None listed
Conditions
Brief summary
Crohn’s disease is a lifelong condition with symptoms of abdominal pain, diarrhoea, lethargy, vomiting due to an underlying inflammation of the gastrointestinal tract. This is thought to be mediated via elevation of compounds called inflammatory cytokines. There are other health effects not localised to the gut like growth problems and poor bone health (osteoporosis) which may be a consequence of the underlying disease process itself or the use of medication to treat the disease. Often potent steroid medication like Prednisolone are used to control the disease. Whilst this is an effective form of treatment, steroids can have a range of side effects. Growth failure leading to significant short stature, poor bone health with cases of fractures with little or no injury and fracture in the spine have been reported in these groups of children. These of course lead to significant morbidity in the growing years. Statins like atorvastatin have been shown to have a potent effect in lowering cholesterol levels and preventing heart disease from large scale adult studies. Statins have also been used to treat paediatric patients with inherited reason for their high cholesterol. There is some suggestion that statins may have an effect directly at the inflammatory process independent of the level of lowering of cholesterol level. It is thought that statins can lower the level of inflammatory cytokines. As inflammatory cytokine levels are elevated in crohn’s disease and if statins may lower inflammatory cytokine levels, there maybe a role of statins in the treatment of crohn’s disease in children. There are already animal studies and some adult trials that show that statins may help in crohn’s disease and other inflammatory disease like arthritis. In our study, we aim to recruit 60 children with newly diagnosed crohn’s disease (30 in each group) aged between 8-17 years, randomly assigned to either receive atorvastatin or Prednisolone (which is the usual form of treatment in our centre).The study is for a period of 8 weeks. The study aims to show that atorvastatin is no worse than Prednisolone as a medication for induction of remission in reducing actue inflammation in newly diagnosed children with crohn's disease. Patients will attend the study follow-up at baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks after diagnosis. At all of those time points, blood tests will be obtained to assess the inflammatory process, growth factors and bone markers. Faeces will be collected to look at the level of inflammation in the gut. At all those time points, the paediatric crohn’s disease activity index will be obtained and also a quality of life score specific for this population of children. IMPACT-III. At baseline and 8 weeks, an assessment of the child’s state of development (puberty) will also be done. Children will also be asked to self assess their development (puberty) based on validated forms. We hypothesis that statin has an effect on the inflammatory process and will be no worse compared with Prednisolone treatment.
Interventions
Intervention: Oral Atorvastatin (less than 50 kg = 20 mg daily; 50 kg and greater = 40 mg daily) for eight weeks with no dose adjustment.
Sponsors
Royal Children's Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
-Male or females aged 8 to 17 years -Diagnosis of crohn’s diease confirmed on clinical,radiological,endoscopic and/or histological criteria and yet to receive treatment
Exclusion criteria
- Age <8 or > than 17 - Previously treated CD - Newly diagnosed CD but already commenced any form of therapy for induction of remission including any form of steroid therapy. - Any underlying chromosomal disorders eg Down’s syndrome, Turner’s syndrome -Any underlying autoimmune diagnosis eg juvenile arthritis, connective tissue disease, coeliac disease, type 1 diabetes mellitus, addison’s disease, hypothyroidism, hyperthyroidism, polyglandular endocrinopathy. - Primary bone disorder eg osteogenesis imperfecta - A secondary chronic medical diagnosis that may have an impact on linear growth and bone health - Previous adverse reaction to statins - Current pregnancy or sexually active and not using a medically acceptable form of birth control. (All girls who are menarchal or > 14 years of age will need to undego a pregnancy test before being eligible for the study). - History of clinically significant organic or psychiatric disease or findings on physical examination, which in the opinion of the Investigator would prevent the patient from completing the study. - Ongoing use of oral corticosteroid for a different medical condition prior to diagnosis - Ongoing use of immunomodulators eg azathioprine, methotrexate; biologics eg anti TNF therapy for a different medical condition (to exclude patients with another known chronic inflammatory condition) - Ongoing use of growth hormone, sex steroid, thyroxine and/or steroid replacement (hydrocortisone, prednisolone, dexamathasone) for an underlying endocrine diagnosis (to exclude conditions like growth hormone deficiency, hypopituitarism) - Ongoing use of cyclosporine, fibrates, CYP3A4 inhibitors, itraconazole, HIV protease inhibitors (concurrent medication absolutely contraindicated with atovarstatin). - AST or ALT > 2 x upper limit of normal from investigations performed in the last 4 weeks.
Outcome results
None listed