SpondyloarthritisPhase 4INTASAHNCT01174186
Intestinal Inflammation in Ankylosing Spondylitis and the Effects of Adalimumab on Mucosal Healing
A Phase 4 study testing Adalimumab in people with Spondyloarthritis and Enterocolitis, run by Regionshospitalet Silkeborg at 4 sites in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Spondyloarthritis, Enterocolitis
- What is being tested?
- Adalimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesDenmark
- Study dates
- Oct 2010to Mar 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients (18 years and ≤45 years) with axial SpA according to the ASAS criteria
- Active SpA assessed by physician.
- Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.
- Faecal calprotectin ≥ 100mg/kg.
- Negative pregnancy test (serum-HCG) for women of childbearing age before the start of the study. (Women not of childbearing age are defined as postmenopausal for at least 1 year or surgically sterilised (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)). Women of childbearing age included in the study will be required to use contraception during the entire study period (i.e. one of the following: contraceptive pills, intrauterine device, depot injection of gestagen, subdermal implant, hormonal vaginal ring or transdermal patch). In addition, contraception must be used following any discontinuation of the study drug for a period of 150 days.
- Ability and willingness to self-administer the subcutaneous injections or have a person available to administer the injections.
- Ability and willingness to give written informed consent and meet the requirements of the study protocol.
Who cannot join
- Diagnosed inflammatory bowel disease or high risk of intestinal stricture (previous abdominal stricture, radiation of abdomen, major abdominal surgery).
- Non steroid anti inflammatory Drugs (NSAID) ingestion less than 4 weeks before inclusion.
- Psoriasis
- Persons with latent Tuberculosis (TB)(positive Mantoux skin test (>10 mm), positive cultivation for mycobacteria in tissue samples and/or chest X-ray indicating TB) or other risk factors for activation of untreated latent TB.
- Current or recurrent infections or serious infections requiring hospitalisation or treatment with intravenous antibiotics within the last 30 days or oral antibiotics within the last 14 days before inclusion.
- Positive serology for Hepatitis B or C indicating active infection.
Show all 19Show fewer
- Medical history of positive HIV status (in case of suspicion control of HIV test).
- Medical history of histoplasmosis or listeriosis.
- Previous cancer or lymphoid proliferative disease except completely well-treated cutaneous squamous cell carcinoma, basal cell carcinoma or cervical dysplasia.
- Previous diagnosis or signs of demyelinising diseases of the central nervous system (e.g. optic neuritis, disturbance of vision, disturbed gait/ataxia, facial paresis, apraxia).
- Severe renal insufficiency (creatinine clearance < 35 ml/min - normogram).Affected hepatic function: Liver enzymes > 3 x above the normal limit.
- Clinically significant drug or alcohol abuse in the last year or daily current alcohol consumption.
- Diabetes, unstable ischemic heart disease, heart failure (NYHA III-IV), recent apoplexia cerebri (within 3 months), chronic leg ulcer and any other condition (e.g. indwelling catheter) which at the discretion of the investigator means that participation in the protocol would entail a risk for the person in question.
- Anticoagulant treatment.
- Pregnancy or breast-feeding.
- Other clinically significant inflammatory rheumatologic diseases that cannot be related to spondyloarthritis
- Current parvovirus B 19 infection.
- Glucocorticosteroid treatment within the last 4 weeks (except nasal and inhalation steroids).
- Contraindication to study drug.
Trial locations and contacts
4 sites in 1 country.
Denmark4 sites
Department of Rheumatology U, Aarhus Hospital
Aarhus, 8000
Regional Hospital of Horsens, Department of Medicine
Horsens, 8700
Regional Hospital of Randers, Department of Medicine
Randers
Regional Hospital of Silkeborg
Silkeborg, 8600
About this study
Official title: Intestinal Inflammation in Ankylosing Spondylitis Assessed by Fecal Calprotectin, Capsular Endoscopy and Colonoscopy and the Effects of Adalimumab on Mucosal Healing
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.
Read the detailed description
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.
- Conditions
- Spondyloarthritis, Enterocolitis
- Being tested
- Adalimumab
- Medical subject headings
- Spondylarthritis, Enterocolitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdalimumabDrug
Also called Humira
Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given
| Study group | Role | What they receive |
|---|---|---|
| Spondyloarthritis and calprotectin elevated | Active comparator | Spondylitis patients with elevated levels of fecal calprotectin. Patients are treated with adalimumab Receives: Drug: Adalimumab |
| Spondyloarthritis and calprotectin normal | Active comparator | Spondylitis patients with normal levels of fecal calprotectin. Patients are treated with adalimumab. Receives: Drug: Adalimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Baseline to 52 weeks
Secondary outcomes (2)
Spondyloarthritis Consortium of Canada Score
Inflammation on MRI assessed by the Spondyloarthritis Consortium of Canada score and a Danish scoring method
Measured: one year
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)
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2010 (estimated)
- Study startOct 2010
- Primary completionJun 2013
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SpondyloarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regionshospitalet Silkeborg
- Sponsor type
- University, hospital or other
- Collaborators
- Abbott, Medtronic - MITG, Central Denmark Region
- Responsible party
- Principal investigator, Rene Oestgaard, Regionshospitalet Silkeborg
- Investigators
- Henning Glerup, M.D., Study chair, Regional Hospital Silkeborg, medical departmentRené D Oestgaard, M.D., Study director, Regional Hospital Silkeborg, medical departmentBent Deleuran, M.D., Principal investigator, Department of Medical Microbiology and Immunology Aarhus University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01174186
- Sponsor's protocol ID
- 4682724
- Acronym
- INTASAH
- Status last verified
- Nov 2014
- First submitted
- 16 Jul 2010
- Last updated
- 2 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intestinal Inflammation in Ankylosing Spondylitis Assessed by Fecal Calprotectin, Capsular Endoscopy and Colonoscopy and the Effects of Adalimumab on Mucosal Healing
- ClinicalTrials.gov ID
- NCT01174186
- Acronym / sponsor ID
- INTASAH / 4682724
- Conditions
- Spondyloarthritis, Enterocolitis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Regionshospitalet SilkeborgUniversity, hospital or other
- Collaborators
- Abbott, Medtronic - MITG, Central Denmark Region
- Study start
- Oct 2010
- Primary completion
- Jun 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 3 Aug 2010 (estimated)
- Results
- Posted 17 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spondyloarthritis and calprotectin elevated | Active comparator | Drug: AdalimumabSpondylitis patients with elevated levels of fecal calprotectin. Patients are treated with adalimumab |
| Spondyloarthritis and calprotectin normal | Active comparator | Drug: AdalimumabSpondylitis patients with normal levels of fecal calprotectin. Patients are treated with adalimumab. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Patients (18 years and ≤45 years) with axial SpA according to the ASAS criteria
- Active SpA assessed by physician.
- Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.
- Faecal calprotectin ≥ 100mg/kg.
- Negative pregnancy test (serum-HCG) for women of childbearing age before the start of the study. (Women not of childbearing age are defined as postmenopausal for at least 1 year or surgically sterilised (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)). Women of childbearing age included in the study will be required to use contraception during the entire study period (i.e. one of the following: contraceptive pills, intrauterine device, depot injection of gestagen, subdermal implant, hormonal vaginal ring or transdermal patch). In addition, contraception must be used following any discontinuation of the study drug for a period of 150 days.
Key exclusion criteria (19 listed)
- Diagnosed inflammatory bowel disease or high risk of intestinal stricture (previous abdominal stricture, radiation of abdomen, major abdominal surgery).
- Non steroid anti inflammatory Drugs (NSAID) ingestion less than 4 weeks before inclusion.
- Psoriasis
- Persons with latent Tuberculosis (TB)(positive Mantoux skin test (>10 mm), positive cultivation for mycobacteria in tissue samples and/or chest X-ray indicating TB) or other risk factors for activation of untreated latent TB.
- Current or recurrent infections or serious infections requiring hospitalisation or treatment with intravenous antibiotics within the last 30 days or oral antibiotics within the last 14 days before inclusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdalimumabAlso: HumiraTumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given | Drug | Spondyloarthritis and calprotectin elevated, Spondyloarthritis and calprotectin normal |
Primary outcome
Change Lewis Score Index
Time frame: 20 weeks
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: Baseline to 52 weeks
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
2 secondary outcomes
Spondyloarthritis Consortium of Canada Score
Time frame: one year
Assessment Group in Ankylosing Spondylitis (ASAS) Core Set for Clinical Practice
Time frame: one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henning Glerup, M.D. study chair
Regional Hospital Silkeborg, medical department
René D Oestgaard, M.D. study director
Regional Hospital Silkeborg, medical department
Bent Deleuran, M.D. principal investigator
Department of Medical Microbiology and Immunology Aarhus University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Adalimumab in people with Spondyloarthritis and Enterocolitis, run by Regionshospitalet Silkeborg at 4 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change Lewis Score Index (time frame: 20 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2014.