Allergy, Immune Tolerance, Injection Site Discomfort
Conditions
Keywords
Allergic Rhinitis, Allergen immunotherapy
Brief summary
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
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.
Interventions
DRUGAlk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.
4
DRUGalk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.
3 injection into a lymphnode
DRUG0.1 ml Isoton saline
4 injection into a lymphnode
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cSMS (Combined Symptom and Medication Score) | 3 years | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Change in Circulating Grass Specific Immunoglobulin E Producing Plasmacells | one week from vaccinations |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Basophil Sensitivity | 2 years | Flowcytometry based analysis of basophil cells reaction to allergen provocation. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intralymphatic Immune Therapy 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.
Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 4 | 12 |
| 3 Intralymphatic Immune Therapy 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.
alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 3 injection into a lymphnode | 12 |
| no Intralymphatic Immune Therapy 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.
0.1 ml Isoton saline: 4 injection into a lymphnode | 12 |
| Total | 36 |
Baseline characteristics
| Characteristic | Intralymphatic Immune Therapy | 3 Intralymphatic Immune Therapy | no Intralymphatic Immune Therapy | Total |
|---|---|---|---|---|
| Age, Continuous | 31.67 years STANDARD_DEVIATION 5.52 | 29.92 years STANDARD_DEVIATION 6.8 | 30.58 years STANDARD_DEVIATION 7.43 | 30.72 years STANDARD_DEVIATION 6.58 |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 7 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 12 | 5 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: 3 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intralymphatic Immune Therapy | Change in cSMS (Combined Symptom and Medication Score) | 2.6 score on a scale |
| 3 Intralymphatic Immune Therapy | Change in cSMS (Combined Symptom and Medication Score) | 2.3 score on a scale |
| no Intralymphatic Immune Therapy | Change in cSMS (Combined Symptom and Medication Score) | 4.5 score on a scale |
Secondary
Change in Circulating Grass Specific Immunoglobulin E Producing Plasmacells
Time frame: one week from vaccinations
Population: Due to technical flow-cytometry problem could analysis of circulating grass specific immunoglobulin E producing plasma cells not be performed.
Other Pre-specified
Change in Basophil Sensitivity
Flowcytometry based analysis of basophil cells reaction to allergen provocation.
Time frame: 2 years
Population: Due to technical problems data was not recorded at all time points and results are missing.