Xolair Interventional Study in ASD Patients With Comorbid Atopy

Study Overview
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Brief Summary
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Following the publication of two case studies that reported behavioral benefit in ASD patients treated with omalizumab, the investigators will conduct a pilot trial to test the proof-of-concept efficacy of omalizumab in ASD patients with comorbid atopic disease. Investigators will evaluate behavioral improvement using three questionnaires. Investigators will also perform fMRI on all subjects and obtain serum samples for quantification of immunological biomarkers. If the trial is conclusive, the investigators will conduct a larger-scale, randomized-controlled trial to further understand the pathology of allergy in this subpopulation of ASD patients and the efficacy of this intervention.

Detailed Description
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This clinical trial is a Phase I, single-arm, open-label study. All 20 subjects will be given the same dosage of the study drug. Following baseline testing, subjects will undergo treatment during a 24 week treatment period and will receive six subcutaneous injections total, one injection every 4 weeks. A 24-week follow-up period after the treatment period will be concluded with patient interview. Behavioral questionnaires will be administered throughout the duration of the trial. fMRI will be conducted at baseline and at the conclusion of the treatment period. Blood will be drawn for serum testing at baseline, at Week 12 during the treatment period, and at the conclusion of the treatment period. Vitals and CGI will also be assessed throughout the trial.

Official Title
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The Effect of Omalizumab (Xolair) on Improving Neuropsychiatric Symptoms in a Subset of ASD Patients With Atopic Disease and Elevated Total IgE Levels

Conditions
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Autism Spectrum Disorder, Atopy

Intervention / Treatment
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* Drug: Omalizumab Injection [Xolair]


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age between 18-30 years old. Clinical diagnosis of ASD during childhood that is still active. History of atopic diseases, including asthma, atopic dermatitis, and allergic rhinitis. Total serum IgE level ≥ 30 IU/ml and ≤ 400 IU/ml Exclusion criteria: History of omalizumab use. Subjects who have used oral or systemic steroid burst within 6 weeks of study enrollment. Subjects who are receiving a maintenance dose of Prednisone of 5 mg/day or less will be allowed provided the dose of Prednisone is not changed during the study. Subjects actively taking the antipsychotic medication, Loxapine. History of cancer or pre-cancer. Subjects with active or unstable seizure disorder. History or active signs of psychosis. Body weight > 90kg For subjects who meet allergic rhinitis inclusion criteria, RCAT >20 IQ < 70 Adaptive Behavior Composite score < 90, based on the Vineland 3rd Edition Lactating or pregnant females. Xolair has not been sufficiently tested for safe use in pregnant females. Subjects who are deemed by the study staff to be unable to cooperate with or understand the instructions that will be given during the study. Subjects with severe medical condition(s) that in the view of a Physician Investigator prohibits participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Baseline testing, followed by 24-week treatment period, followed by 24-week follow-up period.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Subjects will receive subcutaneous treatment of 300mg of omalizumab during the 24-week treatment period. One injection will be administered every 4 weeks. | Drug: Omalizumab Injection [Xolair]<br>* 300mg via 2 subcutaneous injections every 4 weeks<br>* Other names: Xolair;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 12 in Social Responsiveness Scale (SRS) Edition 2 | Social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD). | Baseline and Week 12 | 
| Change from Baseline to Week 24 in Social Responsiveness Scale (SRS) Edition 2 | Social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD). | Baseline and Week 24 | 
| Change from Baseline to Week 48 in Social Responsiveness Scale (SRS) Edition 2 | Social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD). | Baseline and Week 48 | 
| Change from Week 24 to Week 48 in Social Responsiveness Scale (SRS) Edition 2 | Social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD). | Week 24 (conclusion of treatment period) and Week 48 (follow-up) | 
| Change from Baseline to Week 12 in Aberrant Behavior Checklist (ABC) | Social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -not at all a problem, 1- the behavior is a problem but slight in degree, 2- the problem is moderately serious and 3- the problem is severe in degree. Based on this sub-scores are calculated and added to get the total score. | Baseline and Week 12 | 
| Change from Baseline to Week 24 in Aberrant Behavior Checklist (ABC) | Social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -not at all a problem, 1- the behavior is a problem but slight in degree, 2- the problem is moderately serious and 3- the problem is severe in degree. Based on this sub-scores are calculated and added to get the total score. | Baseline and Week 24 (conclusion of treatment period) | 
| Change from Baseline to Week 48 in Aberrant Behavior Checklist (ABC) | Social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -not at all a problem, 1- the behavior is a problem but slight in degree, 2- the problem is moderately serious and 3- the problem is severe in degree. Based on this sub-scores are calculated and added to get the total score. | Baseline and Week 48 (follow-up) | 
| Change from Week 24 to Week 48 in Aberrant Behavior Checklist (ABC) | Social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -not at all a problem, 1- the behavior is a problem but slight in degree, 2- the problem is moderately serious and 3- the problem is severe in degree. Based on this sub-scores are calculated and added to get the total score. | Week 24 (conclusion of treatment period) and Week 48 (follow-up) | 
| Change from Baseline to Week 1 in Autism Treatment Evaluation Checklist (ATEC) | Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity. | Baseline and Week 1 | 
| Change from Baseline to Week 4 in Autism Treatment Evaluation Checklist (ATEC) | Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity. | Baseline and Week 4 | 
| Change from Baseline to Week 8 in Autism Treatment Evaluation Checklist (ATEC) | Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity. | Baseline and Week 8 | 
| Change from Baseline to Week 12 in Autism Treatment Evaluation Checklist (ATEC) | Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity. | Baseline and Week 12 | 
| Change from Baseline to Week 16 in Autism Treatment Evaluation Checklist (ATEC) | Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity. | Baseline and Week 16 | 
| Change from Baseline to Week 20 in Autism Treatment Evaluation Checklist (ATEC) | Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity. | Baseline and Week 20 | 
| Change from Baseline to Week 24 in Autism Treatment Evaluation Checklist (ATEC) | Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity. | Baseline and Week 24 (conclusion of treatment period) | 
| Change from Baseline to Week 48 in Autism Treatment Evaluation Checklist (ATEC) | Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity. | Baseline and Week 48 (follow-up) | 
| Change from Week 24 to Week 48 in Autism Treatment Evaluation Checklist (ATEC) | Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity. | Week 24 (conclusion of treatment period) and Week 48 (follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory Marker Levels | Inflammatory marker serum concentration quantification (free IgE, total IgE, interleukin 6, tumor necrosis factor alpha, tryptase). | Baseline, Week 12, and Week 24 (conclusion of treatment period) | 
| Structural MRI | The software Freesurfer will be used to calculate volume of brain regions and diffusion parameters (e.g. fractional anisotropy and mean diffusivity) from structural T1 and diffusion tensor images respectively. Paired t-test will be used to compare brain volume at baseline and post-treatment. | Baseline and Week 24 (conclusion of treatment period) | 
| Functional MRI (resting state) | Correlation analysis will be used to calculate the connectivity across different brain regions. Paired t-test will be used to compare differences in activity at baseline and post-treatment. | Baseline, and Week 24 (conclusion of treatment period) | 
| Generalized Anxiety Disorder 7-item (GAD-7) | Anxiety symptom questionnaire - Scoring is based on how frequently the subject experienced 7 GAD-related symptoms in the last two weeks. Each question is rated on a 0-3 scale: 0 - Not at all, 1 - Several days, 2 - More than half the days, 3 - Nearly every day. Defined cutoffs will be used to define severity. | Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) | 
| Epworth Sleepiness Scale (ESS) | Sleepiness Questionnaire - Scoring is based on how likely the subject is to doze off or fall asleep during 8 daily activities. Higher scores indicate more severe sleepiness. | Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) | 
| Pittsburgh Sleep Quality Index (PSQI) | Sleep Quality Questionnaire - Scoring is based on 19 self-administered questions and 5 roommate questions. An algorithm provided with the questionnaire will be used to calculate global sleep quality score, for which a higher score indicates greater severity. | Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) | 
| Asthma Control Test (ACT) | A 5 question patient survey designed to identify patients with poorly controlled asthma based on the symptom severity over the last 4 weeks. | Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) | 
| Rhinitis Control Assessment Test (RCAT) | A 6 question patient survey designed to evaluate rhinitis symptom control based on symptom severity and frequency over the past week. | Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) | 
| Validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) | A clinical assessment tool used to describe severity of atopic dermatitis. The vIGA-AD includes a single scale from 0-4, in which 0 is clear and 4 is severe. | Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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omalizumab