subcutaneous immunotherapy in allergic rhinitis (AR) patients with allergies to birchpollen
Conditions
Sponsors
Academisch medisch centrum Amsterdam
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent 2. Age =18 = 65 years 3. Moderate to severe birch-pollen-induced AR/ARC of at least 2 years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (Appendix 1, see manual) with or without concomitant mild to moderate persistent asthma 4. FEV1>70% for patients with a history of asthma, FEV1>70% or PEF>80% for patients without a history of asthma 5. A positive SPT (mean wheal diameter = 3mm compared to negative control and negative control should be negative) for birch pollen assessed within 1 year before randomization 6. A positive ImmunoCAP (>0.7 kU/L) for birch pollen 7. A positive tNPT (for rules when a tNPT is positive see ref 40a) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Clinically relevant co-sensitization (others than hazel, alder and elm) expected during the birch-pollen season. 2. Chronic asthma with an FEV1<70 % of predicted value. 3. History of AIT (SCIT or SLIT) with any allergen within the past 5 years 4. Ongoing AIT (SCIT or SLIT) with any allergen(s) during the study period 5. Current Treatment with VD3 analogue. 6. Vaccination within one week before or during the treatment phase. 7. Immunosuppressive or biological medication (e.g. IL-5, anti-IgE therapy) within the last six months prior to inclusion and up to end of trial (EoT). 8. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs. 9. Uncontrolled asthma or other active respiratory diseases. 10. Active malignancies or any malignant disease during the previous 5 years. 11. Severe uncontrolled diseases that could increase the risk for patients participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or haematological disorders. 12. Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study. 13. Moderate to severe nasal obstructive diseases that preclude a TNPT (e.g., septal deviation, nasal polyps) or nasal/sinus surgery in the last 3 months. 14. Diseases with a contraindication for the use of adrenaline (e.g. hyperthyroidism, glaucoma). 15. Use of systemic steroids within 4 weeks before start of the study and during the study. 16. Treatment with systemic and local ß-blockers. 17. Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or oral contraceptive pill). 18. Alcohol, drug or medication abuse within the past year. 19. Any clinically significant abnormal laboratory parameter at screening. 20. Lack of cooperation or compliance. 21. Any physical or mental condition that precludes administration of SCIT, compliance or participation in a clinical trial. 22. Patients who are students or employees of the institution or 1st grade relatives or partners of the investigators 23. Participation in a clinical trial within 3 months prior to the current trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is the assessment of serological and cellular immunological changes and kinetics thereof induced by SCIT with VD3 compared to SCIT alone in patients with moderate to severe allergic rhinitis/rhino-conjunctivitis caused by birch pollen in a pre-seasonal short-term course of SCIT. To this end, the primary outcome of the study is the IL-10 production by PBMCs in response to allergen-specific stimulation after 5 weeks of treatment with VD3 analogue Zemplar® compared to placebo (visit 7). ;Secondary Objective: Differences in the following parameters will be measured after (5 and) 11 weeks of treatment with SCIT +/- VD3: • The IL-10 production by PBMCs in response to allergen-specific or polyclonal stimulation. • Cellular composition of PBMC (Th1,2,17,22, Tregs, B cells, and APCs. • PBMC proliferatiskinon and cytokine production in response to allergen or polyclonal stimuli. • Intracellular cytokines in response to PMA/ionomycin. • IgE, IgG and IgG4 responses in serum to birchpollen and Bet v 1. • The functional blocking antibody capacity of IgG/IgG4. • Titrated SPT with birchpollen extract as a surrogate clinical marker of efficacy. • Monitoring of epigenetic changes. • Identification of predictive and efficacy-associated biomarkers by transcriptomics on nasal brushing. • Clinical efficacy by titrated nasal provocation test, peak nasal inspiratory flow, the combined symptom medication score (CSMS) and an electronic diary (e-diary). ;Primary end point(s): The primary outcome of the study is the IL-10 production by PBMCs in response to allergen-specific stimulation after 5 weeks of treatment with VD3 analogue Zemplar® compared to placebo. ;Timepoint(s) of evaluation of this end point: 5 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The IL-10 production by PBMCs in response to allergen-specific stimulation after 11 weeks of treatment with VD3 analogue Zemplar® compared to placebo. • The IL-10 production by PBMCs in response to polyclonal stimulation after 5 and 11 weeks of treatment with VD3 analogue Zemplar® compared to placebo. • Determination of the difference between cellular composition of PBMC with respect to Th1, Th2, Th17, Th22, and Treg cells, B cells, and antigen-presenting cells (APC) induced by SCIT with VD3 compared to SCIT alone in patients with moderate to severe allergic rhinitis/rhino-conjunctivitis caused by birch pollen after 5 and 11 weeks of treatment. • Determination of the difference between PBMC proliferation and cytokine production in response to allergen (Bet v 1) induced by SCIT with VD3 compared to SCIT alone in patients with moderate to severe allergic rhinitis/rhino-conjunctivitis caused by birch pollen after 5 and 11 weeks of treatment. • Determination of the difference between PBMC proliferation and cytokine production in response to polyclonal stimuli (aCD3/aCD28) induced by SCIT with VD3 compared to SCIT alone in patients with moderate to severe allergic rhinitis/rhino-conjunctivitis caused by birch pollen after 5 and 11 weeks of treatment. • Determination of the difference between intracellular cytokine measurements in response to PMA/ionomycin induced by SCIT with VD3 compared to SCIT alone in patients with moderate to severe allergic rhinitis/rhino-conjunctivitis caused by birch pollen after 5 and 11 weeks of treatment. • Determination of the changes in IgE, IgG and IgG4 antibody responses in serum to birch pollen and Bet v 1 induced by SCIT with VD3 compared to SCIT alone in patients with moderate to severe allergic rhinitis/rhino-conjunctivitis caused by birch pollen after 5 and 11 weeks of treatment. • Determination of changes in a so-called IgE facilitated allergen-binding assay (FAB) and in a rat basophilic leukemia cell (RB | — |
Countries
Netherlands
Contacts
Public ContactClinical trial Information
Academisch medisch centrum Amsterdam
Outcome results
None listed