Immunologic Basis of Anti-IgE Therapy (Study II: On Patients With Asthma)

NCT ID: NCT00367016

Last Updated: 2021-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2012-10-17

Brief Summary

The purpose of this study is to look at measures that will help scientists understand the way Omalizumab, an FDA-approved anti-allergy medication, works.

Detailed Description

IgE is a key molecule involved in immediate hypersensitivity and plays a major role in the pathogenesis of allergic diseases. Recently, a therapy based on the use of anti-IgE antibody has been developed by a pharmaceutical company, Genentech. A number of clinical trials have demonstrated that these antibodies are efficacious in treatment of allergies, including allergic rhinitis and asthma. The medication Omalizumab (Xolair) has recently been approved by the FDA for treatment of asthma.

The mechanism underlying the beneficial effect of this therapy is not completely understood, but is likely to be related to the marked reduction in the IgE level. Of note is the concomitant accumulation of IgE-anti-IgE complexes in the sera. Another remarkable effect of the treatment is the substantial reduction in the FcεRI level on basophils, which is likely a key factor contributing to the therapeutic benefit of the drug. The existing literature suggests that the reduction in the IgE level is likely to result in a down-regulation of another IgE receptor, FcεRII/CD23. Because of the known immunomodulatory function of FcεRII, anti-IgE therapy may result in alterations of the immune system, in addition to simple absorption of IgE.

We propose to conduct mechanistic studies of anti-IgE therapy. The objectives are to address how anti-IgE therapy works and how it might affect the immune system in general. The proposed studies also take advantage of this well-defined therapy to address some basic questions regarding the immune system. Our hypothesis is that anti-IgE therapy may have general effects on the immune system, such as reduced IgE-mediated antigen presentation by antigen-presenting cells and suppressed allergen-specific IgE and IgG production. The specific aims of the proposed research are:

1. Determination of the effect of anti-IgE therapy on FcεRI expression and basophil responses. We will first confirm that anti-IgE therapy causes a reduction in the FcεRI level on basophils and then analyze whether this occurs at a transcriptional level. We will confirm that the therapy causes a reduction in basophil response to cross-linkage of FcεRI and then determine whether it also affects basophil response induced by non-IgE stimuli. The effect of the therapy on the FcεRI level on skin mast cells will also be investigated.

2. Determination of the effect of anti-IgE therapy on FcεRII expression and antigen presentation. We will determine whether the therapy results in a down-regulation of FcεRII/CD23 on B cells. Because of the demonstrated function of FcεRII/CD23 in antigen presentation, we will determine the antigen presentation to T cells by B cells from anti-IgE-treated and control subjects.

3. Determination of the effect of anti-IgE therapy on antibody production. We will determine whether anti-IgE therapy results in a suppression of IgE production, in addition to sequestration of IgE. Whether IgE-anti-IgE complexes directly suppress IgE production by B cells in vitro will be investigated.

Conditions

Asthma; Allergic Rhinitis; Atopic Dermatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Omalizumab

Subjects will receive subcutaneous Omalizumab for 6 months. Prior to Omalizumab administration, all subjects will undergo screening studies, including spirometry, blood test and skin test. Blood test includes comprehensive metabolic panel, CBC, and total and free IgE levels. Skin test will be done with a panel of 7 common allergens

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: DRUG

Xolair (Omalizumab) will be given by subcutaneous injection according to Ige level and weight calculation.

Placebo

Subjects will receive subcutaneous placebo for 6 months. Prior to placebo administration, all subjects will undergo screening studies, including spirometry, blood test and skin test. Blood test includes comprehensive metabolic panel, CBC, and total and free IgE levels. Skin test will be done with a panel of 7 common allergens

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo, given by subcutaneous injection.

Interventions

Omalizumab

Xolair (Omalizumab) will be given by subcutaneous injection according to Ige level and weight calculation.

Intervention Type: DRUG

Placebo

Placebo, given by subcutaneous injection.

Intervention Type: DRUG

Other Intervention Names

Xolair

Eligibility Criteria

Inclusion Criteria

• Mild or moderate persistent asthma
• Allergic rhinitis
• Atopic dermatitis

Exclusion Criteria

• Other lung diseases
• Blood clotting disorder
• Pregnant or lactating women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fu-Tong Liu, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

UC Davis Department of Dermatology

Sacramento, California, United States

Countries

United States

Related Links

http://www.ucdmc.ucdavis.edu/dermatology/research/clinical

University of California-Davis Department of Dermatology Clinical Research

Other Identifiers

200312064

Identifier Type: -

Identifier Source: org_study_id