Protein and Energy Metabolism in Pediatric Crohn's Disease

NCT00583232 | Completed Phase 1 DMC

• 2 other identifiers: 0506-19IRB 0506-19
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Keywords

Pediatric; Crohn's disease; protein metabolism; energy metabolism

Outcome Measures

Primary Outcomes (1)

• Compare whole body and splanchnic protein kinetics and balance in response to corticosteroid and anti-TNF-alpha therapies in the fasting state and during enteral nutrition infusion.

  Week 0, 2 and 14

Secondary Outcomes (7)

• Compare the effects of corticosteroid and anti-TNF-alpha therapies on resting and total energy expenditure.

  Week 0, 2 and 14

• Compare the effects of corticosteroid and anti-TNF-alpha therapies on free fatty acid metabolism

  Week 0, 2 and 14

• Compare the effects of corticosteroid and anti-TNF-alpha therapies on quality of life

  Week 0, 2, and 14

• Comparing the effects of corticosteroid and anti-TNF-alpha therapies on bone turnover and bone density

  Week 0,2 and 14

• Compare the effects of corticosteroid and anti-TNF-alpha therapies on body composition.

  Week 0, 2 and 14

Study Arms (2)

Corticosteroid

ACTIVE COMPARATOR

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

Drug: Stable isotope infusions

infliximab

ACTIVE COMPARATOR

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

Drug: Stable isotope infusions

Interventions

Stable isotope infusions DRUG

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

Corticosteroid; infliximab

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• Corticosteroid therapy ((1-2 mg/kg/d up to maximum of 60 mg/day) with taper, or
• 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:
• Subjects on aminosalicylates and/or immunomodulators should be on a stable dose for at least 2 weeks prior to enrollment.
• 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):
• 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.
• For those patients to receive infliximab, PPD skin tests with skin induration \<5 mm.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indiana University: lead
• GlaxoSmithKline: collaborator
• Crohn's and Colitis Foundation: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Indiana University-Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Steven J. Steiner, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 31, 2007
• Study Start: February 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: March 16, 2017

Record last verified: 2017-03

Locations

US (1)