New Immunomodulatory Therapy Strategies in Chronic Reactive Arthritis
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00244179|
Recruitment Status : Unknown
Verified September 2006 by Charite University, Berlin, Germany.
Recruitment status was: Recruiting
First Posted : October 26, 2005
Last Update Posted : September 8, 2006
|First Submitted Date ICMJE||October 24, 2005|
|First Posted Date ICMJE||October 26, 2005|
|Last Update Posted Date||September 8, 2006|
|Study Start Date ICMJE||January 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00244179 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||New Immunomodulatory Therapy Strategies in Chronic Reactive Arthritis|
|Official Title ICMJE||New Immunomodulatory Therapy Strategies in Chronic Reactive Arthritis: Immunostimulation Plus Antibiotic Versus Immunosuppression Plus Antibiotic Versus Conventional Standardtherapy|
Studybackground Enteric reactive arthritis (ReA) is an extraintestinal manifestation of an infection of colon mucosa caused by enterobacteria. At least in the chronic courses of ReA a bacterial persistence can be assumed which is most likely to be located in colon mucosa or colon associated lymph nodes. The persistence of bacteria might be in consequence of an insufficient t-helper-immune-response.
On the other hand the persistence of the pathogen itself could be harmless and the local immune-pathology could be caused by a hypersensitivity immune response The project in hand shall assess whether 1.) immune stimulation or immune suppression is the best therapy for chronic reactive arthritis and 2.) enteric reactive arthritis is based on bacterial persistence or a hypersensitivity immune response.
By gaining these data we hope to be able to draw conclusions concerning the pathogenesis and therapies of other infections that affect the mucosa.
ReA occurs after infection of the intestine (enteric ReA) or after urogenital infection caused by chlamydia (urogenital ReA). Both forms of ReA are pathogenetically und immunogenically closely related and are treated as one entity.
Patients who are enrolled in the trial with enteric ReA (colon as possible location of bacterial persistence), not those with urogenital ReA (location of bacterial persistence not known) undergo colonoscopy before and after treatment-period to obtain colon biopsies for further work up.
Patients with knee involvement (arthritis of knee) undergo arthroscopy before and after treatment-period to obtain synovial biopsies for further work up.
Recently collected data form our group concerning patients with ankylosing spondylitis under therapy with infliximab or etanercept have shown that the potential of CD4- and CD8-positive t-cells to produce interferon gamma (IFN Gamma) or tumornecrosisfactor alpha (TNF-Alpha) after antigen-specific or –unspecific stimulation was distinct reduced under therapy with infliximab, whereas this potential under therapy with etanercept increased.
In context with recently collected data concerning Crohn´s disease it can be assumed that by binding not only soluble TNF-Alpha but as well membrane-associated TNF-Alpha infliximab induces apoptosis of t-cells, whereas etanercept induces no apoptosis. These results could explain, why infliximab but not etanercept is effective in treating Crohn´s disease Furthermore the induction of apoptosis could explain why therapy with infliximab is associated with a higher incidence of tuberculosis compared to etanercept.
By means of FACS (Fluorescence activated cell sorting) we want to examine, whether TNF-blocking agents in patients with chronic ReA induce a t-cell-suppression and compare the cytokine-pattern of CD4- and CD8-positive t-cells from patients treated with infliximab with the cytokine-pattern of CD4- and CD8-positive t-cells from patients treated with etanercept.
The comparison of both therapies - infliximab and etanercept – is of special interest, because both TNF-blocking agents obviously have a different active profile as well as different side effects.
Background for dosage Ciprofloxacin 2 x 500 mg p.o. daily is conventional therapy for treating infections with enterobacteria.
Clinical trials with infliximab 5 mg/kg in patients suffering from ankylosing spondylitis have been successfully performed. Dosages of infliximab 1 – 10 mg/kg have been used in treating succesfully patients with rheumatoid arthritis. A dosage of 5 mg/kg was more effective than 1 mg/kg, but 10 mg/kg was only slightly better. Infliximab has been approved for the indication rheumatoid arthritis and ankylosing spondylitis.
Clinical trials with etanercept 25 mg s.c. 2 x per week in patients suffering from ankylosing spondylitis and rheumatoid arthritis have been performed successfully and effectively. Etanercept has been approved for the indication ankylosing spondylitis, rheumatoid arthritis and psoriasic-arthritis.
To treat patients suffering from tuberculosis who do not respond to conventional anti-tuberculosis-therapy IFN-g (interferon-gamma) 3 x 100 – 150 µg/week s.c. has been succesfully administered.
In a clinical trial to assess the efficacy in rheumatoid arthritis IFN-g 50 µg was administered daily during the first three weeks and every other day in the last week.
Patients who receive standard-therapy (Sulphasalazine, Methotrexate, Leflunomide) are treated with common dosages of these drugs that are deduced from the common treatment of rheumatoid arthritis.
Background for selection of patients 80% of patients suffering from acute ReA heal up within 6 months. About 40% of patients have severe symptoms for more than 6 months and about 20% develop a chronic course of arthritis.
These patients with chronic ReA are regrettably insufficiently treated with the available drugs (NSAID, Methotrexate, Sulphasalazine, Leflunomide).
Patients who are enrolled in this trial have to have a definite chronic ReA (disease duration of at least 12 months), a joint pain of > 4 (visual analogue scale, 0-10), a constant demand of NSAID and an active arthritis affecting at least one joint.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Educational/Counseling/Training
|Condition ICMJE||Reactive Arthritis|
|Study Arms||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 70 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Germany|
|Removed Location Countries|
|NCT Number ICMJE||NCT00244179|
|Other Study ID Numbers ICMJE||ReA01|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Charite University, Berlin, Germany|
|PRS Account||Charite University, Berlin, Germany|
|Verification Date||September 2006|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP