Protocol CAUSE-03 / CHEETAH (CHEETAH)

Mechanisms Underlying Asthma Symptoms and Exacerbations Examined Across T2 Status in Children (CHEETAH) (CAUSE-03)

This is a one-year longitudinal, observational study of 250 urban children and adolescents with asthma and 60 without asthma, ages 6-17 years old.

Participants with asthma will require daily controller therapy with inhaled corticosteroids ICS (at least Step 2 therapy). Those without asthma cannot have used asthma medications in the year prior to enrollment and cannot demonstrate bronchodilator reversibility at baseline. Phenotypic characteristics will be established at baseline, and the participants will be seen at scheduled visits over 12 months. Each participant will be asked to monitor and self-report cold symptoms and will be asked to complete up to three cold visits

Study Overview

• Status: Recruiting
• Conditions: Asthma

• Study Type: Observational
• Enrollment (Estimated): 310

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado: Allergy Program
      • Contact: Pascuala Pinedo-Estrada; Phone Number: 720-777-8077; Email: pascuala.pinedo-estrada@childrenscolorado.org
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's National Medical Center: Children's Research Institute
      • Contact: Nia Moore; Phone Number: 202-476-3488; Email: nmoore3@childrensnational.org
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago: Division of Allergy and Immunology
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Boston Children's Hospital: Department of Immunology
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston University School of Medicine: Pulmonary Center
      • Contact: Nicole Gonzalez; Phone Number: 617-358-7626; Email: nicolegg@bu.edu
  • New York
    • New York, New York, United States, 10029
      • Not yet recruiting
      • Icahn School of Medicine at Mount Sinai: Division of Clinical Immunology, Immunology Institute
    • New York, New York, United States, 10032
      • Not yet recruiting
      • Columbia University Medical Center: Division of Pediatric Pulmonology
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Not yet recruiting
      • Cincinnati Children's Hospital Medical Center: Asthma Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Approximately 250 urban children and adolescents with asthma (requiring daily controller therapy with Inhaled corticosteroid (ICS) (at least Step 2 therapy) and approximately 60 urban children and adolescents without asthma

Description

Inclusion Criteria:

1. Participant and/or parent guardian must be able to understand and provide informed consent and assent

2. Have a primary place of residence in one of the pre-selected recruitment census tracts as outlined in the Protocol CAUSE-03 Manual of Operations (MOP)

   a. Participants who do not live in the pre-selected census tracts but live within the Office of Management and Budget (OMB) defined Metropolitan Statistical Area and have publicly funded health insurance will qualify for inclusion

3. Either:

   1. Have had a diagnosis of asthma made > 1 year prior to recruitment; participants who received an asthma diagnosis by a clinician <= 1 year prior to recruitment must report that their respiratory symptoms were present for more than 1 year prior to recruitment (asthma group), or
   2. No report of ever being diagnosed with asthma (non-asthma group)

4. Either:

   1. Require at least Step 2 therapy at the Screening/Enrollment Visit (asthma group), or
   2. Have not used any asthma medications in the prior year (non-asthma group)
5. Are able to perform acceptable and repeatable spirometry per American Thoracic Society (ATS) criteria prior to enrollment
6. Have documentation of current medical insurance with prescription coverage at the Screening/Enrollment Visit
7. Participant and/or parent guardian has a smartphone compatible with the study electronic Patient Reported Outcomes (ePRO) system, Medidata Patient Cloud, and is willing to download one application for study use

Exclusion Criteria:

1. Parent or guardian is not able or willing to give written informed consent or comply with study protocol
2. Have concurrent medical problems that would require systemic corticosteroids or other immunomodulators during the study
3. Are currently receiving immunotherapy
4. Are currently receiving treatment with a biologic therapy or have received a biologic therapy within 3 months prior to enrollment
5. Are currently requiring greater than fluticasone 500 mcg bid plus Long-Acting Beta Agonists (LABA) one puff twice daily or its equivalent plus Long Acting Muscarinic Antagonists (LAMA) and/or individuals using oral corticosteroids daily or every other day for more than 14 days at the time of the Screening/Enrollment Visit
6. Are currently pregnant or lactating, or plan to become pregnant during the time of study participation. Females of child-bearing potential (post-menarche) must be abstinent or use a medically acceptable birth control method throughout the study (i.e., oral subcutaneous, mechanical, or surgical contraception)
7. Have a known, pre-existing clinically important lung condition other than asthma.
8. Have a current malignancy or previous history of cancer in remission for less than 12 months prior to enrollment
9. Have a known immunodeficiency disease
10. Use of investigational drugs within 4 weeks of enrollment
11. Have past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
12. If in the asthma group, will not allow the study clinician, an asthma specialist, to manage their disease for the duration of the study or who are not willing to change their asthma medications to follow Protocol CAUSE-03 CHEETAH
13. If in the non-asthma group, having bronchodilator reversibility (improvement in Forced expiratory volume in 1 second (FEV1) with albuterol > = 10%) at the Screening/Enrollment visit
14. Have had a life-threatening asthma exacerbation in the last 2 years requiring intubation, mechanical ventilation or resulting in a hypoxic seizure. Potential participants may be reassessed as outlined in the Protocol CAUSE-03 Manual of Procedures (MOP)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Asthma group; Participants ages 6 to 17 year old in the asthma group will be seen in clinic quarterly for one year, during periods of disease control when they are not on systemic corticosteroids (SCS)
Non-asthma group; Participants in the non-asthma group will be seen at two scheduled visits in clinic at 3 and 12 months and will have telephone visits at 6 and 9 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Asthma disease activity measured by the number of exacerbations during the 12-month observation period	Month 0 to Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Childhood Asthma Severity Index (CASI)	measured on a scale from 0 to 20 with smaller scores indicate a better outcome.	Month 0 to Month 12
Modified Rhinitis Symptom Utility Index (MRSUI)	measured by assessing the frequency and severity (degree of bothering: not bothered, somewhat bothered, bothered a lot) of the participant's (1) stuffy or blocked nose, (2) runny nose, (3) sneezing, (4) itchy, watery eyes, and (5) itchy nose or throat over the preceding 14-day period	Month 0 to Month 12
Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K)	measured on a scale from 0 to 42 with higher scores indicating a worse outcome (high symptoms and high functional impairment)	Month 0 to Month 12
Quality of life measured by the pediatric patient-reported (ages 8-17) or proxy-reported (ages 6-7) Patient-Reported Outcomes Measurement Information System (PROMIS) Asthma Impact Short Forms	The outcome measure is a score on a scale from 8 - 40 with higher scores indicating a worse outcome (more severe asthma symptoms).	Month 0 to Month 12
Post-bronchodilator forced expiratory volume in 1 second (FEV1) for asthma group		Month 3 to Month 12
Post-bronchodilator forced expiratory volume in 1 second (FEV1) for non-asthma group		At Month 0
Post-bronchodilator forced vital capacity (FVC) for asthma group		Month 3 to Month 12
Post-bronchodilator forced vital capacity (FVC) for non-asthma group		At Month 0
Bronchodilator reversibility asthma group in the asthma group, measured by the percent change in FEV1 with albuterol		Month 3 to Month 12
Bronchodilator reversibility in the non-asthma group, measured by the percent change in FEV1 with albuterol		At Month 0

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Andrew Liu, M.D., Children's Hospital Colorado: Allergy Program; Study Chair: Matthew C. Altman, M.D., M.Phil., Benaroya Research Institute at Virginia Mason: Systems Immunology Division

Publications and helpful links

Helpful Links

• Division of Allergy, Immunology, and Transplantation
• National Institute of Allergy and Infectious Diseases

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: October 16, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 9, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Asthma; Children; Observational study
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma
• Other Study ID Numbers: DAIT CAUSE-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
• IPD Sharing Time Frame: On average, within 24 months after database lock for the trial.
• IPD Sharing Access Criteria: Open access.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No