Pilot Study of Intralymphatic Immunotherapy (ILIT) for House Dust Mite, Cat, and Dog Allergen in Allergic Rhinitis

Allergic Rhinitis Clinical Trial

— pILIT  

Official title:

Open-labeled Pilot Study of Intralymphatic Immunotherapy (ILIT) for House Dust Mite, Cat, and Dog Allergen in Allergic Rhinitis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02301884
• Other study ID #: GBIRB2013-35
• Status: Completed
• Phase: Phase 1
• First received: November 24, 2014
• Last updated: March 10, 2015
• Start date: November 2013
• Est. completion date: March 2015

Study information

• Verified date: March 2015
• Source: Gachon University Gil Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The investigators performed open-labeled pilot study 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.

Description:

After informed consent, causal allergen was injected into inguinal lymph node through guidance by ultrasonography three times with 4-week interval. Initial dose of allergen was 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. After the first dose, allergen concentration was escalated 3-fold at second dose, and 10-fold at third dose if there was no or mild local or systemic hypersensitivity reaction. The allergen concentration did not change at second or third dose if there was moderate local or systemic reaction. The allergen concentration was decreased by 10 or 100-fold from previous concentration if there was severe local or systemic reaction.

The investigators evaluated parameters regarding allergic rhinitis within a week before the first injection and 4 months after the first injection. These parameters included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Sino-Nasal Outcome Test (SNOT-20), and 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. Skin prick test, intradermal test, blood sampling for serum allergen-specific IgE, exhaled nitric oxide, and nasal lavage for Th1, Th2, and Treg cytokines were also included. Adverse events were recorded and graded according to Muller's classification and Ring and Messmer's classification.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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, immunosuppressant 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Allergic Rhinitis
• Rhinitis

Intervention

Biological:
• Allergen extract
Causal allergen extract such as D. farinae, D. pteronyssinus, cat hair, dog hair/dander, or combination of those

Locations

Country	Name	City	State
Korea, Republic of	Gachon University Gil Medical Center	Incheon

Sponsors (2)

Lead Sponsor	Collaborator
Gachon University Gil Medical Center	Thermo Fisher Scientific

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (8)

Hylander T, Latif L, Petersson-Westin U, Cardell LO. Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis. J Allergy Clin Immunol. 2013 Feb;131(2):412-20. doi: 10.1016/j.jac — View Citation

Kündig TM, Johansen P, Bachmann MF, Cardell LO, Senti G. Intralymphatic immunotherapy: time interval between injections is essential. J Allergy Clin Immunol. 2014 Mar;133(3):930-1. doi: 10.1016/j.jaci.2013.11.036. Epub 2014 Jan 15. — View Citation

Senti G, Crameri R, Kuster D, Johansen P, Martinez-Gomez JM, Graf N, Steiner M, Hothorn LA, Grönlund H, Tivig C, Zaleska A, Soyer O, van Hage M, Akdis CA, Akdis M, Rose H, Kündig TM. Intralymphatic immunotherapy for cat allergy induces tolerance after onl — View Citation

Senti G, Johansen P, Kündig TM. Intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol. 2009 Dec;9(6):537-43. doi: 10.1097/ACI.0b013e3283310ff7. Review. — View Citation

Senti G, Johansen P, Kündig TM. Intralymphatic immunotherapy: from the rationale to human applications. Curr Top Microbiol Immunol. 2011;352:71-84. doi: 10.1007/82_2011_133. Review. — View Citation

Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ, Simard JJ, Wüthrich B, Crameri R, Graf N, Johansen P, Kündig TM. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. — View 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. — View Citation

Zaleska A, Eiwegger T, Soyer O, van de Veen W, Rhyner C, Soyka MB, Bekpen C, Demiröz D, Treis A, Söllner S, Palomares O, Kwok WW, Rose H, Senti G, Kündig TM, Ozoren N, Jutel M, Akdis CA, Crameri R, Akdis M. Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine. Allergy. 2014 Sep;69(9):1162-70. doi: 10.1111/all.12461. Epub 2014 Jul 12. Erratum in: Allergy. 2016 Jan;71(1):129. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RQLQ	Rhinoconjunctivitis Quality of Life Questionnaire	Baseline and 4 months after the first injection	No
Secondary	SNOT-20	Sino-Nasal Outcome Test-20	Baseline and 4 months after the first injection	No
Secondary	Skin reactivity	Allergen/histamine ratio of mean wheal diameter in skin prick test, and allergen/saline ratio of mean wheal diameter in intradermal test	Baseline and 4 months after the first injection	No
Secondary	Serum total and allergen-specific IgE and IgG4 level	Serum total and allergen-specific IgE and IgG4 level using UNICAP, Thermofisher Scientific, Sweden	Baseline and 4 months after the first injection	No
Secondary	Nasal reactivity	Symptom score and volume 2-6 cm in acoustic rhinometry during nasal provocation test with D. farinae and/or D. pteronyssinus in allergic rhinitis patients sensitized to house dust mite	Baseline and 4 months after the first injection	No
Secondary	Cytokines in nasal lavage fluid	Cytokines of Th1, Th2, and Treg in nasal lavage fluid	Baseline and 4 months after the first injection	No
Secondary	Exhaled NO	Exhaled nitric oxide measuring NIOX MINO, Thermofisher Scientific, Sweden	Baseline and 4 months after the first injection	No
Secondary	Respiratory and dermatologic symptoms provoked by allergen exposure in daily life	Visual analogue scale of respiratory and dermatologic symptoms provoked by allergen exposure in daily life (ranged from 0 to 100)	Baseline and 4 months after the first injection	No