Intestinal Inflammation in Ankylosing Spondylitis and the Effects of Adalimumab on Mucosal Healing (INTASAH)
Studies with intestinally asymptomatic patients with spondyloarthritis showed that approximately 1/3 had visible ulcers in the colon by scopic examinations and 2/3 had changes detectable by microscopy. Only those patients who improved in arthritis symptoms showed improvement in colonic changes. In these studies only colon and the terminal ileum was examined. Inflammation of the small intestine was not examined. Newer studies have shown an immunological link between Crohns disease and spondyloarthritis but not ulcerative colitis. The investigators wish to examine the small intestine in these patients before and after treatment, since they expect to find ulcers there linking spondyloarthritis to Crohns disease and healing after treatment.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Intestinal Inflammation in Ankylosing Spondylitis Assessed by Fecal Calprotectin, Capsular Endoscopy and Colonoscopy and the Effects of Adalimumab on Mucosal Healing|
- Change Lewis Score Index [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Lewis' score describes the amount of inflammation seen optically by capsular endoscopy.
Gralnek et al. devised and validated the Lewis score index, based on three endoscopic parameters: villous edema, ulcer and stenosis/stricture. Using these parameters, the authors established a score range of 8-4,800 points where: LS < 135 reflects normal mucosal appearances, LS 135-790 mild mucosal inflammatory change and an LS value ≥790 moderate to severe mucosal inflammatory changes.
The patients had endoscopy performed at baseline and again after 20 weeks. The number of patients improving was compared to number of patients deteriorating
- Change in Intestinal Inflammation Measured by Faecal Calprotectin [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Feacal calprotectin is a protein and a marker of the degree of inflammation in the intestine, but not the site of inflammation.
We measured the level calprotectin continuously in each of the patients. Difference was inferred by repeated measurement ANOVA
- Spondyloarthritis Consortium of Canada Score [ Time Frame: one year ] [ Designated as safety issue: No ]Inflammation on MRI assessed by the Spondyloarthritis Consortium of Canada score and a Danish scoring method
- Assessment Group in Ankylosing Spondylitis (ASAS) Core Set for Clinical Practice [ Time Frame: one year ] [ Designated as safety issue: No ]clinical measurements of inflammation in spondyloarthritis patients as described by the Assessment Group in Ankylosing Spondylitis (ASAS)
|Study Start Date:||October 2010|
|Study Completion Date:||March 2014|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Spondylitis patients with active inflammation. Patients are treated with adalimumab
Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given
Other Name: Humira
Patients with inflammatory axial spondyloarthritis according to the assessment group in ankylosing spondylitis (ASAS) criteria (8) and active disease assessed by a physician are recruited in the outpatient clinics of the rheumatology departments, provided that the patient under normal circumstances is expected to benefit from TNF-alpha inhibitor treatment and full fill the criteria for treatment. Screening with a view to participating in the study is carried out in accordance with the inclusion and exclusion criteria. Oral and written patient information about the study, the patient's signing of the informed consent form and the signing of the patient's power of attorney in accordance with the study protocol are also a condition for the inclusion. The including physician will ensure that a potential participant is informed about the right to at least 1 hour's reflection time and the right to have a friend/family member present at the information interview.
If the patient meets the basis for the participation in the study the informed consent form and the power of attorney are signed.
The screened patients are not coded but are identified using their Civil Registration Number (CPR) for several reasons. The study is open-label, which removes the need for blinding of patients as well as investigator. Blood samples are booked electronically and printed labels with CPR number are put on the test tubes for both immediate analysis and storage. This guarantees a more fail-safe method for handling of various analyses, since this procedure is similar to the routine procedure. We find this to be the safest system as the method, by which labels with CPR number follow the patient has been thoroughly tested.
Source data will be kept in the Danish Biologics Online Registry (DANBIO registry) for clinical measures, the electronic patient file for lab data and the paper file for imaging data. Data validity and completeness is controlled by external "good clinical practice" monitoring.
Adalimumab will be supplied as a sterile solution without preservatives for subcutaneous injection in 1 ml prefilled syringes containing adalimumab 40 mg/0.8 ml, to be self-injected by the patient every 2 weeks until week 20. After week 20 patients continue adalimumab treatment 40 mg every other week but may change to injections with pens containing the same drug and dosage. The drug is injected under the skin of the abdomen or the thigh. All patients will be instructed by the study personnel in correct sterile subcutaneous injection of the study drug.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01174186
|Department of Rheumatology U, Aarhus Hospital|
|Aarhus, Denmark, 8000|
|Regional Hospital of Horsens, Department of Medicine|
|Horsens, Denmark, 8700|
|Regional Hospital of Randers, Department of Medicine|
|Regional Hospital of Silkeborg|
|Silkeborg, Denmark, 8600|
|Study Chair:||Henning Glerup, M.D.||Regional Hospital Silkeborg, medical department|
|Study Director:||René D Oestgaard, M.D.||Regional Hospital Silkeborg, medical department|
|Principal Investigator:||Bent Deleuran, M.D.||Department of Medical Microbiology and Immunology Aarhus University|