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

Allergic Rhinitis Clinical Trial

— ILIT  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02269566
• Other study ID #: 20140101480
• Status: Terminated
• Phase: Phase 1
• First received: October 17, 2014
• Last updated: August 10, 2016
• Start date: August 2014
• Est. completion date: March 2016

Study information

• Verified date: August 2016
• Source: Gachon University Gil Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: March 2016
• Est. primary completion date: February 2016
• 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, 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Allergic Rhinitis
• Rhinitis
• Rhinitis, Allergic

Intervention

Drug:
• HollisterStier
0.1 ml of 30 AU/ml for Df or Dp, 10 AU/ml for Cat hair, and/or 1:1/10 weight/volume for dog hair/dander 3 injections into an inguinal lymph node
• Normal saline
0.1 ml of normal saline 3 injections into an inguinal lymph node

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 (9)

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.jaci.2012.10.056. — 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

Martínez-Gómez JM, Johansen P, Erdmann I, Senti G, Crameri R, Kündig TM. Intralymphatic injections as a new administration route for allergen-specific immunotherapy. Int Arch Allergy Immunol. 2009;150(1):59-65. doi: 10.1159/000210381. Epub 2009 Apr 2. — 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 only 3 injections. J Allergy Clin Immunol. 2012 May;129(5):1290-6. doi: 10.1016/j.jaci.2012.02.026. Epub 2012 Mar 30. — 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, 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. Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17908-12. doi: 10.1073/pnas.0803725105. Epub 2008 Nov 10. — View Citation

von Moos S, Kündig TM, Senti G. Novel administration routes for allergen-specific immunotherapy: a review of intralymphatic and epicutaneous allergen-specific immunotherapy. Immunol Allergy Clin North Am. 2011 May;31(2):391-406, xi. doi: 10.1016/j.iac.2011.02.012. Review. — 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	Rhinoconjunctivitis Quality of Life Questionnaire		up to 12 months after the initial treatment	No
Secondary	SNOT-20	Sino-Nasal Outcome Test	before and 4, 12 months after the initial treatment	No
Secondary	Skin reactivity	Diameters of wheal provoked by causal allergens in skin prick test and intradermal test	before and 4, 12 months after the initial treatment	No
Secondary	Serum alllergen-specific IgE level	Serum alllergen-specific IgE level using UNICAP, Thermofisher Scientific, Sweden	before and 4, 12 months after the initial treatment	No
Secondary	Nasal reactivity	Threshold concentration in nasal provocation test for allergens of Df and Dp	before and 4, 12 months after the initial treatment	No
Secondary	Cytokines in nasal lavage fluid	Cytokines of Th1, Th2, and Treg in nasal lavage fluid	before and 4, 12 months after the initial treatment	No
Secondary	Exhaled NO	Exhaled nitric oxide measuring NIOX MINO, Thermofisher Scientific, Sweden	before and 4, 12 months after the initial treatment	No
Secondary	Allergic rhinitis symptoms during allergen exposure in daily life	Visual analog scare of allergic rhinitis symptoms during allergen exposure in daily life	before and 4, 12 months after the initial treatment	No