HypersensitivityPhase 2BM4SITNCT02686827

DBPC-Dose-finding-trial of Vitamin D3 for SCIT in Birch Pollen Allergic Patients.

A Phase 2 study testing Paricalcitol in people with Hypersensitivity, run by Laurian Jongejan at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Hypersensitivity
What is being tested?: Paricalcitol
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 44 participants
Where: 1 siteNetherlands
Study dates: Oct 2015to Oct 2016
Phase: Phase 2
Are there results?: None posted in the registry

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 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Signed informed consent
Age ≥18 ≤ 60 years
Allergic rhinitis/rhino-conjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma based on relative symptoms and allergy tests.
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 OR a positive serum specific anti-birch IgE-test (>0.7 U/ml)
Signed informed consent
Age, gender and location matched to a study subject. An age matched control is defined as the age of the study subject ±5 years.
No history of respiratory allergies and no nasal symptoms at screening.
A negative SPT (a positive outcome is defined as a mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative) assessed within 1 year before randomization OR a negative serum specific IgE test for aeroallergens.

Who cannot join

A history of allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) within the 5 years before inclusion/screening visit.
Treatment with parenteral Vitamin D3 analogue in the year before inclusion
Significant, ongoing nasal symptoms caused by other allergens at study onset
A history of Hypercalcemia, Hypophosphatemia or vitamin D toxicity
Any vaccination within one week before randomization
Treatment with experimental products within the last 3 months or during the study or biologicals (including anti-IgE or TNF- α treatment) within the last 6 months or during the study

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Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
Uncontrolled asthma or other active respiratory diseases
Malignancies or any malignant disease during the previous 5 years
Severe uncontrolled diseases that could increase the risk for subjects 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 hematological disorders
Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study
Use of preparations containing calcium or magnesium such as thiazide, diuretics, antacides.
Use of systemic steroids within 4 weeks before screening and during the study
Daily use of ketoconazole cream or immunosuppressive creams at planned injection site less than 7 days before or during the study
Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or -pill)
Any clinically significant abnormal laboratory parameter at screening
Any physical or mental condition that precludes compliance or participation in a clinical trial
Subjects who are employees or students of the institution or 1st grade relatives or partners of the investigators

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

Academic medical center
Amsterdam, 1100 AZ

Other trials in Netherlands

About this study

Official title: A Randomized, Double-blind, Placebo-controlled Study to Determine the Immune Effects of Multiple Doses of Vitamin D3 in Patients With Allergic Rhinitis/Rhino-conjunctivitis Caused by Birch Pollen and in Healthy Control Subjects.

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.

Read the 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.

Conditions: Hypersensitivity
Being tested: Paricalcitol, Placebo (for paricalcitol)
Medical subject headings: Hypersensitivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ParicalcitolDrug
Also called Vitamin D3, (Zemplar)
Vitamin D3 analogue
Placebo (for paricalcitol)Drug
Also called fluid to mimic paricalcitol injection
Injection fluid to mimic paricalcitol injection

Study groups in NCT02686827
Study group	Role	What they receive
Paricalcitol (Vitamin D3)	Experimental	paricalcitol, (Zemplar® 5 μg/ml Abbvie), will be administered via the subcutaneous route 4 times at 0.5 ml (registered dose of 5 μg/ml, thus 2.5 μg per sub-cutaneous injection). The minimum time interval between two injections is 4 days, which is a significantly lower frequency than the prescribed maximum of 3 times a week or every other day. Receives: Drug: Paricalcitol
Placebo	Active comparator	Placebo, the same constituents as Zemplar (propylene glycol 30% (v/v) alcohol 20% (v/v)) but no paricalcitol, same dosage as verum-arm. Receives: Drug: Placebo (for paricalcitol)

What is being measured

The primary outcome is the main question the study is designed to answer.

change in IL-10 production from baseline
Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and after 4 weeks of treatment comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.
Measured: baseline and 4 weeks of treatment
change in IL-10 production from baseline
Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and at follow-up (between 5-7 weeks) comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.
Measured: baseline and follow-up visit (between 5-7 weeks)

Secondary outcomes (64)

Change in IgE responses to birch pollen compared to baseline
IgE responses to birch pollen measured in serum by ImmunoCAPwill be compared between subjects treated with Vitamin D3 or placebo
Measured: Baseline compared to 4 weeks of treatment
To evaluate the number of patients that reported adverse events with Zemplar compared to placebo. This includes adverse measurements in blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function compared to placebo.
To evaluate the number of patients that reported adverse events with the VD3 analogue Zemplar® compared to placebo. This includes adverse measurements in blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function compared to placebo.
Measured: Throughout the study and follow-up (a maximum total of 8 weeks)
changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: Baseline compared to 4 weeks of treatment
changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: baseline and follow-up visit (between 5-7 weeks)
changes in percentage Th2 cells characterized by the expression of CD4, CRTh2, CCR4 and Gata-3, compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: Baseline compared to 4 weeks of treatment
changes in percentage Th2 cells characterized by the expression of CD4, CRTh2, CCR4 and Gata-3, compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: baseline and follow-up visit (between 5-7 weeks)
changes in percentage Th17/Th22 cells characterized by the expression of CD4, CCR6, CCR4, CCR10 and RORc2 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: Baseline compared to 4 weeks of treatment
changes in percentage Th17/Th22 cells characterized by the expression of CD4, CCR6, CCR4, CCR10 and RORc2 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: baseline and follow-up visit (between 5-7 weeks)
changes in percentage Treg cells characterized by the expression of CD4, CD25, CD127, and Foxp3 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: Baseline compared to 4 weeks of treatment
changes in percentage Treg cells characterized by the expression of CD4, CD25, CD127, and Foxp3 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: baseline and follow-up visit (between 5-7 weeks)
changes in percentage B cells characterized by the expression of CD19, CD5, CD20, CD27, and CD38 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: Baseline compared to 4 weeks of treatment
changes in percentage B cells characterized by the expression of CD19, CD5, CD20, CD27, and CD38 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: baseline and follow-up visit (between 5-7 weeks)
changes in percentage antigen presenting cells characterized by the expression of CD11c, HLA-DR, CD14, CD16, CD1c, CD141, CD123, CD19, CD163, CD68, CD86 and CD83 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: Baseline compared to 4 weeks of treatment
changes in percentage antigen presenting cells characterized by the expression of CD11c, HLA-DR, CD14, CD16, CD1c, CD141, CD123, CD19, CD163, CD68, CD86 and CD83 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to enhance T-cell proliferation compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by allergen and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to enhance T-cell proliferation compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by allergen and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-5 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-5 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-17 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-17 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-10 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-10 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce TGF-b compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce TGF-b compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to enhance T-cell proliferation compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to enhance T-cell proliferation compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-5 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-5 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-17 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-17 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IFN-y, compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-10 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-10 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce TGF-b compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce TGF-b compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-4 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-4 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-9 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-9 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-17A compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-17A compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Measured: baseline and follow-up visit (between 5-7 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2015Oct 2016

First posted22 Feb 2016 (estimated)
Study startOct 2015
Primary completionApr 2016
Study completionOct 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HypersensitivityStudies 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 2
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02686827
Sponsor's protocol ID: BM4SIT
Acronym: BM4SIT
Status last verified: Aug 2018
First submitted: 28 Jan 2016
Last updated: 4 Sep 2018
Results posted: No
Data monitoring committee: Yes
Individual data sharing: Undecided: The investigators have to discuss this within theEU project.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Placebo-controlled Study to Determine the Immune Effects of Multiple Doses of Vitamin D3 in Patients With Allergic Rhinitis/Rhino-conjunctivitis Caused by Birch Pollen and in Healthy Control Subjects.
ClinicalTrials.gov ID: NCT02686827
Acronym / sponsor ID: BM4SIT / BM4SIT
Conditions: Hypersensitivity
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: Laurian JongejanUniversity, hospital or other
Study start: Oct 2015
Primary completion: Apr 2016 (actual)
Study completion: Oct 2016 (actual)
First posted: 22 Feb 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Paricalcitol (Vitamin D3)	Experimental	Drug: Paricalcitolparicalcitol, (Zemplar® 5 μg/ml Abbvie), will be administered via the subcutaneous route 4 times at 0.5 ml (registered dose of 5 μg/ml, thus 2.5 μg per sub-cutaneous injection). The minimum time interval between two injections is 4 days, which is a significantly lower frequency than the prescribed maximum of 3 times a week or every other day.
Placebo	Active comparator	Drug: Placebo (for paricalcitol)Placebo, the same constituents as Zemplar (propylene glycol 30% (v/v) alcohol 20% (v/v)) but no paricalcitol, same dosage as verum-arm.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (8 listed)

Signed informed consent
Age ≥18 ≤ 60 years
Allergic rhinitis/rhino-conjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma based on relative symptoms and allergy tests.
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 OR a positive serum specific anti-birch IgE-test (>0.7 U/ml)
Signed informed consent

Key exclusion criteria (18 listed)

A history of allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) within the 5 years before inclusion/screening visit.
Treatment with parenteral Vitamin D3 analogue in the year before inclusion
Significant, ongoing nasal symptoms caused by other allergens at study onset
A history of Hypercalcemia, Hypophosphatemia or vitamin D toxicity
Any vaccination within one week before randomization

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
ParicalcitolAlso: Vitamin D3, (Zemplar)Vitamin D3 analogue	Drug	Paricalcitol (Vitamin D3)
Placebo (for paricalcitol)Also: fluid to mimic paricalcitol injectionInjection fluid to mimic paricalcitol injection	Drug	Placebo

Primary outcome

change in IL-10 production from baseline
Time frame: baseline and 4 weeks of treatment
Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and after 4 weeks of treatment comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.
change in IL-10 production from baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and at follow-up (between 5-7 weeks) comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.

64 secondary outcomes

Change in IgE responses to birch pollen compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
To evaluate the number of patients that reported adverse events with Zemplar compared to placebo. This includes adverse measurements in blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function compared to placebo.
Time frame: Throughout the study and follow-up (a maximum total of 8 weeks)
changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
changes in percentage Th2 cells characterized by the expression of CD4, CRTh2, CCR4 and Gata-3, compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
changes in percentage Th2 cells characterized by the expression of CD4, CRTh2, CCR4 and Gata-3, compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
changes in percentage Th17/Th22 cells characterized by the expression of CD4, CCR6, CCR4, CCR10 and RORc2 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
changes in percentage Th17/Th22 cells characterized by the expression of CD4, CCR6, CCR4, CCR10 and RORc2 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
changes in percentage Treg cells characterized by the expression of CD4, CD25, CD127, and Foxp3 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
changes in percentage Treg cells characterized by the expression of CD4, CD25, CD127, and Foxp3 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
changes in percentage B cells characterized by the expression of CD19, CD5, CD20, CD27, and CD38 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
changes in percentage B cells characterized by the expression of CD19, CD5, CD20, CD27, and CD38 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
changes in percentage antigen presenting cells characterized by the expression of CD11c, HLA-DR, CD14, CD16, CD1c, CD141, CD123, CD19, CD163, CD68, CD86 and CD83 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
changes in percentage antigen presenting cells characterized by the expression of CD11c, HLA-DR, CD14, CD16, CD1c, CD141, CD123, CD19, CD163, CD68, CD86 and CD83 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to enhance T-cell proliferation compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to enhance T-cell proliferation compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-5 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-5 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-13 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-13 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-17 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-17 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-10 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-10 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-21 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-21 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-22 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-22 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IFN-y compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IFN-y compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce TGF-b compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated with Bet v 1, to produce TGF-b compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to enhance T-cell proliferation compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to enhance T-cell proliferation compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-5 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-5 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-13 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-13 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-17 compared to baseline
Time frame: Baseline compared to 4 weeks of treatment
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-17 compared to baseline
Time frame: baseline and follow-up visit (between 5-7 weeks)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2018.
Individual participant dataSharing planned: Undecided. The investigators have to discuss this within theEU project.

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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.

Wytske J Fokkens, Prof MD PhD principal investigator

Academic Medical Centre

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Paricalcitol in people with Hypersensitivity, run by Laurian Jongejan at 1 site in Netherlands.

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 8 inclusion and 18 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 4 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 in IL-10 production from baseline (time frame: baseline and 4 weeks of treatment). 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?

On the ClinicalTrials.gov record for NCT02686827.

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 4 Sep 2018.