Intralymphatic Immunotherapy Enhanced by Vitamin-D, a Randomized Placebo-controlled Trial and Comparison With SLIT

Study Overview
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Brief Summary
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A national, multicenter, randmised double blind study with parallell arms. 360 patients with grass induced allergic rhinitis will be open randomised 1:2 to 3 years Grazax sublingual immunotherapy or 3 intralymphatic injections with ALK Alutard Timothy. In a second step, the ILIT group will be double blind randomised 1:1 to an intramuscular injection of Vitamin D Vicotrat or placebo, 4 week before the start of the intralymphatic treatment. The primary outcome measure is daily combined symptoms and medication scores during grass pollen season.

Official Title
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Sublingual Immunotherapy Compared to Intralymphatic Immunotherapy With Concomitant Vitamin D, a Randomised Placebo Controlled Study

Conditions
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Allergic Rhinitis Due to Grass Pollen

Intervention / Treatment
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* Drug: SLIT Grazax ALK Nordic 75 000 SQ-T
* Drug: ILIT + Vitamin D
* Drug: ILIT + placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: moderate to severe allergic rhinitis due to grass pollen, with Rhinitis Total Symptom Score >/= 8. informed consent Exclusion Criteria: chronic rhinosinusitis Previous immunotherapy BMI > 35 house dust mite allergy with symptoms or allergy towards furry animals with exposition 25(OH)Vitamin D levels < 25 or > 75 nmol/L uncontrolled asthma severe atopic dermatitis pregnancy or nursing autoimmune disease hyper IgE-syndrome cardiovascular disease lung disease liver or kidney disease hematologic disorder metabolic disease chronic infectious disese medications interacting with the immune system cancer previous cytostatic therapy medication with beta-blockers or ACE-inhibiters, if medication cannot be paused at the day for treatment medication with antiepileptic drugs, glykosides, orlistat, statines, thiazide diuretics Mb Paget, osteoporosis or sarcidosis Hyperparathyroidism or other disease conferring risk of hypercalcemia malabsorption or bowel disease with diarrea tendency for formation of kidney stones hereditary pseudohypoparathyroidism with decreased phosphorous secretion use of Vitamin D supplementation or excessive use of sun tanning booths drug abuse intake of other study product within 1 month or 6 half times, which ever is longest, before visit 1 Mental incapacity to follow study protocol withdrawn consent other significant disease allergy towards study medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SLIT<br>Sublingual immunotherapy timothy pollen 75000 SQ-T 1 daily for 3 years | Drug: SLIT Grazax ALK Nordic 75 000 SQ-T<br>* Daily sublingual grass allergen tablets<br>|
| Active Comparator: ILIT + Vitamin D<br>Intramuscular injection of kolecalciferol 100000 IU followed by intralymphatic immunotherapy with 3 monthly injections of grass pollen allergen 1000 SQ-U. | Drug: ILIT + Vitamin D<br>* 1 mL of Vicotrat D3, Heyl Pharma, 100 000 IU/mL, as intramuscular injection. Followed by 0,1 mL of Alutard SQ timothy, ALK Nordic, 10 000 SQ-U/mL as three intralymphatic injections<br>* Other names: Alutard SQ timothy and Vicotrat D3;|
| Active Comparator: ILIT + placebo<br>Intramuscular injection of saline solution followed by intralymphatic immunotherapy with 3 monthly injections of grass pollen allergen 1000 SQ-U. | Drug: ILIT + placebo<br>* 1 ml of Sodium chloride solution 9 mg/mL as intramuscular injection followed by 0,1 mL of Alutard SQ timothy, ALK Nordic, 10 000 SQ-U/mL as three intralymphatic injections<br>* Other names: Alutard SQ timothy and Sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSMS | Daily Combined Symptoms and Medication Scores (0-3) | 60-75 days at the grass pollen season year 1; 4 months before treatment. 60-75 days year 2; 6 months after start of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSMS peak pollen season | Daily Combined Symptoms and Medication Scores (0-3) during the 15 consecutive days with the highest pollen count | 15 days at the grass pollen season year 1; 4 months before treatment. 15 days year 2; 6 months after start of treatment. | 
| RQLQ | Juniper Rhinoconjunctivitis Quality of Life Questionnaire, weekly scores (0-28) | 60-75 days at the grass pollen season year 1; 4 months before treatment. 60-75 days year 2; 6 months after start of treatment. | 
| VAS (0-10) | Recalled symptoms severity at visual analogue scale | 4-6 months before treatment and 6-9 months after treatment | 
| Serolology with immunoglobulins | Total and grass specific levels of IgE, IgG, IgG4, IgA in serum | 1 year before treatment, 4-6 weeks after treatment, 1 year after treatment |