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| Name | Class |
|---|---|
| Abbott | INDUSTRY |
| Medtronic - MITG | INDUSTRY |
| Central Denmark Region | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Spondyloarthritis and calprotectin elevated | Active Comparator | Spondylitis patients with elevated levels of fecal calprotectin. Patients are treated with adalimumab |
|
| Spondyloarthritis and calprotectin normal | Active Comparator | Spondylitis patients with normal levels of fecal calprotectin. Patients are treated with adalimumab. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adalimumab | Drug | Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change Lewis Score Index | 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 | 20 weeks |
| Change in Intestinal Inflammation Measured by Faecal Calprotectin | 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 | Baseline to 52 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Spondyloarthritis Consortium of Canada Score | Inflammation on MRI assessed by the Spondyloarthritis Consortium of Canada score and a Danish scoring method | one year |
| Assessment Group in Ankylosing Spondylitis (ASAS) Core Set for Clinical Practice |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Henning Glerup, M.D. | Regional Hospital Silkeborg, medical department | Study Chair |
| René D Oestgaard, M.D. | Regional Hospital Silkeborg, medical department | Study Director |
| Bent Deleuran, M.D. | Department of Medical Microbiology and Immunology Aarhus University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Rheumatology U, Aarhus Hospital | Aarhus | 8000 | Denmark | |||
| Regional Hospital of Horsens, Department of Medicine |
Patient on current non-steroidal anti-inflammatory (NSAID) treatment were subjected to a 4 week long wash-out period, because NSAID can cause falsely elevated fecal calprotectin levels
SpA patients eligible for anti-TNF treatment as described by ASAS guidelines were included from outpatient clinics in Northern Jutland, Denmark. Patients were included over a 2 years and three months time span
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| ID | Title | Description |
|---|---|---|
| FG000 | Calprotetin Elevated | Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given |
| FG001 | Calprotectin Normal | Spondylitis patients with active inflammation and normal calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
n=15 in each group was determined by power calculations from previous pilot trials on differences in calprotectin
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| ID | Title | Description |
|---|---|---|
| BG000 | Calprotetin Elevated | Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given |
| BG001 | Calprotectin Normal |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change Lewis Score Index | 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 | Because endoscopy has a small risk for perforation. The study was designed so only patients with active inflammation at baseline had follow-up endoscopy performed. Because all patients with normal calprotectin levels had normal endoscopy, follow-up was only performed on this group of patients. | Posted | Median | Inter-Quartile Range | units on a scale | 20 weeks |
|
Adverse events were collected during the entire follow-up period of one year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Calprotetin Elevated | Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment | Patient admitted with abdominal pains after consuming alcohol. Was discharged the next day after lab results came out normal and abdominal pains had subsided |
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15 participants in each group is not many, but the number was selected based on an a priori analysis.
NSAID wash-out period of 4 weeks was chosen as best estimate. Loading dose of adalimumab was given to calprotectin elevated group
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| René Oestgaard | Silkeborg Regional Hospital | 0045 78 41 50 00 | ostgard@immunology.au.dk |
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| ID | Term |
|---|---|
| D025241 | Spondylarthritis |
| D004760 | Enterocolitis |
| ID | Term |
|---|---|
| D013166 | Spondylitis |
| D013122 | Spinal Diseases |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D000068879 | Adalimumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
clinical measurements of inflammation in spondyloarthritis patients as described by the Assessment Group in Ankylosing Spondylitis (ASAS)
| one year |
| Horsens |
| 8700 |
| Denmark |
| Regional Hospital of Randers, Department of Medicine | Randers | Denmark |
| Regional Hospital of Silkeborg | Silkeborg | 8600 | Denmark |
Spondylitis patients with active inflammation and normal calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Bath Ankylosing Spondylitis Disease Activity Index >4 | Patient answered composite index for describing disease activity. Range from 0-10. Higher scores indicate higher disease activity | Number | participants |
|
| No effect of NSAID | Number | participants |
|
| Expert opinion of active disease | Number | participants |
|
| Calprotetin Elevated |
Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given |
|
|
| Primary | Change in Intestinal Inflammation Measured by Faecal Calprotectin | 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 | 15 patients in each group was included. 3 in the calprotectin negative group patients did not fulfill the entire study period (1 lost to follow-up, 2 withdrew consent). Data analysed as last observation carried forward. | Posted | Median | Inter-Quartile Range | mg/g | Baseline to 52 weeks |
|
|
|
| Secondary | Spondyloarthritis Consortium of Canada Score | Inflammation on MRI assessed by the Spondyloarthritis Consortium of Canada score and a Danish scoring method | Not Posted | one year |
| Secondary | Assessment Group in Ankylosing Spondylitis (ASAS) Core Set for Clinical Practice | clinical measurements of inflammation in spondyloarthritis patients as described by the Assessment Group in Ankylosing Spondylitis (ASAS) | Not Posted | one year |
| 2 |
| 15 |
| 0 |
| 15 |
| EG001 | Calprotectin Normal | Spondylitis patients with active inflammation and normal calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week | 0 | 15 | 0 | 15 |
|
| Gastro intestinal bleeding | Gastrointestinal disorders | Systematic Assessment | Admitted to hospital because of severe anemia. Patient was bleeding from a Meckel's diverticulum |
|
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| D001168 |
| Arthritis |
| D007592 | Joint Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |