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Microglia Activation in Asthma (MAIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04307667
Recruitment Status : Recruiting
First Posted : March 13, 2020
Last Update Posted : July 15, 2022
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:
The primary purpose of this study is to provide preliminary data to determine if an acute increase in airway inflammation, provoked by an inhaled allergen challenge, is associated with an increase in microglial activation and may inform whether individuals with asthma, in the long-term, are at increased risk for neurodegeneration, cognitive decline, and forms of dementia. Though in the long-term airway inflammation may be associated with neurodegenerative processes, these changes reflect the accumulation over a lifetime of allergen exposures and disease-related changes. This relationship between peripheral inflammation and microglial activation is analogous to the impact of sleep loss. No single night of poor sleep will lead to long-term change in brain structure, function, or cognitive function, but the accumulation of frequent and repeated sleep loss over a lifetime has been shown to have a major impact. These data will be used for a larger scale study to determine if asthma is a risk factor for neurodegeneration, and will inform brain health issues in asthma more broadly.

Condition or disease Intervention/treatment
Asthma Biological: Whole lung antigen challenge (WLAC) Radiation: [18F]FEPPA

Detailed Description:

First schedule version:

Screening Visit 0: Consent/Eligibility, Pregnancy Test, Vital Signs, Medical History, Concomitant Meds, Allergy Skin Test, Spirometry, Physical Exam, Blood Draw, MRI Simulation, Fraction of exhaled nitric oxide (FeNO)

Screening Visit 0a: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, WLAC, Fraction of exhaled nitric oxide (FeNO)

Visit 1: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Blood Draw, Sputum Induction, Fraction of exhaled nitric oxide (FeNO), Cognitive Tests, PET/MRI Scan, Questionnaires

Visit 2: Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Physical Exam, WLAC, Blood Draw, Fraction of exhaled nitric oxide (FeNO)

Visit 3: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Blood Draw, Sputum Induction, Fraction of exhaled nitric oxide (FeNO), Cognitive Tests, PET/MRI Scan, Questionnaires

Visit 4: Adverse Events, Spirometry, Fraction of exhaled nitric oxide (FeNO)

Second schedule version:

Screening Visit 0: Consent/Eligibility, Pregnancy Test, Vital Signs, Medical History, Concomitant Meds, Allergy Skin Test, Spirometry, Physical Exam, Blood Draw, MRI Simulation

Screening Visit 0a: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, WLAC

Visit 1: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Blood Draw, Sputum Induction, Fraction of exhaled nitric oxide (FeNO), Cognitive Tests, PET/MRI Scan, Questionnaires

Visit 2: Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Physical Exam, WLAC, Blood Draw, Fraction of exhaled nitric oxide (FeNO), Cognitive Tests, PET/MRI Scan, Questionnaires

Visit 3: Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Blood Draw, Sputum Induction, Fraction of exhaled nitric oxide (FeNO)

Visit 4: Adverse Events, Spirometry, Fraction of exhaled nitric oxide (FeNO)

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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Microglia Activation in Asthma
Actual Study Start Date : December 17, 2019
Estimated Primary Completion Date : December 1, 2023
Estimated Study Completion Date : December 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma


Intervention Details:
  • Biological: Whole lung antigen challenge (WLAC)
    Whole lung antigen challenge with cat hair, house dust mite, short ragweed or cat hair allergen extracts.
  • Radiation: [18F]FEPPA
    [18F]FEPPA is a radiotracer selective for translocator protein (TSPO) binding, which is elevated in activated microglia.


Primary Outcome Measures :
  1. Presence of Neuroinflammation measured by TSPO observed via PET scan [ Time Frame: up to 9 days ]
    The investigators propose that, in subjects with asthma, provocation of airway inflammation activates microglia, indicative of a neuroinflammatory signal. The hypothesis is that microglial activation will occur following an inhaled allergen challenge, relative to pre-challenge. Activation of microglia will be measured using positron emission tomography (PET) with the radiotracer [18F]FEPPA, a tracer selective for translocator protein (TSPO) binding, which is elevated in activated microglia.


Secondary Outcome Measures :
  1. Intensity of Airway Response measured by Fraction of exhaled nitric oxide (FeNO) Level [ Time Frame: up to 11 days ]
    The investigators propose that a more intense airway inflammatory response, created by the inhaled allergen challenge, will be associated with a greater increase in microglial activation. The hypothesis is that the increase in markers of airway inflammation, such as FeNO will be positively associated with the increase in microglial activation. Exhaled nitric oxide level will be determined using the Niox VERO instrumentation to measure FeNO. The test requires the participant to exhale into the mouthpiece of the FeNO measuring instrument for approximately 10 seconds.

  2. Intensity of Airway Response measured by Sputum Eosinophil Count [ Time Frame: up to 10 days ]
    The investigators propose that a more intense airway inflammatory response, created by the inhaled allergen challenge, will be associated with a greater increase in microglial activation. The hypothesis is that the increase in markers of airway inflammation, such as sputum eosinophil count will be positively associated with the increase in microglial activation. Sputum induction is a relatively simple, repeatable, and non-invasive method to collect airway secretions and are a highly relevant biological sample to assess airway inflammation.


Other Outcome Measures:
  1. Functionality Measured by Statistical Significance of Co-variation between Cognitive Tasks or Self-Report Instruments and Microglial Activation [ Time Frame: up to 10 days ]
    The investigators propose that a greater increase in microglial activation will be associated with reduced performance on tasks that assess cognitive function and greater psychological symptoms. The hypothesis is that a greater post-allergen challenge increase in microglial activation will be associated with a decrement in performance, relative to baseline, on measures of memory, attention, or executive function and elevated reports of depressive and anxious symptoms. The instruments may include the State-Trait Anxiety Inventory, Beck Depression Inventory, Beck Anxiety Inventory, Penn State Worry Questionnaire, Perceived Stress Scale, Stress and Adversity Inventory, Childhood Trauma and Adversity, and Peak Flow Diary (a diary of asthma symptoms recorded daily).


Biospecimen Retention:   Samples With DNA
  • Blood
  • Urine
  • Sputum


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adults (age 18-50) with mild allergic asthma
Criteria

Inclusion Criteria:

  • Male or female with no health concerns that might affect the outcome of the study
  • 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)
  • At least a 20% decrease in forced expiratory volume (FEV1) during the immediate response following inhaled allergen challenge
  • FEV1 > 70% at baseline
  • Positive immediate skin test for allergies to ragweed, cat dander, or house dust mite (historical data documented within the last 5 years is acceptable)
  • Women of child-bearing potential (WCBP) must have a negative urine pregnancy test for human chorionic gonadotropin (hCG) at screening and within 48 hours of the inhaled allergen challenge(s) and the positron emission tomography (PET) scans. WCBP must agree to use a medically-acceptable form of birth control for the duration of the study (medically-acceptable birth control methods can include: abstinence, barrier methods, oral contraceptives, injection contraceptives or skin absorption contraceptives).
  • Asthma medications consisting of only inhaled beta-agonists taken as needed or leukotriene inhibitors
  • Ability to tolerate a simulated functional magnetic resonance imaging (fMRI) 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 principal investigator's (PI) discretion.

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
  • Not able to withhold medication(s) as outlined by the study
  • Use of psychotropic medication that might affect function of neurocircuitry implicated in the investigator's hypotheses at the discretion of the PI or Co-Investigator (Co-I)
  • Needle phobia or claustrophobia
  • Major health problems such as autoimmune disease, heart disease, uncontrolled hypertension or lung diseases other than asthma. The listed health problems are definitively exclusionary, but decisions regarding major health problems not listed will be based upon the judgment of the investigator.
  • Pre-existing chronic infectious disease
  • Use of inhaled corticosteroids or oral corticosteroids within 1 month of screening
  • Use of an investigational drug within 30 days of entering the study. This criteria will be reviewed on a case by case basis by the principal investigators or co-investigator 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 WIMRs most current MRI screening form
  • Does not fit in the MRI scanner
  • 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
  • History of positive COVID-19 test (nasal swab or antibody test)
  • Have corrected vision and are not able to wear contacts or see sufficiently well to read without glasses or contacts, as glasses will not fit in the PET/MR head coil
  • Any other medical condition or disease that would impact subject safety or data integrity in the opinion of the PIs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04307667


Contacts
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Contact: Jane Sachs 6088902980 jfsachs@wisc.edu
Contact: Corrina Frye 6088903073 cfrye@wisc.edu

Locations
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United States, Wisconsin
University of Wisconsin Madison Recruiting
Madison, Wisconsin, United States, 53703-2637
Contact: Jane Sachs, MBE, MPH    680-890-2960    jfsachs@wisc.edu   
Principal Investigator: Melissa Rosenkranz, PhD         
Sponsors and Collaborators
University of Wisconsin, Madison
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Melissa Rosenkranz Center for Healthy Minds
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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT04307667    
Other Study ID Numbers: 2019-1309
A483000 ( Other Identifier: UW Madison )
L&S CTR FOR HEALTHY MINDS ( Other Identifier: UW Madison )
1R01HL123284-01A1 ( U.S. NIH Grant/Contract )
Protocol Version 4/21/2021 ( Other Identifier: UW Madison )
First Posted: March 13, 2020    Key Record Dates
Last Update Posted: July 15, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no specific sharing plan at this time except most likely will collaborate with researchers within and outside UW-Madison who would have access to data.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases