DBPC-Dose-finding-trial of Vitamin D3 for SCIT in Birch Pollen Allergic Patients.
Condition: Hypersensitivity
MeSH terms: Hypersensitivity
Study type: Interventional
Phase: Phase 2

Summary: 
      Low Vitamin D3 (VD3) levels have been reported to be associated with the risk of allergic
      diseases like asthma. VD3 has been demonstrated in vitro, ex vivo and in animal models to
      program the immune system towards anti-inflammatory immune responses. VD3 co-administered
      with allergen may be a promising adjuvant to improve the onset and efficacy of allergen
      immunotherapy (AIT). A clinical trial will be performed to compare the immune effects, the
      tolerability and safety of multiple doses of aVD3 analogue (registered for the intravenous
      route) administered by the subcutaneous (s.c.) route in subjects with allergic rhinitis and
      healthy controls.

      The overall aim is to provide additional (in vivo) support for the use of VD3 as an adjuvant
      in allergen-specific immunotherapy, on top of the existing pre-clinical evidence
      demonstrating that antigen-presenting cells educate the adaptive immune system towards an
      anti-inflammatory response when allergen is seen in the presence of VD3.
    

Detailed description: 
      Low Vitamin D3 (VD3) levels have been reported to be associated with the risk of allergic
      diseases like asthma. In addition, VD3 has been demonstrated in vitro, ex vivo
      (skin-explants) and in animal models to program the immune system towards anti-inflammatory
      immune responses, dominated by regulatory T-cells (Treg) producing Interleukin (IL)-10. In
      response to allergens, healthy individuals by default have such a protective immune response
      against innocuous allergens, whereas allergic subjects develop an inflammatory Th2-type
      response. VD3 co-administered with allergen may be a promising adjuvant to improve the onset
      and efficacy of allergen immunotherapy (AIT), by helping the allergic immune system to divert
      towards an allergen-specific response dominated by regulatory T cells (Treg) and IL-10. A
      clinical trial will be performed to compare the immune effects, the tolerability and safety
      of multiple doses of a VD3 analogue (Zemplar® 5 μg/ml - Abbvie, registered for the
      intravenous route) administered by the subcutaneous (s.c.) route in subjects with allergic
      rhinitis and healthy controls. Primary and secondary outcomes will be compared at baseline
      and at several time points during the study to investigate whether 1) the healthy controls at
      baseline have a more anti-inflammatory systemic cellular immune response to polyclonal
      stimuli and to allergens compared to birch pollen allergic subjects, and 2) whether s.c.VD3
      analogue can skew these responses in allergic subjects towards a profile more resembling the
      one observed in healthy controls. The overall aim is to provide additional (in vivo) support
      for the use of VD3 as an adjuvant in allergen-specific immunotherapy, on top of the existing
      pre-clinical evidence demonstrating that antigen-presenting cells educate the adaptive immune
      system towards an anti-inflammatory response when allergen is seen in the presence of VD3.
    

Intervention name(s): Paricalcitol; Placebo (for paricalcitol)
Intervention type(s): Drug; Drug
Intervention description(s): Vitamin D3 analogue; Injection fluid to mimic paricalcitol injection
Other intervention name(s): Vitamin D3, (Zemplar); fluid to mimic paricalcitol injection
Intervention MeSH terms: Vitamin D; Ergocalciferols
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic