Adverse Effects of Glucocorticoid Therapy on Bone in Childhood Crohn's Disease

This study will compare two current first-line treatments for childhood Crohn's Disease, steroids versus a liquid diet, and determine the effects of these treatments on bone health, quality of life and treatment efficacy.

Study Overview

• Status: Unknown
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: prednisolone; Dietary supplement: Alicalm (polymeric liquid formula)

Detailed Description

Crohn's Disease is a very serious inflammatory gut disorder that often first presents in childhood. Once present, the underlying condition remains for life. It usually responds well to medical treatment which brings about a disease 'remission' but is inclined to become active again at intervals (relapses). When it is active, children are very unwell with reduced energy, loss of appetite and distressing abdominal symptoms (pain, diarrhea, etc.). Active disease can be treated in two very different ways - either with a 3-month course of steroids (tablets), or with a 6-week course of so called "liquid diet therapy (LDT)." With LDT, children receive all of their nutrition in liquid form. Both treatments have advantages and disadvantages. Both are quite effective, often controlling symptoms within days. Steroids may cause various side effects including thinning of bones (osteoporosis) with increased risk of fractures. LDT is somewhat challenging because normal (solid) foods are not allowed during the period of treatment. Both steroids and LDT are widely used - steroids predominately in the USA and LDT elsewhere. There is controversy as to which is best. This study aims to determine which should be preferred.

In this clinical study, children presenting with Crohn's disease will be randomly assigned to either steroid treatment or LDT and followed up for a period of one year. During that time the assigned treatment will be used for any episodes of active disease. We will study a total of 80 children attending the Paediatric Gastroenterology Units in Birmingham, Bristol, Liverpool, Oxford, Sheffield and St. George's Hospital in London. Various outcomes will be compared in the two groups. We will examine the recovery rates (success in bringing about remission) and the frequency of subsequent relapses. We will compare growth and physical development, because active Crohn's disease and possibly steroids may have adverse effects on these processes. A special focus of the study will be on the effect of the disease and its treatment on bone health. Using special blood and urine tests and bone scans we will compare bone growth and density in the two groups. Finally, it is crucially important that we consider the impact of the disease and its treatment on the young person on the basis of their own individual perspective. To do this we will compare the 'quality of life' of children in the two treatment groups, using a questionnaire specially designed to measure this aspect in young people with Crohn's disease.

This study will thus enable us to undertake a comprehensive comparison of the two major first-line treatments used in childhood Crohn's Disease. This is crucially important, and no such study has previously been undertaken

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom, BS2 8BJ
    • Recruiting
    • Bristol Royal Hospital for Sick Children
    • Principal Investigator: Christine Spray
  • London, United Kingdom, SW17 0QT
    • Recruiting
    • St George'S University Hospital
    • Principal Investigator: Sally Mitton
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L12 2AP
      • Recruiting
      • Royal Liverpool Children's Hospital
      • Principal Investigator: Mark Dalzell
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DZ
      • Recruiting
      • Oxford Children's Hospital
      • Principal Investigator: Astor Rodrigues
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2TH
      • Recruiting
      • Sheffield Children's Hospital
      • Principal Investigator: Christopher Taylor
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B4 6NH
      • Recruiting
      • Birmingham Children's Hospital
      • Contact: Kelly Spencer; Phone Number: +44 (0)121 333 9542; Email: k.spencer@bham.ac.uk
      • Principal Investigator: M Stephen Murphy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Active Crohn's Disease with PCDAI > 20
• Aged 7 - 17 with possibility of 1 year follow-up

Exclusion Criteria:

• Previous treatment for Crohn's Disease with liquid diet or glucocorticoid therapy
• Isolated orofacial granulomatosis
• Intravenous glucocorticoid therapy immediately indicated
• Planned surgical intervention for CD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2	Dietary supplement: Alicalm (polymeric liquid formula); Subjects will receive all of their nutritional requirements in the form of a nutritionally balanced polymeric feed, volume based on EAR for age. Duration of 5 to 8 weeks with subjects returning to a "normal" unrestricted diet by 10 weeks.; Other Names: Alicalm (SHS International Ltd.)
Active Comparator: 1	Drug: prednisolone; Standard treatment regimens based on body weight will be used (approximately 2 mg per kg), with a stepwise dose reduction over a 10-14 week period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bone mineral density change based on DXA measurement at 1 year	12 months post-recruitment

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse effects	12 months
Proportion in remission	6 weeks
Change in PCDAI, HAB and pHBS	6 weeks
Quality of life throughout treatment period, using IMPACT III measurements	12 months
Baseline urine 11B-HSD1 and bone formation	6 weeks
Baseline urine 11B-HSD1 activity and change in bone mineral density	12 months
Change in urine 11B-HSD1 activity and PCDAI in patients before and after treatment with LDT and CST	12 months
Growth impairment	12 months
Adherence to randomised therapy for relapses	12 months

Collaborators and Investigators

• Sponsor: University Hospital Birmingham
• Collaborators: SHS International; Children's Memorial Research Foundation; St George's University Hospital Research Foundation
• Investigators: Study Director: M. Stephen Murphy, University of Birmingham

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Anticipated): January 1, 2010
• Study Completion (Anticipated): January 1, 2010

Study Registration Dates

• First Submitted: January 24, 2008
• First Submitted That Met QC Criteria: January 24, 2008
• First Posted (Estimate): February 7, 2008

Study Record Updates

• Last Update Posted (Estimate): December 30, 2008
• Last Update Submitted That Met QC Criteria: December 29, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Quality of Life; Children; Crohn Disease; Prednisolone; Bone Density; Liquid Diet Therapy; Metabolic Bone Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone
• Other Study ID Numbers: RG_06_266; EudraCT: 2006-000209-48; CTA: 21761/0213/001