Effect of Intralymphatic Immunotherapy

Study Overview
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Brief Summary
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The investigators want to investigate whether specific immunotherapy can be delivered directly into a lymph node. The investigators think that a direct introduction of allergen to the antigen presenting cells in the lymph node a give a strong immune response and that this can change the number of injections needed in allergen immunotherapy. The investigators do measurements of clinical effect and a variety of paraclinical test to see if the investigators can find af biomarker of successful specific immune therapy of grass allergy.

Detailed Description
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Patients are injected with 3 or 4 doses of alk 225 Phleum Pratense 1000 standard quantity units/ml in a lymph node in the groin. The investigators monitor clinical response and use of medication during the grass pollen season. SMS (Symptom and Medication Score) will be used. The investigators count the number of immunoglobulin E grass producing plasma cells in blood one week after each injection. The investigators also do basophil activation tests, nasal provocation tests and titrated skin prick test to monitor effect. Adverse events will be recorded.

Official Title
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Effect of Intralymphatic Immunotherapy at Basophil Response and Plasmacell Kinetic in Patients With Allergic Rhinitis.

Conditions
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Allergy, Immune Tolerance, Injection Site Discomfort

Intervention / Treatment
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* Drug: Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.
* Drug: alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.
* Drug: 0.1 ml Isoton saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Allergic rhinitis to grass pollen, more than 3 mm reaction at skin prick test for grass, age between 18 and 40 years. Exclusion Criteria: Uncontrolled asthma. Severe asthma with post bronchodilator test forced expiratory volume at 1 second less than 70% of expected. Severe co morbidity. Allergy to Fenol or Aluminium hydroxid. Any autoimmune diseases. Treatment with beta blocking medicine. Any heart diseases. Severe arterial hypertension. Kidney failure. Known malignancy. Known pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: intralymphatic immune therapy<br>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml. Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. | Drug: Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.<br>* 4<br>|
| Placebo Comparator: 3 intralymphatic immune therapy<br>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml. Patients receive 3 injection in total. 3 injection in the spring 2014 with one month interval. In in the spring 2015 patients will have a placebo injection. | Drug: alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.<br>* 3 injection into a lymphnode<br>|
| Sham Comparator: no intralymphatic immune therapy<br>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of isotone saline. Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. All injections are with isotone saline as placebo control. | Drug: 0.1 ml Isoton saline<br>* 4 injection into a lymphnode<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cSMS (Combined Symptom and Medication Score) | cSMS, Combined symptom and medication score, during grass pollen season in three years follow up. Minimal score 0, Maximal score 18. Higher score means worse outcome. Scale: Itchy/red eys: 0-3, Runny eyes: 0-3, Itchy nose: 0-3, Runny nose: 0-3, Block nose: 0-3, Sneezes: 0-3. Topical antihistamine 1.5 points/1 point. Nasal corticosteroid: 1 point/2 points. Oral antihistamine: 6 points/1 point. Oral prednisolon 1.5 point /3 points. Elements are summed to a combined score. Different combination methods exists. EAACI recommends means, i.e. symptoms 0-3 plus medicationscore 0-3. This scoringsystem was applied in the last follow-up year. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Circulating Grass Specific Immunoglobulin E Producing Plasmacells |  | one week from vaccinations | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allergic Rhinitis, Allergen immunotherapy