Clinical trial NCT02676765
Conditions: Immunologic Desensitization
Keywords: Allergic rhinitis Immunotherapy, Allergen Sublingual Immunotherapy
Sponsor: Virginia Commonwealth University
Start date: 2016-06-01; Completion date: 2018-01-18
Enrollment: 58 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine if sublingual allergen immunotherapy tablets work by inducing a state of desensitization in mast cells and basophils.

Detailed description:
To induce clinical tolerance, a failure to respond to an allergen to which one was previously responsive, is an important objective for physicians, one that plays a significant role in the primary prevention of allergic reactions in the clinical practice of Allergy \& Immunology. The tolerance resulting after standard subcutaneous immunotherapy to aeroallergen and insect venom allergens is long lasting and allergen-specific, and may involve antigen-specific T regulatory cells. In contrast, tolerance resulting from drug desensitization protocols is short-lived, and postulated to target mast cells and basophils. Research into the cellular and biochemical processes by which desensitization occurs has revealed that mast cells desensitized to one antigen in vitro, under certain conditions, lose the ability to degranulate to unrelated antigens or to direct FcεRI cross-linking. Preliminary data suggests that this cross-desensitization can happen in patients undergoing incremental desensitization, depending in part on the percentage of IgE targeted to the allergen used for desensitization. This proposal therefore aims to explore desensitization and cross-desensitization in human volunteers undergoing standard sublingual (SL) immunotherapy to grass or ragweed pollen.

Subjects will undergo SL immunotherapy with either Timothy or Short Ragweed tablets, taking one tablet per day, or will take a placebo tablet. Titration skin testing to Timothy or Short Ragweed, to one or preferably two additional allergens to which the subject is sensitive, and to codeine as a control for mast cell activation capability through a non-IgE-dependent pathway will be performed to determine the PC3 value (see below). Skin testing, including histamine and diluent controls, will be performed prior to and at one and four weeks after initiation of immunotherapy. At each time point, blood will be obtained to measure total and antigen-specific IgE levels, tryptase and cytokine levels, and basophil activation with the relevant allergens and C5a as a non-IgE-mediated control for basophil activation.

Arms: arm 1: Subjects will be administered a sublingual allergen tablet customized to their individual allergic sensitization. arm 2: Subjects will be administered placebo sublingual tablets
Interventions: intervention 1: allergen extract tablet intervention 2: Placebo tablet
Intervention descriptions: intervention 1: 1 allergen extract tablet, placed under the tongue until dissolved, taken daily; do not swallow for 1 minute after placing tablet; do not eat or drink for 5 minutes after placing tablet intervention 2: 1 placebo tablet, placed under the tongue until dissolved, taken daily; do not swallow for 1 minute after placing tablet; do not eat or drink for 5 minutes after placing tablet

Protocol documents:
Prot_SAP_000.pdf: