Personalized Treatment Algorithms for Difficult-to-treat Asthma

Study Overview
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Brief Summary
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Asthma is a common, complex and costly chronic condition. Moreover, asthma is heterogeneous in terms of treatment response. This heterogeneity contributes to the difficulty in both studying and treating asthma. This is a pilot study to improve health outcomes in youths with difficult to treat asthma with ongoing symptoms and healthcare utilization despite medium to high doses of inhaled corticosteroids. Asthma heterogeneity in both disease pathophysiology and treatment response contributes to the difficulty in both studying and managing asthma. In order to begin to develop personalized algorithms for patients, investigators need to model novel biomarkers and other factors that contribute to individual differences in asthma outcome and test other factors that contribute to individual differences in asthma outcome and test personalized treatment strategies.

Detailed Description
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With this study investigators will conduct study visits to determine and quantify known molecular, genetic, genomic, epigenetics, immunologic, and exposure biomarkers that will help elucidate molecular disease endotype within the difficult-to-treat phenotype. This information will be used along with clinical, psychosocial, and adherence data to develop a personalized treatment plan. Following the personalized treatment plan, study clinicians will prescribe the medications through a home delivery or routine pharmacy depending on the family's preference and covered by the participant's health insurance. Investigators will track disease outcome metrics including exacerbations, symptom-free days, and asthma symptom scores to determine the effectiveness of this personalized approach.

Official Title
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Personalized Treatment Algorithms for Difficult-to-treat Asthma: Bench to Community

Conditions
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Asthma in Children

Intervention / Treatment
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* Drug: Cholecalciferol
* Drug: antihistamine
* Drug: Azithromycin
* Drug: emollient cream
* Drug: Fluticasone Propionate
* Drug: Asthma Controller Medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of provider-diagnosed asthma Meets one of the following definition for NAEPP guidelines uncontrolled moderate persistent asthma or severe persistent asthma in the past 12 months: NAEPP step 3-4 with one of the following criteria in the past 12 months: Two Asthma Control Test (ACT) scores <20 1 Urgent Care or Emergency Department visit or hospitalization for asthma >2 prednisone bursts NAEPP step 5-6 Current health insurance coverage at enrollment. This will be verified at V1 at the registration desk. If the family loses insurance during the study, the patient will be referred to the pulmonary social worker and financial office for assistance Reside at a primary home on average 5 out of 7 days a week. Primary home is within a 40 mile radius of Cincinnati Children's Base location or PI's discretion. Exclusion Criteria: Received biologic therapy 6 months prior to enrollment Received systemic steroids 6 weeks prior to enrollment Active chronic disease apart from asthma or allergic disease Co-morbid lung disease Dependence on immunosuppressive drugs for a condition other than asthma Participant is pregnant Has a severe bleeding disorder Has significant developmental disability Share a bedroom with a currently enrolled Breath Warriors study participant

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: The study has 3 study phases: baseline, intervention, and observation. Each participant will independently transition through these study phases. Baseline period: Each participant will be given a treatment recommendation according to their asthma severity/control using the National Asthma Education and Prevention Program (NAEPP asthma guidelines). Intervention period: Each participant will be given a personalized treatment plan based on their asthma severity/control during the baseline period, biologic, and environmental factors. Observation period: All participants will be observed for at least 6 months. Investigators will track the participant's personal outcomes (comparing to baseline) for reutilization, symptom-free days, and quality of life.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Personalized Treatment<br>Personalized asthma treatment plan based off of individual's asthma severity/control, personal and family medical history, history of environmental exposures, adherence, medical visits, biomarker assays, and home trigger assessment. Study participants were prescribed recommended medications for the treatment of their asthma. These medications were prescribed through their insurance based of the of personalized treatment plan recommendation. Asthma controller medications may be increased based off of the participant's asthma control and the recommendation of the personalized plan. They would receive one of the asthma controller medications listed in the intervention. | Drug: Cholecalciferol<br>* Oral administration<br>* Other names: Vitamin D;Drug: antihistamine<br>* Oral administration<br>* Other names: loratadine;Drug: Azithromycin<br>* Oral administration<br>* Other names: Zithromax;Drug: emollient cream<br>* Topical<br>Drug: Fluticasone Propionate<br>* Nasal spray<br>* Other names: Flonase Nasal Spray;Drug: Asthma Controller Medication<br>* Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.<br>* Other names: Tiotropium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Composite Asthma Severity Index (CASI) | CASI was measured by questionnaire and is a severity score of symptom burden, exacerbations, healthcare utilization, lung function and dose of inhaled corticosteroids. The change in CASI score was calculated between V1 (Baseline), V2 (Guideline Care - before intervention), and V3 (12 Months). [The CASI score has a minimum value = 0, maximum value = 20, a higher score indicates greater asthma severity] | Baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Control Test (ACT) | ACT was measured by questionnaire, assessing frequency of reported asthma symptoms, rescue medication use, the effect of asthma on daily functioning, and overall asthma control. The change in ACT score was calculated between V1 (Baseline), V2 (Guideline Care - before intervention), and V3 (12 Months). [The ACT score has a minimum value = 5, maximum value = 25, a score 19 indicates well-controlled asthma] | Baseline to 12 months | 
| Pulmonary Function Measured by Spirometry: Forced Expiratory Volume in 1 Second (FEV1) / Forced Vital Capacity (FVC) | FEV1 is air volume exhaled in 1 second during spirometry. Forced vital capacity is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. The change in FEV1/FVC was calculated between V1 (Baseline), V2 (Guideline Care - before intervention), and V3 (12 Months). This will be used as a measurement in asthma severity. [A lower FEV1/FVC ratio indicates more severe asthma] | Baseline to 12 months | 
| Adherence of Asthma Controller Medication | Adherence was measured using the Propeller Health Inhaler monitor and web-based software management platform that tracks adherence of asthma medications. The change in adherence was calculated between V1 (baseline) to V3 (12 Months). | Baseline to 12 months |