Personalized Treatment Algorithms for Difficult-to-treat Asthma

• Sponsor: Children's Hospital Medical Center, Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT04179461
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arm: 1
• Actual Duration (Months): 18.6
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma in Children	Drug: Cholecalciferol; Drug: antihistamine; Drug: Azithromycin; Drug: emollient cream; Drug: Fluticasone Propionate; Drug: Asthma Controller Medication	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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.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)
• Primary Purpose: Treatment
• Official Title: Personalized Treatment Algorithms for Difficult-to-treat Asthma: Bench to Community
• Actual Study Start Date: Mar 16, 2018
• Actual Primary Completion Date: Oct 3, 2019
• Actual Study Completion Date: Oct 3, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Personalized Treatment 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; Oral administration; Other Names: Vitamin D ; Drug: antihistamine; Oral administration; Other Names: cetirizine loratadine ; Drug: Azithromycin; Oral administration; Other Names: Zithromax ; Drug: emollient cream; Topical; Drug: Fluticasone Propionate; Nasal spray; Other Names: Flonase Nasal Spray ; Drug: Asthma Controller Medication; Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.; Other Names: Mometasone/Formoterol Fluticasone/Salmeterol Mometasone Furoate Fluticasone Beclomethasone Budesonide/Formoterol Tiotropium

Outcome Measures

Primary Outcome Measures

1. Change in Composite Asthma Severity Index (CASI) [Baseline to 12 months]

   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]

Secondary Outcome Measures

1. Asthma Control Test (ACT) [Baseline to 12 months]

   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]

2. Pulmonary Function Measured by Spirometry: Forced Expiratory Volume in 1 Second (FEV1) / Forced Vital Capacity (FVC) [Baseline to 12 months]

   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]

3. Adherence of Asthma Controller Medication [Baseline to 12 months]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• Children's Hospital Medical Center, Cincinnati

Investigators

• Principal Investigator: Theresa Guilbert, MD, Children's Hospital Medical Center, Cincinnati
• Principal Investigator: Gurjit K Khurana Hershey, MD, PhD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 19, 2019

More Information

Publications

None provided.

• Responsible Party: Theresa Guilbert, MD, Principal Investigator, Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT04179461
• Other Study ID Numbers: ARC 7
• First Posted: Nov 27, 2019
• Last Update Posted: Aug 20, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Asthma; Vitamin D; Cholecalciferol; Fluticasone; Xhance; Mometasone Furoate; Cetirizine; Loratadine; Azithromycin; Budesonide; Beclomethasone; Emollients; Formoterol Fumarate; Tiotropium Bromide; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Histamine Antagonists; Histamine H1 Antagonists

Study Results

Participant Flow

Arm/Group Title	Personalized Treatment
Arm/Group Description	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. Cholecalciferol: Oral administration antihistamine: Oral administration Azithromycin: Oral administration emollient cream: Topical Fluticasone Propionate: Nasal spray Asthma Controller Medication: Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.
Period Title: Overall Study
STARTED	21
COMPLETED	17
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Personalized Treatment
Arm/Group Description	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. Cholecalciferol: Oral administration antihistamine: Oral administration Azithromycin: Oral administration emollient cream: Topical Fluticasone Propionate: Nasal spray Asthma Controller Medication: Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.
Overall Participants	20
Age (Count of Participants)
<=18 years	20 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.4 (2.8)
Sex: Female, Male (Count of Participants)
Female	9 45%
Male	11 55%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	14 70%
White	6 30%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	20 100%
Primary home within a 40 mile radius of Cincinnati Children's Base Location (Count of Participants)
Count of Participants [Participants]	20 100%
Health insurance coverage at enrollment (Count of Participants)
Count of Participants [Participants]	20 100%

Outcome Measures

1. Primary Outcome

Title	Change in Composite Asthma Severity Index (CASI)
Description	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]
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

17 participants whom had complete data sets were analyzed. 4 participants withdrew early from the study and were not included in this analysis due to incomplete data.

Arm/Group Title	Personalized Treatment
Arm/Group Description	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. Cholecalciferol: Oral administration antihistamine: Oral administration Azithromycin: Oral administration emollient cream: Topical Fluticasone Propionate: Nasal spray Asthma Controller Medication: Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.
Measure Participants	17
V1	5
V2	5
V3	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Personalized Treatment
	Comments	The modified CASI score incorporates key asthma outcomes such as symptoms, healthcare utilization, and medication dose.
	Type of Statistical Test	Equivalence
	Comments	The Wilcoxon signed-rank test was employed for pairwise comparison between visits for continuous data. Data for the CASI was captured at clinical visits. 3. A level of statistical significance was established at < 0.05.
Statistical Test of Hypothesis	p-Value	0.52
	Comments	Change in CASI score from V1 to V3
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Asthma Control Test (ACT)
Description	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]
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

17 participants whom had complete data sets were analyzed. 4 participants withdrew early from the study and were not included in this analysis due to incomplete data.

Arm/Group Title	Personalized Treatment
Arm/Group Description	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. Cholecalciferol: Oral administration antihistamine: Oral administration Azithromycin: Oral administration emollient cream: Topical Fluticasone Propionate: Nasal spray Asthma Controller Medication: Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.
Measure Participants	17
V1	23.0
V2	21.7
V3	22.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Personalized Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	The Wilcoxon signed-rank test was employed for pairwise comparison between visits for continuous data. Data for the c-ACT/ACT was captured at clinical visits and from monthly phone calls. Because c-ACT/ACT could vary through time, we calculated the average c-ACT/ACT between V1-V2 and V2-V3. Data analysis was performed in SAS version 9.4 (SAS, Cary, NC). A level of statistical significance was established at < 0.05.
Statistical Test of Hypothesis	p-Value	0.45
	Comments	The change in ACT score from V1 to V2 (the period between V1 and V2).
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Personalized Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	The Wilcoxon signed-rank test was employed for pairwise comparison between visits for continuous data. Data for the c-ACT/ACT was captured at clinical visits and from monthly phone calls. Because c-ACT/ACT could vary through time, we calculated the average c-ACT/ACT between V1-V2 and V2-V3. Data analysis was performed in SAS version 9.4 (SAS, Cary, NC). A level of statistical significance was established at < 0.05.
Statistical Test of Hypothesis	p-Value	0.01
	Comments	The change in ACT score from V1-V2 to V2-V3.
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Pulmonary Function Measured by Spirometry: Forced Expiratory Volume in 1 Second (FEV1) / Forced Vital Capacity (FVC)
Description	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]
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

17 participants whom had complete data sets were analyzed. 4 participants withdrew early from the study and were not included in this analysis due to incomplete data.

Arm/Group Title	Personalized Treatment
Arm/Group Description	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. Cholecalciferol: Oral administration antihistamine: Oral administration Azithromycin: Oral administration emollient cream: Topical Fluticasone Propionate: Nasal spray Asthma Controller Medication: Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.
Measure Participants	17
V1	0.81
V2	0.8
V3	0.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Personalized Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	The Wilcoxon signed-rank test was employed for pairwise comparison between visits for continuous data and the Bowker's test was used to compare categorical FEV1-FVC data. Data analysis was performed in SAS version 9.4 (SAS, Cary, NC). A level of statistical significance was established at < 0.05.
Statistical Test of Hypothesis	p-Value	0.27
	Comments	The Change in FEV1/FVC from Visit 1 to Visit 3
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Adherence of Asthma Controller Medication
Description	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).
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

16 participants whom had complete data sets were analyzed.

Arm/Group Title	Personalized Treatment
Arm/Group Description	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. Cholecalciferol: Oral administration antihistamine: Oral administration Azithromycin: Oral administration emollient cream: Topical Fluticasone Propionate: Nasal spray Asthma Controller Medication: Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.
Measure Participants	16
V1	42
V3	36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Personalized Treatment
	Comments
	Type of Statistical Test	Equivalence
	Comments	Intervention adherence and end of study adherence were each calculated based on the 30 days prior to end of intervention and V3, respectively, in order to assess a consistent timeframe. The paired Wilcoxon signed rank test was conducted to compare controller inhaler adherence during baseline, adherence intervention, and end of study.
Statistical Test of Hypothesis	p-Value	0.17
	Comments	Change between baseline (V1) to end of study (V3)
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Review for possible adverse events was completed at study visits and follow-up phone calls by the research coordinator. If adverse events were identified, they were documented on the Adverse Event Reporting Form and reviewed at the meeting of the Steering committee.
Arm/Group Title	Personalized Treatment
Arm/Group Description	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. Cholecalciferol: Oral administration antihistamine: Oral administration Azithromycin: Oral administration emollient cream: Topical Fluticasone Propionate: Nasal spray Asthma Controller Medication: Study participants asthma controller medication may be increased based off of their asthma control and the recommendation of the personalized plan.
All Cause Mortality
	Personalized Treatment
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Serious Adverse Events
	Personalized Treatment
	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)
Psychiatric disorders
Major Depressive Disorder	1/21 (4.8%)	1
Psychiatric Evaluation	1/21 (4.8%)	2
Other (Not Including Serious) Adverse Events
	Personalized Treatment
	Affected / at Risk (%)	# Events
Total	12/21 (57.1%)
Infections and infestations
Influenza	2/21 (9.5%)	2
Streptococcal Pharyngitis	3/21 (14.3%)	3
Viral Gastroenteritis	2/21 (9.5%)	2
Sinusitis	1/21 (4.8%)	2
Musculoskeletal and connective tissue disorders
Ankle Injury	2/21 (9.5%)	2
Respiratory, thoracic and mediastinal disorders
Asthma Exacerbation	8/21 (38.1%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.