Comparison of Microglial Activation in Severe Asthma and Healthy Controls (MAIA-SC)

The goal of this clinical trial is to learn about how asthma influences brain function. The main questions it aims to answer are:

• How airway inflammation in asthma affects the brain; and,
• Whether airway inflammation in asthma is related to symptoms of depression and anxiety

Over the course of 3 visits, participants will:

• Complete questionnaires
• Complete computer tasks
• Undergo allergy skin test and breathing tests
• Give two blood samples
• Give a sputum sample
• Complete brain imaging scans

Researchers will compare results between participants with asthma, and participants who do not have asthma.

Study Overview

• Status: Recruiting
• Conditions: Asthma
• Intervention / Treatment: Combination product: PET/MRI using [18F]FEPPA tracer

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Rachel Kaspari; Phone Number: 608-265-6066; Email: rkaspari@medicine.wisc.edu
• Study Contact Backup: Name: Liana Larson; Phone Number: 608-263-0524; Email: llarson@medicine.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53703
      • Recruiting
      • Center for Healthy Minds
      • Principal Investigator: Melissa Rosenkranz, PhD
      • Contact: Janelle Grogan; Phone Number: 608-263-0524; Email: jegrogan@medicine.wisc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adults (age 18-75) with or without severe asthma.

Description

Inclusion Criteria:

• Ability to understand and the willingness to sign a written informed consent document
• Individuals with no health concerns that might affect the outcome of the study
• Age 18-75 years of age
• Ability to tolerate a simulated MRI brain scanning session
• In the opinion of the investigator, capable and willing to grant written informed consent and cooperate with study procedures and requirements
• High-affinity TSPO-binding genotype. Mixed (high/low) binding-affinity genotype may be included at PIs discretion
• For participants with severe asthma:
• Physician diagnosis of asthma for at least six months prior to screening (can be determined at the discretion of an asthma/allergy physician member of the study team)
• Severe asthmatics must meet the ATS definition of severe asthma and/or be currently receiving a GINA 5 therapy (or greater), which may include ongoing use of currently approved biologic immunomodulators

Exclusion Criteria:

• Current smoker (defined as more than 0.5 pack per week for the past 6 months and any smoking within two weeks of study procedures) or has a smoking history exceeding 5 pack years within the last 10 years
• Currently receiving immunotherapy
• Use of psychotropic medication that might affect function of neurocircuitry implicated in our hypotheses (at the discretion of the PI/Co-I)
• Inability to hold medications detailed in the medication hold schedule
• Needle phobia or claustrophobia
• Major health problems such as autoimmune disease, history of carotid stenosis, heart disease, uncontrolled hypertension, or lung diseases other than asthma, history of significant arrhythmias, and any of the following in the last 6 months: stroke/TIA, myocardial infarction, stent placement, or acute coronary syndrome. The listed health problems are definitively exclusionary, but decisions regarding major health problems not listed will be based upon the judgment of the investigator
• Use of biologic medication that might affect signaling pathways under investigation (at the discretion of the PI/Co-I)
• Pre-existing chronic infectious disease
• Scheduled use of non-selective beta-blockers prior to each study visit.
• Use of an investigational drug within 30 days of entering the study. This criterion will be reviewed on a case by case basis by the PI/Co-I to determine appropriate washout period. Appropriate wash out period may be greater than 30 days depending on the half-life of the investigational drug. Participants may be eligible for study participation after completing the washout period designated by the PI or Co-I (physician only).
• Any MRI incompatibility as determined by most current MRI screening form
• History of a diagnosed bipolar disorder, schizophrenia, or schizoaffective disorder
• History of serious head trauma or seizure disorder (can be included at the discretion of the PI or Co-I)
• Unable, in the judgement of the investigator, to comply with directions and/or tolerate the procedures required for participation in this study
• Pregnant or breast-feeding or has a planned pregnancy during the course of the study
• Any other medical condition or disease that would impact participant safety or data integrity in the opinion of the PI/CO-I

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants with asthma	Combination product: PET/MRI using [18F]FEPPA tracer; PET/MRI scans with [18F]FEPPA radiotracer selective for translocator protein (TSPO) binding, which is elevated in activated microglia
Participants without asthma	Combination product: PET/MRI using [18F]FEPPA tracer; PET/MRI scans with [18F]FEPPA radiotracer selective for translocator protein (TSPO) binding, which is elevated in activated microglia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Binding of [18F]-FEPPA	A whole-brain voxel-wise t-test will be performed in FMRIB Software Library (FSL) to identify regions where [18F]-FEPPA binding is significantly different between groups.	Up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
How activated microglia correspond to immune biomarkers in lung and blood	Whole-brain voxel-wise regressions in FSL will test the relationship between [18F]-FEPPA binding and cytokine levels	Up to 2 weeks
Relationship between activated microglia and cognitive function	whole-brain voxel-wise regressions in FSL will test the relationship between [18F]-FEPPA binding and cognitive function	Up to 2 weeks
Relationship between activated microglia and psychological symptoms	whole-brain voxel-wise regressions in FSL will test the relationship between [18F]-FEPPA binding and psychological symptoms	Up to 2 weeks

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Melissa Rosenkranz, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: February 29, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 2023-1626; A538900 (Other Identifier: UW Madison); SMPH/PSYCHIATRY/PSYCHIATRY (Other Identifier: UW Madison); 1RF1AG082215-01 (U.S. NIH Grant/Contract); Protocol Version 10/15/2023 (Other Identifier: UW- Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No