicylates and/or immunomodulators should be on a stable dose for at least 2 weeks prior to enrollment.

2. Subjects must be off oral, rectal, and parenteral corticosteroids at least 2 weeks prior to enrollment.

• 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.

• For those patients to receive infliximab, PPD skin tests 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

• Local manifestations of Crohn's disease, including fistula(s), strictures, abscesses, or other complications for which surgery may be indicated.
• Surgery for bowel diversion with placement of stoma within 3 months prior to screening.
• Positive stool examination of enteric pathogens including Salmonella and Shigella species, Clostridium difficile, and Giardia lamblia.
• Female subjects who are pregnant, nursing, or planning pregnancy.
• Concomitant diagnosis or history of congestive heart failure.
• Treatment with parenteral nutrition within 4 weeks of enrollment.
• 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.
• 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-a (TNF-a).
• Hypersensitivity to any murine proteins or other component of infliximab for those patients to receive infliximab.
• Inability to comply with study procedures

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Crohn's and Colitis Foundation

OTHER

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven J. Steiner, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana University-Riley Hospital for Children

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

IRB 0506-19

Identifier Type: -

Identifier Source: secondary_id

0506-19

Identifier Type: -

Identifier Source: org_study_id