- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03455959
Lung-Resident Memory Th2 Cells in Asthma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Rod A Rahimi, MD PhD
- Phone Number: 617-643-5482
- Email: rrahimi@mgh.harvard.edu
Study Contact Backup
- Name: Ben D Medoff
- Phone Number: (617) 726-6695
- Email: bmedoff@mgh.harvard.edu
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02116
- Recruiting
- Massachusetts General Hospital
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Contact:
- Rod A Rahimi, MD PhD
- Phone Number: 617-643-5482
- Email: rrahimi@mgh.harvard.edu
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Mild to moderate allergic asthma (AA) subjects
Inclusion Criteria:
- All subjects will have a baseline FEV1 no less than 75% of the predicted value.
All subjects will have a clinical history of allergic symptoms to an indoor allergen present in their home environment, either cat, dog or dust mite allergen, and confirmed skin reactivity (a positive allergen prick test) to the same allergen. The investigators will recruit both:
- subjects with mild intermittent or mild persistent asthma (consistent with NAEP Step 1 or Step 2 treatment options) who are not taking regular daily inhaled corticosteroids (ICS), and
- subjects with moderate persistent asthma (consistent with NAEP Step 3 treatment options) who are taking regular daily inhaled corticosteroids (ICS). In this subgroup, the maximum allowable daily ICS dose will be 220 MCG twice daily of fluticasone or equivalent ICS at screening.
- Life-long absence of cigarette smoking (lifetime total of < 5 pack-years and none in 5 years).
- Willing and able to give informed consent.
- Expressed the desire to participate in an interview with the principal investigator.
- Age between 18 and 55 years.
- All subjects will have a positive methacholine challenge with a PC20 < 16 mg/ml.
Exclusion Criteria:
- Women of childbearing potential who are pregnant (based on urine beta-HCG testing), are sexually active and not using contraception, are seeking to become pregnant or who are nursing.
- The presence of spontaneous asthmatic exacerbation or clinical evidence of upper respiratory tract infection within the previous 6 weeks and not requiring a change in daily inhaled corticosteroids (ICS) in the past 4 weeks.
- Participation in a research study involving a drug or biologic agent during the 30 days prior to the study.
- Intolerance to albuterol, atropine, lidocaine, fentanyl, or midazolam.
- Antihistamines within 7 days of the screening visit.
- Presence of diabetes mellitus, congestive heart failure, ventricular arrhythmias, history of a cerebrovascular accident, renal failure, history of anaphylaxis or cirrhosis.
- Use of systemic steroids, increased use of inhaled steroids, beta blockers and MAO inhibitors or a visit for an asthma exacerbation within 1 month of the screening visit.
- Antibiotic use for respiratory disease within 1 month of the characterization visit or a respiratory tract infection within 6 weeks of the bronchoscopy visits.
- A history of asthma-related respiratory failure requiring intubation.
- Taking beta-adrenergic blocking agents or monoamine oxidase inhibitors.
- Subjects with a high possibility of poor compliance with the study.
- No history of cigarette smoking within the past 5 years or > 5 pack years total.
- No indoor animal or second-hand cigarette smoke exposure. (It is also preferred but not required that dust mite allergic subjects have dust mite-proof encasings on their mattress and pillows.)
- Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection.
- Use of Xolair (omalizumab - anti-IgE monoclonal antibody) within 6 months.
- Immunotherapy with cat, dog, or dust mite extract now or in the past 10 years
- Use of other biologics for treatment of asthma or other medical condition, such as Nucala (mepolizumab, anti-IL-5 monoclonal antibody), Cinqair (reslizumab, anti-IL-5 monoclonal antibody), Fasenra (benralizumab, anti-IL-5 receptor monoclonal antibody), Dupixent (dupilumab, anti-IL-4 receptor-alpha monoclonal antibody), or other immunomodulatory biologics within 6 months.
Healthy Control (HC) Subjects HC subjects will be individuals who are in good overall health, age and sex matched to the asthmatic group, age 18 - 55 and nonallergic, i.e. entirely negative on a panel of prick skin tests that includes trees, grasses, weeds, cat, dog, dust mites, cockroach and molds, with no history of allergic rhinitis or asthma, no history of allergic symptoms caused by cats, dogs, or dust mite allergen exposure, life-long nonsmokers of cigarettes (defined as a lifetime total of < 5 packyears and none in 5 years), normal spirometry (i.e. FEV1 and FVC of at least 90% of predicted) and with a negative methacholine challenge test (PC20 of > 25 mg/ml).
Exclusion Criteria:
- A history of allergy, asthma, nasal or sinus disease.
- Exclusion criteria #1, 3-8 and 10-17 as indicated above for mild to moderate allergic asthma.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Allergic Asthmatic or Healthy Control Adults
Allergic Asthmatic or Healthy Control Adults will undergo Bronchoscopy/BAL and airway brushing
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Participants may receive 3 inhalations (90 ug ea) of albuterol to minimize bronchoconstriction.
Medication includes midazolam by intravenous injection, and fentanyl by intravenous injection as judged necessary.
2% lidocaine is delivered via atomizer spray to the oral pharynx for local anesthesia.
1% lidocaine is delivered through the bronchoscope to the vocal cords and lung segments for local anesthesia.
The bronchoscope is then passed through the vocal cords into the trachea.
Throughout the procedure, all participants will have continuous blood pressure, heart rate, and oxygen saturation monitoring.
Participants will be instructed to relate any discomfort or problems through a series of standardized hand signals.
Once in the lung, aliquots of sterile saline are instilled into two subsegments of the right middle lobe (preferred and if not possible then the right upper lobe) and withdrawn into a trap by gentle suction.
After completion of the BALs, endobronchial brushing of the airways will be performed using the airway brushings with a Conmed Harrell™ 4 mm unsheathed cytology brush.
Upon completing the brushing the investigators remove the bronchoscope with the brush in place to avoid shearing off isolated cells.
The brush will be gently glided back and forth on the airway epithelium 10 times in 2 different locations within the same airway.
The brush is then placed in media and flicked to remove the cells.
A second brush will then be introduced into an adjacent airway of the same lobe and gently glided back and forth on the airway epithelium 10 times in 2 different locations as was done with the first brush.
The second brush will also be placed in media and flicked to remove the cells.
There is some airway bleeding caused by the procedure, and participants are made aware that they may cough up small amounts of blood for 24-48 hours following the procedure.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The phenotype of Th2-Trm recovered from the airway mucosa
Time Frame: This is a single time point study with all information obtained at the time of bronchoscopy defined as Day 0.
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The investigators will determine the phenotype of Th2-Trm recovered from the airway mucosa of humans with asthma via flow cytometry to define the phenotype of human Th2-Trm.
The T cells will be recovered from airway bronchial brushing samples of patients with allergic asthma and allergy to an indoor allergen, and the investigators will obtain comparative samples from nonallergic healthy control subjects.
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This is a single time point study with all information obtained at the time of bronchoscopy defined as Day 0.
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The transcriptional profile of Th2-Trm recovered from the airway mucosa
Time Frame: This is a single time point study with all information obtained at the time of bronchoscopy defined as Day 0.
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The investigators will determine the transcriptional profile of Th2-Trm recovered from the airway mucosa of humans with asthma via single-cell RNA-seq analysis to define the phenotype of human Th2-Trm.
The T cells will be recovered from airway bronchial brushing samples of patients with allergic asthma and allergy to an indoor allergen, and the investigators will obtain comparative samples from nonallergic healthy control subjects.
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This is a single time point study with all information obtained at the time of bronchoscopy defined as Day 0.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Andrew D Luster, MGH
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2018P000117
- 2R01AI040618-21 (NIH)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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