Oxidative Stress in Asthma

• Status: Recruiting
• Trial end date: 2025-01-01
• Target enrollment: 0
• Participant gender: All

Summary

40% of all asthma patients in the US are obese. Obese asthmatics have more severe disease than lean asthmatics and do not respond as well to conventional anti-inflammatory therapies. This proposal will utilize 3D functional imaging with 129XeMRI and single cell RNA sequencing to study mechanisms driving regional airway remodeling and fibrosis in obese asthma subjects and in preclinical models of obese asthma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Bastiaan Driehuys
• Collaborator: National Institutes of Health (NIH)

Criteria

Inclusion Criteria:

Asthma Cohort INCLUSION

• Adequate completion of informed consent process with written documentation

• Male and female patients, 18 - 65 years old, inclusive

• Physician diagnosis of asthma for > 1 year

• Able to perform reproducible spirometry according to ATS criteria

• Post-bronchodilator FEV1 ≥ 60% of predicted at Visit 0

• All racial/ethnic backgrounds may participate

• BMI ≥ 30 kg/m2

• Regular treatment with ICS or ICS/LABA and/or LAMA combination medication for at least 3 months; on a stable dose for the 4 weeks prior to Visit 0

• Smoking history <10 pack years and no smoking in the last 3 months

• Late onset asthma: Age of asthma onset (diagnosis) ≥12 years;

• FeNO < 25 ppb at Visit 0

• Negative allergen skin test

• Early onset asthma: Age of asthma onset (diagnosis) <12 years

• FeNO ≥ 25 ppb at Visit 0

• Positive allergen skin test

Non-Asthma Cohort INCLUSION

• No history of asthma or other chronic lung diseases

• Male and female patients, 18 - 65 years old, inclusive

• Not currently smoking or using other forms of tobacco-related products (including vaping)

• Smoking history <10 pack years and no smoking in the past 3 months

• FEV1 > 80% of predicted and FEV1/FVC > lower limit of normal.

• Ability to sign consent

• BMI ≥ 30 kg/m2

• Negative allergen skin test

Additional INCLUSION Criteria for MRI

• Outpatients of either gender, age > 18

• Willing and able to give informed consent and adhere to visit/protocol schedules. (Consent must be given before any study procedures are performed.)

• Women of childbearing potential must have a negative urine pregnancy test prior to MRI.

EXCLUSION Criteria

Asthma Cohort EXCLUSION:

• Respiratory tract infection within the 4 weeks prior to Visit 0

• Oral or systemic corticosteroid burst (for any indication) within the 4 weeks prior to Visit 0. One-time doses, such as intra-articular injections into a shoulder or knee joint, require a 4- week washout prior to Visit 0

• Asthma-related ER visit within the previous 4 weeks of Visit 0

• History of ICU admission/intubation due to asthma in the past 1 year

• Three or more asthma exacerbations requiring treatment with systemic corticosteroids in the past year consistent with severe asthma

• Asthma exacerbation requiring systemic corticosteroids within the 4 weeks prior to Visit 0

• Significant concomitant medical illness, including (but not limited to) heart disease, cancer, uncontrolled diabetes, other chronic lung diseases

• Chronic renal failure (creatinine > 2.0) at Visit 0

• Positive urine pregnancy test at Visit 0 or at any time during the study

• Untreated sleep apnea

• Participation in an intervention study (including, bronchoscopy) or use of investigative drugs within the past 30 days or plans to enroll in such a trial during the study

• Unable or unlikely to complete study assessments in the opinion of the Investigator

• Study intervention poses undue risk to patient in the opinion of the Investigator

• History of bronchial thermoplasty

Non-Asthma Cohort EXCLUSION:

• Respiratory tract infection within the 4 weeks prior to Visit 0 Oral or systemic corticosteroid burst (for any indication) within the 4 weeks prior to Visit 0. One-time doses, such as intra-articular injections into a shoulder or knee joint, require a 4-week washout prior to Visit 0

• Significant concomitant medical illness, including (but not limited to) heart disease, cancer, uncontrolled diabetes, other chronic lung diseases

• Chronic renal failure (creatinine > 2.0) at Visit 0

• Positive urine pregnancy test at Visit 0 or at any time during the study

• Untreated sleep apnea

• Participation in an intervention study (including bronchoscopy) or use of investigative drugs within the past 30 days or plans to enroll in such a trial during the study

• Unable or unlikely to complete study assessments in the opinion of the Investigator

• Study intervention poses undue risk to patient in the opinion of the Investigator

Additional EXCLUSION Criteria for MRI

• Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements

• Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine, shoulder circumference >140 cm*.) *This measurement is not an absolute as it can vary based on weight distribution.