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

NCT ID: NCT02686827

Last Updated: 2018-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2016-10-31

Brief 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.

Conditions

Hypersensitivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

Paricalcitol (Vitamin D3)

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.

Group Type: EXPERIMENTAL

Paricalcitol

Intervention Type: DRUG

Vitamin D3 analogue

Placebo

Placebo, the same constituents as Zemplar (propylene glycol 30% (v/v) alcohol 20% (v/v)) but no paricalcitol, same dosage as verum-arm.

Group Type: ACTIVE_COMPARATOR

Placebo (for paricalcitol)

Intervention Type: DRUG

Injection fluid to mimic paricalcitol injection

Interventions

Paricalcitol

Vitamin D3 analogue

Intervention Type: DRUG

Placebo (for paricalcitol)

Injection fluid to mimic paricalcitol injection

Intervention Type: DRUG

Other Intervention Names

Vitamin D3, (Zemplar); fluid to mimic paricalcitol injection

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent

2. Age ≥18 ≤ 60 years

3. Allergic rhinitis/rhino-conjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma based on relative symptoms and allergy tests.

4. 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)

1. Signed informed consent

2. Age, gender and location matched to a study subject. An age matched control is defined as the age of the study subject ±5 years.

3. No history of respiratory allergies and no nasal symptoms at screening.

4. 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.

Exclusion Criteria

1. A history of allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) within the 5 years before inclusion/screening visit.

2. Treatment with parenteral Vitamin D3 analogue in the year before inclusion

3. Significant, ongoing nasal symptoms caused by other allergens at study onset

4. A history of Hypercalcemia, Hypophosphatemia or vitamin D toxicity

5. Any vaccination within one week before randomization

6. 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

7. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs

8. Uncontrolled asthma or other active respiratory diseases

9. Malignancies or any malignant disease during the previous 5 years

10. 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

11. Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study

12. Use of preparations containing calcium or magnesium such as thiazide, diuretics, antacides.

13. Use of systemic steroids within 4 weeks before screening and during the study

14. Daily use of ketoconazole cream or immunosuppressive creams at planned injection site less than 7 days before or during the study

15. 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)

16. Any clinically significant abnormal laboratory parameter at screening

17. Any physical or mental condition that precludes compliance or participation in a clinical trial

18. Subjects who are employees or students of the institution or 1st grade relatives or partners of the investigators

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Laurian Jongejan

OTHER

Sponsor Role: lead

Responsible Party

Laurian Jongejan

Project manager

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Wytske J Fokkens, Prof MD PhD

Role: PRINCIPAL_INVESTIGATOR

Academic Medical Centre

Locations

Academic medical center

Amsterdam, , Netherlands

Countries

Netherlands

Other Identifiers

BM4SIT

Identifier Type: -

Identifier Source: org_study_id