Effect of Intralymphatic Immunotherapy

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

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.

Study Overview

• Status: Completed
• Conditions: Allergy; Immune Tolerance; Injection Site Discomfort
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Lungemedicinsk Forskningsafdeling. Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.; 4
Placebo Comparator: 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.	Drug: alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.; 3 injection into a lymphnode
Sham Comparator: 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.	Drug: 0.1 ml Isoton saline; 4 injection into a lymphnode

What is the study measuring?

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	Time Frame
Change in Circulating Grass Specific Immunoglobulin E Producing Plasmacells	one week from vaccinations

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Basophil Sensitivity	Flowcytometry based analysis of basophil cells reaction to allergen provocation.	2 years

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Søren Helbo SH Skaarup, MD, Lungemedicinsk forskningsafdeling. Aarhus University Hospital.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: September 17, 2014
• First Submitted That Met QC Criteria: September 29, 2014
• First Posted (Estimate): October 2, 2014

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Allergic Rhinitis; Allergen immunotherapy
• Other Study ID Numbers: ILIT