mRNA Expression as a Biomarker of Omalizumab Response

Study Overview
=================
Brief Summary
-----------------
Objectives: 1. Determine if mRNA expression could be use as a biomarker to predict and monitor the response to omalizumab in patients with difficult control asthma 2. Identify which genes are switched on and which are switched off by using Omalizumab. Methods: This study is an open label clinical trial, with six patients. The patients will receive Omalizumab according to their age and weight (maximum dose: 375 mg every 15 days) for 4 months. There will be a run-in period of one month, when allergic asthma diagnosis will be confirmed and treatment will be optimized. Patients will be evaluated and will have blood sample collected on 3 occasions: in the beginning, 2 months after baseline and at the end of the study. Blood samples will always be collected one week after the last omalizumab dose. Primary outcome will be RNA expression of 20 genes measured by real time-PCR (high-affinity IgE receptor, IL-4, IL-5, IL-13, gama-IFN, quimokines, Fc epsilon, between others). Secondary outcomes will be ACT, ACQ and spirometry.

Detailed Description
-----------------
Study rational: There is not a biomarker that can predict which patients will respond to Omalizumab and those who will not respond. Nowadays, the monitoring of therapeutic response to Omalizumab is based on clinical and spirometric data. On the other hand, when a medication is administered, it has its main expected effect, but also acts on other targets with various direct and indirect effects. We do not know all the genes that are switched on and those that are switched off by the use of Omalizumab. For example, anti-IgE has been developed to block serum total IgE and thereby improve control of allergic asthma. However, the studies noted that Omalizumab also reduces the receptors FcepsilonRI, which may have implications for the treatment of autoimmune urticaria.

Official Title
-----------------
mRNA Expression as a Biomarker of Xolair (Omalizumab) Response

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Biological: Omalizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: over 12 years severe asthma not controlled despite medication IgE between 70 and 1300 IU/ml and evidence of allergy clinical history and/or skin test or blood. Exclusion Criteria: previous use of omalizumab smoke history

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omalizumab<br>All patients will receive omalizumab. | Biological: Omalizumab<br>* The patients will receive Omalizumab according to their age and weight for 4 months.<br>* Other names: Xolair;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of mRNA expression in leukocytes (real time-PCR) | Patients will be evaluated and will have blood sample collected on 3 occasions: in the beginning, 2 months after baseline and at the end of the study. Blood samples will always be collected one week after the last omalizumab dose. Primary outcome will be RNA expression of 30 genes measured by real time-PCR. | At the end of the study (4months after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the scores of questionnaires of asthma control | Patients will be evaluated on 3 occasions: in the beginning, 2 months after baseline and at the end of the study. Secondary outcomes will be the scores of Asthma Control Test and Asthma Control Questionnaire. | At the end of the study (4 months after baseline) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
asthma, difficult-to-control asthma, mRNA expression, biomarker, real time PCR, ACT, ACQ