· To determine therapeutic efficacy of Tracleer in patients with active Behcet disease. Furthermore:· To study cytokine and immunological patterns and ET-1levels in those patients.
ID
Source
Brief title
Condition
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint
· A decrease in the score in the BDCAF of > 10 in patients with BD with a BDCAF
score of > 20.
Secondary outcome
Secondary endpoints
· ET-1 levels in relation with BDCAF.
· Study of cytokine patterns in relation with therapy and BDCAF.
· T cell patterns in relation with therapy and BDCAF.
Background summary
Behçet*s disease (BD) is a vasculitis characterized by an inflammatory process
of unknown etiology. It originates amongst countries alongside the Silk Route
and is most common in Turkey with a prevalence of 430 per 100.000 in certain
areas. In Western Europe approximately 2 of every 100.000 persons are affected.
Patients present with aphthous oro-genital ulcers, inflammatory skin changes
and uveitis, but may also demonstrate arthritis, thrombosis, neurological
symptoms or colitis. BD can be diagnosed by fulfilling the criteria according
to the International Study Group for BD. The disease specific pathergy test in
which a sterile skin puncture yields a sterile pustule is one of theses
criteria. In this light, BD may worsen after traumatic (skin) events provoking
a Th-1 response in which (pro) inflammatory cytokines interferon-γ (IFN-γ),
tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) are mainly involved2.
The affected sites illustrate vaso-occlusive vasculitis with infiltration of
predominantly activated T-cells and neutrophilic granulocytes. Therefore,
therapy is mainly directed against T-cells, granulocytes or TNF-α. Toxicity and
therapy failure limit the effect of immunosuppressive therapy.
The endothelin-1 (ET-1) receptor antagonist bosentan blocks vaso-occlusion and
inhibits endothelial cell proliferation, inflammation and subsequent fibrosis
in patients with pulmonary hypertension (PHT). This beneficial effect might
also be relevant for patients with BD, because in those patients high levels of
ET-1 have been shown in serum and BAL fluid samples comparable to patients with
PHT. Furthermore, decreased or extremely elevated nitric oxide (NO) levels in
serum and affected tissues in BD patients might reflect a dysfunctional balance
with ET-1 and endothelial stress. These observations might be even more
relevant since endothelial NO synthase (eNOS) polymorphisms have recently been
described BD patients. The more than 100 treated BD patients in the ErasmusMC
outpatient clinic (OPC) constitute the most significant BD population amongst
Dutch Hospitals. It will therefore be very interesting to use the ET-1
inhibitor bosentan to provide new insight in the etiology and a novel treatment
of inflammatory diseases such as BD in this patient cohort.
Study objective
· To determine therapeutic efficacy of Tracleer in patients with active Behcet
disease. Furthermore:
· To study cytokine and immunological patterns and ET-1levels in those
patients.
Study design
Double blinded randomized pilot study
Intervention
Randomization between placebo and Tracleer bid 125mg.
Study burden and risks
No additional risk or burden will be caused by participation with the study.
Tracleer is a registered and safe treatment for various diseases.
Only 4-30cc extra of patient blood will be drawn for investigational purposes
in a group that already provides blood samples during these routine blood
checks.
sGravendijkwal 230
3015 CE ROTTERDAM
NL
sGravendijkwal 230
3015 CE ROTTERDAM
NL
Listed location countries
Age
Inclusion criteria
1. Behcet disease (BD) patients classified according to the criteria according to the International study group for BD
2. BD patients not responding to their usual therapy (BDCAF > 20)
3. Non life -or sight threatening active disease.
3. Adequate birth control measures in women of childbearing age during and for 6 weeks after receiving the last administration.
4. The screening laboratory test results must meet the following criteria:
§ Hemoglobin >= 6.5 mmol/L.
§ WBC >= 3.0 x 109/L.
§ Neutrophils >= 1.5 x 109/L.
§ Platelets >= 100 x 109/L.
§ SGOT (AST), SGPT (ALT) and alkaline phosphatase levels must be within 3 times the upper limit of normal (ULN) range for the laboratory conducting the test.
§ Creatinine clearance > 20 ml/min.
5. Patient must be able to adhere to the study visit schedule and other protocol requirements.
6. The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures.
Exclusion criteria
1. Age < 18 years.
2. Women who are pregnant, nursing, or planning pregnancy within 38 weeks after enrollment.
3. Hypotension, defined as systolic blood pressure less than 85 mm Hg
4. Use of any of the following drugs: glybenclamide, calcineurin inhibitors (eg, cyclosporine A, tacrolimus) or fluconazole. A.
5. Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
6. Liver enzymes > 3 times the ULN, Creatinine clearance of < 20ml/min.
7. Patients with known hypersensitivity to Tracleer® or to drugs with similar chemical structures.
8. Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, infectious or cerebral disease.
9. Malignancy within the past 5 years (except for treated squamous or basal cell carcinoma of the skin without evidence of recurrence).
10. Known recent substance abuse (drugs or alcohol).
11. Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-006714-42-NL |
| CCMO | NL20785.078.07 |