AsthmaPhase 1MGH-001NCT01612936
T Cell Effector and Regulatory Mechanisms in Asthma
A Phase 1 study testing Bronchoscopy, Segmental Allergen Challenge and Broncheoalveolar Lavage and PET-CT imaging(13NN perfusion/ventilation, 18FDG inflammation, and CT imaging) in people with Asthma and Allergies, run by Andrew D. Luster, M.D.,Ph.D. at 1 site in United States.
Trial summary
The specific hypothesis for this study is that there are fundamental differences in T effector and T regulatory cell responses in the lung to allergens in allergic asthma (AA) when compared to allergic nonasthmatics (ANA) that account for the difference in clinical responses. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- What is being tested?
- Bronchoscopy, Segmental Allergen Challenge and Broncheoalveolar Lavage and PET-CT imaging(13NN perfusion/ventilation, 18FDG inflammation, and CT imaging)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 168 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to Sep 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subjects with Allergic Asthma (AA subjects):
- All subjects will have a baseline FEV1 no less than 75 % of the predicted value after bronchodilator administration.
- All subjects will have both a clinical history of allergic symptoms to cat or dust mite allergen and a positive allergen prick test (3 mm diameter greater than diluent control)
- 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.
Show all 18Show fewer
- Age between 18 and 50 years.
- A methacholine PC20 < 16 mg/ml.
- Asthma of severity defined as: requiring no more than step 3 therapy (NHLBI Guidelines, 2007 EPR-3, http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf), well-controlled and having a validated asthma control test (ACT) score of > 19 for one month prior to the screening visit, and able to tolerate a 2 week stoppage of inhaled corticosteroids prior to Visit 2.
- Allergic Nonasthmatic Subjects (ANA subjects):
- ANA subjects will have a history of at least one of the following: (a) allergic rhinitis (with one or more of the following symptoms: nasal congestion, sneezing, runny nose, postnasal drainage), (b) allergic conjunctivitis (ocular itching, tearing and/or swelling) or (c) contact allergy associated with cat dander or dust mite and a positive allergy test to the same allergen.
- All subjects will have a baseline FEV1 and FVC determined at the characterization visit that is no less than 90 % of the predicted value before bronchodilator administration.
- All subjects will have a positive allergy skin prick test to cat dander or dust mite allergen.
- All subjects will be in good general health.
- 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 50 years.
Who cannot join
- Subjects with Allergic Asthma (AA subjects):
- Women of childbearing potential who are pregnant (based on urine beta-HCG or STAT quantitative serum hCG testing), are sexually active and not using contraception, are seeking to become pregnant, or who are nursing.
- The presence of spontaneous asthmatic episode or clinical evidence of upper respiratory tract infection within the previous 6 weeks.
- Participation in a research study involving a drug or biologic during the 30 days prior to the study.
- Intolerance to albuterol, atropine, lidocaine, fentanyl, or midazolam.
- Antihistamines within 7 days of the screening visit.
Show all 30Show fewer
- 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.
- Quantitative skin-prick test positive reaction down to an allergen concentration of 0.056 BAU or AU/ml.
- Subjects with a high possibility of poor compliance with the study.
- Have a history of cigarette smoking within the past 5 years or > 5 pack years total.
- Having second-hand cigarette smoke exposure or indoor furry pets except in the case of dog, if the subject is not allergic to the dog and the subject has a negative skin test to dog.
- Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection.
- Use of Xolair (omalizumab - anti-IgE monoclonal antibody) for 6 months.
- Immunotherapy with cat or dust mite extract now or in the past.
- Use of prophylactic aspirin for cardiovascular disease
- Non-English speakers
- Allergic Nonasthmatic Subjects (ANA subjects):
- A history of asthma.
- Exclusion criteria #1, 3-8 and 10- 18 from (AA) above.
- A methacholine PC20 < 16 mg/ml.
- Additional exclusion Criteria Specific to PET Imaging:
- Anyone unable to lay flat on the scanner table for imaging.
- We will exclude severely and morbidly obese subjects (BMI> 32) because of the poor quality of images that can be obtained and weight restrictions on the scanner.
- Those with a diffusing capacity < 80% predicted (if known),
- Subjects with known exposure to agents that are associated with pulmonary disease (i.e. asbestos, silica)
- Subjects who have had any research related radiation exposure greater than 15 mSv within the past year will be excluded.
- Individuals with known allergy or hypersensitivity to FDG will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
The specific hypothesis for this study is that there are fundamental differences in T effector and T regulatory cell responses in the lung to allergens in allergic asthma (AA) when compared to allergic nonasthmatics (ANA) that account for the difference in clinical responses. We will address this by comparing T cell responses in AA versus ANA subjects. These experiments will correlate T cell responses with measures of airway physiology using state-of-the art lung imaging and examine mechanisms controlling T cell activation in the airways of AA and the function of airway T regulatory cells during AA.
Read the detailed description
Despite advances in medications, allergic diseases, including allergic asthma, continue to rise in prevalence. For this reason, there is a need for a better understanding of the mechanisms of allergic diseases and novel insights into modulating allergic inflammation. CD4+ Th2-type lymphocytes seems to be central to the pathogenesis of allergic disease, as the levels of these cells and Th2 cytokines (IL-4, IL-5 and IL-13) are elevated in the airways of allergic asthma patients. The unifying hypothesis of this project is that understanding the mechanisms that determine the critical balance of effector and regulatory allergen-specific T cell activity in asthma will lead to new approaches for inducing allergen-specific tolerance and new therapeutic strategies for asthma.
- Being tested
- Bronchoscopy, Segmental Allergen Challenge and Broncheoalveolar Lavage, PET-CT imaging(13NN perfusion/ventilation, 18FDG inflammation, and CT imaging)
- Keywords
- Asthma, Allergic, Inflammation, Constriction, Airway, Challenge, Chemokines
- Medical subject headings
- Asthma, Hypersensitivity, Inflammation, Constriction, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bronchoscopy, Segmental Allergen Challenge and Broncheoalveolar LavageBiological
Also called One of 3 Standardized allergen extracts will be used:, 1)Cat hair, 2)Dust Mite Dermatophagoides farinae, 3)Dust Mite Dermatophagoides pteronyssinus
On the day of the first bronchoscopy,BAL will first be performed in the lingula without instillation of diluent or allergen.Then, a 2-ml aliquot of isotonic diluent is instilled into the right upper lobe. Then, the procedure will be repeated in the right middle lobe with instillation of 2-ml of standardized cat or mite allergen solution.A "test dose" concentration of allergen is administered first consisting of 2 ml of allergen at 1/10th(Cat,D.farinae) or 1/30th(D. pteronyssinus) the threshold concentration.If on visual inspection through the bronchoscope, there is no evidence of mucosal inflammation after two minutes, a second segmental allergen challenge will be done in the right middle lobe using 2-ml of full-dose allergen at the threshold concentration(Cat,D.farinae) or 1/3th the threshold concentration(D.pteronyssinus).This dose will be predetermined by quantitative skin prick testing.A second bronchoscopy is performed 24 hours after delivery of allergen extract and diluent.
PET-CT imaging(13NN perfusion/ventilation, 18FDG inflammation, and CT imaging)Procedure or surgery
Also called 13N-N2 saline, 18F-FDG, 0.019 mSv/MBq
Imaging is first performed the evening prior to the 1st bronchoscopy.An IV catheter is placed.An attenuation correction is performed to remove image distortion using a chest CT volumetric scan.Subjects are instructed to exhale to the same mean lung volume of the CT scan and hold their breath for 20sec.Simultaneous with apnea,13NNsaline is injected IV and a series of PET scans is acquired.Then subjects resume breathing, matching their previous respiratory rate and tidal volume.After 3 min,within an interval of 1 min,spirometry and 2 deep inhalations are performed,followed by 1 min of washout. For the second imaging visit, which will occur 24 hour later, the imaging sequence will be repeated as described above, but will also include 18FDG infusion.At least 30 minutes after the 13NN injection,10mCi of 18FDG is infused. Then, images are collected over a 75 minutes.Venous blood is sampled at 5 different time points over a 40-45 minute time window to determine plasma radioactive levels.
| Study group | Role | What they receive |
|---|---|---|
| Allergic asthmatic, allergic nonasthmatic | Experimental | Adults who are allergic asthmatics or allergic non-asthmatics will receive segmental allergen challenge to the lung Receives: Biological: Bronchoscopy, Segmental Allergen Challenge and Broncheoalveolar Lavage; Procedure: PET-CT imaging(13NN perfusion/ventilation, 18FDG inflammation, and CT imaging) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in airway physiology and airway constriction
The primary endpoints are differences in airway physiology and airway constriction following segmental allergen challenge (SAC) in AA and ANA subjects using positron emission tomography (PET) in combination with high-resolution computed tomography (HRCT)
Measured: 24 hours
Secondary outcomes (3)
Differences in BAL inflammatory mediator release
We will assess each BAL for inflammation and inflammatory mediator release. A pre-challenge BAL is obtained to insure the subject does not have baseline inflammation prior to the allergen challenge. The diluent challenged segment is used to control for effects of bronchoscopy and instillation of fluid in the lung. Analysis of the allergen challenged segment is done to confirm that allergen exposure led to airway inflammation, and allows us to correlate changes in airway physiology to inflammation in the allergen exposed segment.
Measured: 24 hours
Differences in cellular analysis of BAL
A differential is calculated for each sample by counting at least 200 cells using morphology and staining characteristics to separate them into macrophages, lymphocytes, eosinophils, and neutrophils, allowing us to calculate the number and percentage of each cell type in the BAL. The cells are also stained for a panel of cell surface markers and intracytoplasmic proteins and analyzed by flow cytometry. This analysis will allow us to ensure that each subject responded to allergen challenge response with appropriate eosinophil and T cell recruitment into the BAL.
Measured: 24 hours
Differences in BAL inflammatory protein levels
BAL fluid will be concentrated 10-fold using a Centricon filter (Millipore) with a 3,000 MW cutoff. We have found that assaying for cytokines is more reliable when the BAL is concentrated 10-fold since BAL is diluted ~100-fold by the procedure.Concentrations of a panel of 42 different cytokines, chemokines, and growth factors are measured using a LINCOplex human cytokine-chemokine kit as per manufacturer's guidelines (Millipore) and read on a Luminex 100 (Luminex Corporation). Results are analyzed using Beadview software (UpstateCell Signaling Solutions).
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2012 (estimated)
- Study startSep 2012
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andrew D. Luster, M.D.,Ph.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Andrew D. Luster, M.D.,Ph.D., Massachusetts General Hospital
- Investigators
- Andrew D Luster, M.D., Ph.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01612936
- Sponsor's protocol ID
- 2012P000705
- Other IDs
- 1U19AI095261
- Acronym
- MGH-001
- Status last verified
- Sep 2017
- First submitted
- 4 Jun 2012
- Last updated
- 15 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T Cell Effector and Regulatory Mechanisms in Asthma
- ClinicalTrials.gov ID
- NCT01612936
- Acronym / sponsor ID
- MGH-001 / 2012P000705
- Keywords
- Asthma, Allergic, Inflammation, Constriction, Airway, Challenge, Chemokines
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- Andrew D. Luster, M.D.,Ph.D.University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Sep 2012
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 6 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The specific hypothesis for this study is that there are fundamental differences in T effector and T regulatory cell responses in the lung to allergens in allergic asthma (AA) when compared to allergic nonasthmatics (ANA) that account for the difference in clinical responses. We will address this by comparing T cell responses in AA versus ANA subjects. These experiments will correlate T cell responses with measures of airway physiology using state-of-the art lung imaging and examine mechanisms controlling T cell activation in the airways of AA and the function of airway T regulatory cells during AA.
Detailed description
Despite advances in medications, allergic diseases, including allergic asthma, continue to rise in prevalence. For this reason, there is a need for a better understanding of the mechanisms of allergic diseases and novel insights into modulating allergic inflammation. CD4+ Th2-type lymphocytes seems to be central to the pathogenesis of allergic disease, as the levels of these cells and Th2 cytokines (IL-4, IL-5 and IL-13) are elevated in the airways of allergic asthma patients. The unifying hypothesis of this project is that understanding the mechanisms that determine the critical balance of effector and regulatory allergen-specific T cell activity in asthma will lead to new approaches for inducing allergen-specific tolerance and new therapeutic strategies for asthma.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allergic asthmatic, allergic nonasthmatic | Experimental | Biological: Bronchoscopy, Segmental Allergen Challenge and Broncheoalveolar Lavage, Procedure: PET-CT imaging(13NN perfusion/ventilation, 18FDG inflammation, and CT imaging)Adults who are allergic asthmatics or allergic non-asthmatics will receive segmental allergen challenge to the lung |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- All subjects will have a baseline FEV1 no less than 75 % of the predicted value after bronchodilator administration.
- All subjects will have both a clinical history of allergic symptoms to cat or dust mite allergen and a positive allergen prick test (3 mm diameter greater than diluent control)
- 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.
Key exclusion criteria (30 listed)
- Women of childbearing potential who are pregnant (based on urine beta-HCG or STAT quantitative serum hCG testing), are sexually active and not using contraception, are seeking to become pregnant, or who are nursing.
- The presence of spontaneous asthmatic episode or clinical evidence of upper respiratory tract infection within the previous 6 weeks.
- Participation in a research study involving a drug or biologic during the 30 days prior to the study.
- Intolerance to albuterol, atropine, lidocaine, fentanyl, or midazolam.
- Antihistamines within 7 days of the screening visit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bronchoscopy, Segmental Allergen Challenge and Broncheoalveolar LavageAlso: One of 3 Standardized allergen extracts will be used:, 1)Cat hair, 2)Dust Mite Dermatophagoides farinae, 3)Dust Mite Dermatophagoides pteronyssinusOn the day of the first bronchoscopy,BAL will first be performed in the lingula without instillation of diluent or allergen.Then, a 2-ml aliquot of isotonic diluent is instilled into the right upper lobe. Then, the procedure will be repeated in the right middle lobe with instillation of 2-ml of standardized cat or mite allergen solution.A "test dose" concentration of allergen is administered first consisting of 2 ml of allergen at 1/10th(Cat,D.farinae) or 1/30th(D. pteronyssinus) the threshold concentration.If on visual inspection through the bronchoscope, there is no evidence of mucosal inflammation after two minutes, a second segmental allergen challenge will be done in the right middle lobe using 2-ml of full-dose allergen at the threshold concentration(Cat,D.farinae) or 1/3th the threshold concentration(D.pteronyssinus).This dose will be predetermined by quantitative skin prick testing.A second bronchoscopy is performed 24 hours after delivery of allergen extract and diluent. | Biological | Allergic asthmatic, allergic nonasthmatic |
| PET-CT imaging(13NN perfusion/ventilation, 18FDG inflammation, and CT imaging)Also: 13N-N2 saline, 18F-FDG, 0.019 mSv/MBqImaging is first performed the evening prior to the 1st bronchoscopy.An IV catheter is placed.An attenuation correction is performed to remove image distortion using a chest CT volumetric scan.Subjects are instructed to exhale to the same mean lung volume of the CT scan and hold their breath for 20sec.Simultaneous with apnea,13NNsaline is injected IV and a series of PET scans is acquired.Then subjects resume breathing, matching their previous respiratory rate and tidal volume.After 3 min,within an interval of 1 min,spirometry and 2 deep inhalations are performed,followed by 1 min of washout. For the second imaging visit, which will occur 24 hour later, the imaging sequence will be repeated as described above, but will also include 18FDG infusion.At least 30 minutes after the 13NN injection,10mCi of 18FDG is infused. Then, images are collected over a 75 minutes.Venous blood is sampled at 5 different time points over a 40-45 minute time window to determine plasma radioactive levels. | Procedure or surgery | Allergic asthmatic, allergic nonasthmatic |
Primary outcome
Differences in airway physiology and airway constriction
Time frame: 24 hours
The primary endpoints are differences in airway physiology and airway constriction following segmental allergen challenge (SAC) in AA and ANA subjects using positron emission tomography (PET) in combination with high-resolution computed tomography (HRCT)
3 secondary outcomes
Differences in BAL inflammatory mediator release
Time frame: 24 hours
Differences in cellular analysis of BAL
Time frame: 24 hours
Differences in BAL inflammatory protein levels
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew D Luster, M.D., Ph.D. principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bronchoscopy, Segmental Allergen Challenge and Broncheoalveolar Lavage and PET-CT imaging(13NN perfusion/ventilation, 18FDG inflammation, and CT imaging) in people with Asthma and Allergies, run by Andrew D. Luster, M.D.,Ph.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in airway physiology and airway constriction (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2017.