Clinical trial NCT02269566: Intralymphatic Immunotherapy (ILIT) for House Dust Mite, Cat, and Dog Allergen in Allergic Rhinitis Patients
Official title: A Double-blinded Placebo-controlled Randomized Clinical Trial Evaluating the Efficacy and Adverse Effect of Intralymphatic Immunotherapy (ILIT) for House Dust Mite, Cat, and Dog Allergen in Allergic Rhinitis Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Allergic Rhinitis
Keywords: allergic rhinitis
immunotherapy
Lead sponsor: Gachon University Gil Medical Center
Sponsor class: OTHER
Collaborators: name: Thermo Fisher Scientific, Inc
First posted: 2014-10-21
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We will perform double-blinded placebo-controlled randomized clinical trial which evaluates the efficacy and safety of allergen-specific intralymphatic immunotherapy (ILIT) for allergens including Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), cat, and dog that are sensitized and provoke rhinitis-related symptoms in patients with allergic rhinitis.

Detailed description: After informed consent, subjects will be randomly assigned to ILIT group or placebo group in double-blind manner. In both group, causal allergen or placebo will be injected into inguinal lymph node through guidance by ultrasonography three times with 4-week interval. In ILIT group, initial dose of allergen will be 1,000-fold diluted solution from maximal concentration of allergen extract for subcutaneous immunotherapy (30 AU/ml for Df or Dp, 10 AU/ml for Cat hair, and 1:1/10 weight/volume for dog hair/dander, HollisterStier, New Orleans, USA) in volume of 0.1ml. If skin is highly reactive in skin prick test, the initial dose will be 10-fold dilution from maximal concentration where diameter of wheal is less than that of histamine. After the first dose, allergen concentration will be escalated 3-fold at second dose, and 10-fold at third dose if there are no local or systemic hypersensitivity reaction. The allergen concentration will not change at second or third dose if there is mild local or systemic reaction. The allergen concentration will decrease by 10 or 100-fold from previous concentration or further injection will be holded if there is severe local or systemic reaction after sufficient explanation and discussion with subjects.

The investigators will evaluate allergic rhinitis symptom score before and 4, 12 months after the initial treatment. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Sino-Nasal Outcome Test (SNOT-20) will be used. Visual analogue scale (VAS) of symptoms including rhinorrhea, sneezing, nasal obstruction, postnasal drip, eye/nose/ear/palate itching, dyspnea, wheezing, chest discomfort as well as urticaria, angioedema, and itching on exposed skin during exposure to causal allergen in daily life will be also evaluated. Skin prick test, intradermal test, blood sampling for serum allergen-specific IgE, exhaled nitric oxide, and nasal lavage for Th1, Th2, and Treg cytokines will be also performed before and 4, 12 months after the initial treatment.

Adverse events will be recorded and graded according to Muller classification and Ring and Messner classification.

Eligibility criteria: Inclusion Criteria:

* Allergic rhinitis to house dust mite (Df, Dp), cat or dog
* More than 3mm reaction at skin prick test for Df, Dp, cat or dog or more than class 3 at serum specific IgE level (UNICAP or MAST)

Exclusion Criteria:

* Uncontrolled or severe asthma according to Global Initiative of Asthma (GINA) guideline
* FEV1 less than 50% of predicted value if there is comorbid asthma.
* Subject rejects the enrollment into study
* Low compliance
* Pregnancy or lactation
* Significant cardiovascular, hepatic, renal, hematologic, oncologic, or infectious diseases
* Administration of beta blocker, angiotensin converting enzyme inhibitor, tricyclic antidepressant, immnosuppressant including systemic glucocorticosteroid (20mg or more dose of prednisolone or equivalent dose of other steroid) within last 2 weeks
* Prior history of allergen-specific immunotherapy
* Allergic rhinitis caused by other perennial or seasonal allergen
* Vulnerable volunteer

Primary outcomes:
measure: Rhinoconjunctivitis Quality of Life Questionnaire
timeFrame: up to 12 months after the initial treatment
Secondary outcomes:
measure: SNOT-20
timeFrame: before and 4, 12 months after the initial treatment
measure: Skin reactivity
timeFrame: before and 4, 12 months after the initial treatment
measure: Serum alllergen-specific IgE level
timeFrame: before and 4, 12 months after the initial treatment
measure: Nasal reactivity
timeFrame: before and 4, 12 months after the initial treatment
measure: Cytokines in nasal lavage fluid
timeFrame: before and 4, 12 months after the initial treatment
measure: Exhaled NO
timeFrame: before and 4, 12 months after the initial treatment
measure: Allergic rhinitis symptoms during allergen exposure in daily life
timeFrame: before and 4, 12 months after the initial treatment
Other outcomes:
Locations:
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
Study officials:
affiliation: Gachon University Gil Medical Center
name: Sang Min Lee, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Witten M, Malling HJ, Blom L, Poulsen BC, Poulsen LK. Is intralymphatic immunotherapy ready for clinical use in patients with grass pollen allergy? J Allergy Clin Immunol. 2013 Nov;132(5):1248-1252.e5. doi: 10.1016/j.jaci.2013.07.033. Epub 2013 Sep 13. No abstract available.
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