Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00367016
Status:
COMPLETED
Last Update Posted:
2021-07-13
First Post:
2006-08-19
Brief Title:
Immunologic Basis of Anti-IgE Therapy Study II On Patients With Asthma
Sponsor:
University of California Davis
Organization:
University of California Davis
Study Overview
Official Title:
Immunologic Basis of Anti-IgE Therapy Study II On Patients With Asthma
Status:
COMPLETED
Status Verified Date:
2021-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Xolair
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 FcεRIICD23 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 FcεRIICD23 on B cells Because of the demonstrated function of FcεRIICD23 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
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 FcεRIICD23 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 FcεRIICD23 on B cells Because of the demonstrated function of FcεRIICD23 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None