Hypersensitivity PneumonitisNCT03873649
Immune Response in Hypersensitivity Pneumonitis
An observational study of Hypersensitivity Pneumonitis, run by Nabeel Hamzeh at 1 site in United States.
Trial summary
Hypersensitivity pneumonitis (HP) is an inflammatory lung disease that is caused by exposure of susceptible individuals to organic materials in the environment. It is also known by various names depending on the exposure and some of these names include farmer's lung, pigeon breeder's lung, hot tub lung to name a few. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypersensitivity Pneumonitis
- What is being tested?
- Bronchoscopy with lavage
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Nov 2018to 30 Mar 2022
- Phase
- Observational
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Hypersensitivity Pneumonitis patients with confirmed subacute and chronic HP based on compatible radiological and pathological findings will be eligible for recruitment
Who may be able to join
- Adult between the ages of 18 and 80 years old.
- Non-smoker or previous smoker quit >6months ago.
- Radiological findings compatible with sub-acute or chronic HP4.
- Histopathological findings compatible with sub-acute or chronic HP4.
- Able to understand the consent process and procedures involved in the study.
Who cannot join
- Unable to understand the consent process or procedures involved in the study.
- End-stage lung disease defined as predominantly honeycombing on chest CT and/or FVC<60% and/or DLCO <30%.
- Requiring high oxygen needs >4L.
- Pregnancy.
- Treated with a biological agent within the past 6 months.
- Suspicion of current infection or within the past 3 months.
- Bleeding disorder or on anti-coagulants other than aspirin.
- Any co-morbid condition that increases risk of bronchoscopy including but not limited to cardiac disease, uncontrolled hypertension, uncontrolled diabetes and/or morbid obesity.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CD4 T-cell Immunephenotype in Hypersensitivity Pneumonitis
Hypersensitivity pneumonitis (HP) is an inflammatory lung disease that is caused by exposure of susceptible individuals to organic materials in the environment. It is also known by various names depending on the exposure and some of these names include farmer's lung, pigeon breeder's lung, hot tub lung to name a few. HP can cause lung scarring that impairs breathing and oxygenation. Early detection and avoidance of triggers can stop and reverse the disease but a significant number of patients continue to have active disease requiring treatment in spite of avoiding the trigger. The current choice of therapies is based on clinical experience and not on rigorous clinical trials. Not fully understanding the type of inflammation that is seen in HP and the cells involved in this inflammatory response limits health care providers' ability to choose drugs to study in HP that can stop the inflammation and limit scar formation. The goal of the investigators' study is to better understand the type of cells that are involved in the inflammatory response in the lungs of HP patients and what drives these cells to be active. By better understanding the type of cells and what drives them, health care providers can begin to choose and study drugs that can limit the inflammation and subsequent scarring. The investigators' will recruit HP patients and with their consent perform a scope of the lungs (bronchoscopy) with a limited lung wash to get the inflamed cells out of the lungs to further study them in the lab. The investigators' study will provide us with preliminary results to guide us in performing a more detailed study in the future to better understand the disease.
Read the detailed description
Hypersensitivity pneumonitis (HP) is a granulomatous lung disorder triggered by exposure to one of a multitude of organic antigens. Incidence rates of HP vary by geography, season and population studied but it is estimated to be the third most common interstitial lung disease with an estimated prevalence rate in the USA of 420-3000/100,0002. HP accounts for at least 7.5% of ILD related lung transplant. Exposure to an antigen in a susceptible host induces an inflammatory response with the subsequent formation of poorly formed granulomas that impact gas exchange which clinically manifests as shortness of breath, hypoxia and radiographic changes. HP can present acutely, subacutely or chronically depending on the duration of symptoms and radiographic changes. Radiographic manifestations of HP include ground-glass changes, centrilobular nodules, air trapping known as mosaic pattern, fibrosis, emphysema, or more frequently a combination of these. The cornerstone of management is identification and avoidance of the inciting agent which is effective if accomplished early in the disease process.
Although detection and avoidance of possible triggers can attenuate or reverse the disease, a significant number of patients continue to have active and/or progressive disease requiring chronic immunosuppressive therapy. Standard of care for IS therapy is corticosteroids and azathioprine but this is based on clinical experience and not based on randomized clinical trials(ref). The efficacy of this regimen is not known and patients develop persistent or progressive disease in spite of aggressive therapy leading to end stage lung disease necessitating lung transplantation or ending with death. To date, there are no randomized trials for immunosuppressive therapies and no reports of the use of biological agents in HP. The lack of studies is partially due to the lack of a thorough understanding of the immune response in HP especially in patient based studies that focus at the site of disease activity, the lungs.
The immunological response and pathways leading to this response have not been fully investigated especially in humans. The Th17 pathway has been implicated in disease pathogenesis and T-regulatory cell dysfunction has been described although studies in humans are limited. Recent work in sarcoidosis, a granulomatous lung disease, has shown that Th17.1 cells play a potential important role in granuloma immunopathogenesis. Through an R01 mechanism, the investigators are currently investigating the role of T-cell skewing and associated gene expression in sarcoidosis that is associated with progressive disease vs stable disease and the investigators are investigating its impact on disease course.
This gap in knowledge in HP has limited the choice and study of immunomodulatory agents in HP and especially biological agents in the treatment of persistent and progressive disease. To narrow this knowledge gap, the investigators propose conducting a study to investigate the lung CD4+ T-cell immunophenotype and CD4+ T-cell gene expression in HP to enhance the investigators' understanding of the immune response in HP and the pathways involved in the immune response which would enable the investigators to further pursue guided therapeutic trials in subacute and chronic HP.
- Conditions
- Hypersensitivity Pneumonitis
- Being tested
- Bronchoscopy with lavage
- Medical subject headings
- Alveolitis, Extrinsic Allergic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bronchoscopy with lavageOther
Also called blood draw
Bronchoscopy will be performed according to standard clinical procedures. Bronchoscopy will be performed under conscious sedation with continuous cardiopulmonary monitoring and the subject's upper airway will be anesthetized with topical lidocaine. The bronchoscope will be passed through the naris or mouth to the upper airway and then into the lower airway. 360cc of sterile saline will be instilled into 2 sub-segments by instilling and aspirating 3 aliquots of 60cc sequentially into each sub-segment.
Venipuncture to obtain peripheral blood mononuclear cells (PBMCs) for the proposed assays.
Cells collected will be analyzed for various T-cell subsets and gene expression to help determine the type of immune response.
| Study group | Role | What they receive |
|---|---|---|
| Patients with subacute or chronic hypersensitivity pneumonitis | Procedures that each subject will undergo include:
1. Chest CT scan to determine extent of disease.
2. Pulmonary function testing to determine severity of disease.
3. Bronchoscopy with lavage.
4. Venipuncture. Receives: Other: Bronchoscopy with lavage | |
| Healthy Controls | Inclusion:
1. Adult between the ages of 18 and 80 years old.
2. Non-smoker or previous smoker quit >6months ago.
3. Able to understand the consent process and procedures involved in the study.
Exclusion:
1. Unable to understand the consent process or procedures involved in the study.
2. Pregnancy.
3. Suspicion of current infection or within the past 3 months.
4. Bleeding disorder or on anti-coagulants other than aspirin.
5. Any co-morbid condition that increases risk of bronchoscopy including but not limited to cardiac disease, uncontrolled hypertension, uncontrolled diabetes and/or morbid obesity. Receives: Other: Bronchoscopy with lavage |
What is being measured
The primary outcome is the main question the study is designed to answer.
T-cell subtypes
T-cell subtypes will be determined by flow cytometry.
Measured: outcomes will be assessed after recruitment is complete in 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2019
- Study start29 Nov 2018
- Primary completion30 Jun 2021
- Study completion30 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypersensitivity PneumonitisStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nabeel Hamzeh
- Sponsor type
- University, hospital or other
- Collaborators
- National Jewish Health
- Responsible party
- Sponsor-investigator, Nabeel Hamzeh, University of Iowa
- Investigators
- Nabeel Hamzeh, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03873649
- Sponsor's protocol ID
- 201805937
- Status last verified
- May 2022
- First submitted
- 27 Feb 2019
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD4 T-cell Immunephenotype in Hypersensitivity Pneumonitis
- ClinicalTrials.gov ID
- NCT03873649
- Acronym / sponsor ID
- 201805937
- Conditions
- Hypersensitivity Pneumonitis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Nabeel HamzehUniversity, hospital or other
- Collaborators
- National Jewish Health
- Study start
- 29 Nov 2018 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Mar 2022 (actual)
- First posted
- 13 Mar 2019 (actual)
- 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.
Hypersensitivity pneumonitis (HP) is an inflammatory lung disease that is caused by exposure of susceptible individuals to organic materials in the environment. It is also known by various names depending on the exposure and some of these names include farmer's lung, pigeon breeder's lung, hot tub lung to name a few. HP can cause lung scarring that impairs breathing and oxygenation. Early detection and avoidance of triggers can stop and reverse the disease but a significant number of patients continue to have active disease requiring treatment in spite of avoiding the trigger. The current choice of therapies is based on clinical experience and not on rigorous clinical trials. Not fully understanding the type of inflammation that is seen in HP and the cells involved in this inflammatory response limits health care providers' ability to choose drugs to study in HP that can stop the inflammation and limit scar formation. The goal of the investigators' study is to better understand the type of cells that are involved in the inflammatory response in the lungs of HP patients and what drives these cells to be active. By better understanding the type of cells and what drives them, health care providers can begin to choose and study drugs that can limit the inflammation and subsequent scarring. The investigators' will recruit HP patients and with their consent perform a scope of the lungs (bronchoscopy) with a limited lung wash to get the inflamed cells out of the lungs to further study them in the lab. The investigators' study will provide us with preliminary results to guide us in performing a more detailed study in the future to better understand the disease.
Detailed description
Hypersensitivity pneumonitis (HP) is a granulomatous lung disorder triggered by exposure to one of a multitude of organic antigens. Incidence rates of HP vary by geography, season and population studied but it is estimated to be the third most common interstitial lung disease with an estimated prevalence rate in the USA of 420-3000/100,0002. HP accounts for at least 7.5% of ILD related lung transplant. Exposure to an antigen in a susceptible host induces an inflammatory response with the subsequent formation of poorly formed granulomas that impact gas exchange which clinically manifests as shortness of breath, hypoxia and radiographic changes. HP can present acutely, subacutely or chronically depending on the duration of symptoms and radiographic changes. Radiographic manifestations of HP include ground-glass changes, centrilobular nodules, air trapping known as mosaic pattern, fibrosis, emphysema, or more frequently a combination of these. The cornerstone of management is identification and avoidance of the inciting agent which is effective if accomplished early in the disease process.
Although detection and avoidance of possible triggers can attenuate or reverse the disease, a significant number of patients continue to have active and/or progressive disease requiring chronic immunosuppressive therapy. Standard of care for IS therapy is corticosteroids and azathioprine but this is based on clinical experience and not based on randomized clinical trials(ref). The efficacy of this regimen is not known and patients develop persistent or progressive disease in spite of aggressive therapy leading to end stage lung disease necessitating lung transplantation or ending with death. To date, there are no randomized trials for immunosuppressive therapies and no reports of the use of biological agents in HP. The lack of studies is partially due to the lack of a thorough understanding of the immune response in HP especially in patient based studies that focus at the site of disease activity, the lungs.
The immunological response and pathways leading to this response have not been fully investigated especially in humans. The Th17 pathway has been implicated in disease pathogenesis and T-regulatory cell dysfunction has been described although studies in humans are limited. Recent work in sarcoidosis, a granulomatous lung disease, has shown that Th17.1 cells play a potential important role in granuloma immunopathogenesis. Through an R01 mechanism, the investigators are currently investigating the role of T-cell skewing and associated gene expression in sarcoidosis that is associated with progressive disease vs stable disease and the investigators are investigating its impact on disease course.
This gap in knowledge in HP has limited the choice and study of immunomodulatory agents in HP and especially biological agents in the treatment of persistent and progressive disease. To narrow this knowledge gap, the investigators propose conducting a study to investigate the lung CD4+ T-cell immunophenotype and CD4+ T-cell gene expression in HP to enhance the investigators' understanding of the immune response in HP and the pathways involved in the immune response which would enable the investigators to further pursue guided therapeutic trials in subacute and chronic HP.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with subacute or chronic hypersensitivity pneumonitis | – | Other: Bronchoscopy with lavageProcedures that each subject will undergo include: 1. Chest CT scan to determine extent of disease. 2. Pulmonary function testing to determine severity of disease. 3. Bronchoscopy with lavage. 4. Venipuncture. |
| Healthy Controls | – | Other: Bronchoscopy with lavageInclusion: 1. Adult between the ages of 18 and 80 years old. 2. Non-smoker or previous smoker quit >6months ago. 3. Able to understand the consent process and procedures involved in the study. Exclusion: 1. Unable to understand the consent process or procedures involved in the study. 2. Pregnancy. 3. Suspicion of current infection or within the past 3 months. 4. Bleeding disorder or on anti-coagulants other than aspirin. 5. Any co-morbid condition that increases risk of bronchoscopy including but not limited to cardiac disease, uncontrolled hypertension, uncontrolled diabetes and/or morbid obesity. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Hypersensitivity Pneumonitis patients with confirmed subacute and chronic HP based on compatible radiological and pathological findings will be eligible for recruitment
Key inclusion criteria (5 listed)
- Adult between the ages of 18 and 80 years old.
- Non-smoker or previous smoker quit >6months ago.
- Radiological findings compatible with sub-acute or chronic HP4.
- Histopathological findings compatible with sub-acute or chronic HP4.
- Able to understand the consent process and procedures involved in the study.
Key exclusion criteria (8 listed)
- Unable to understand the consent process or procedures involved in the study.
- End-stage lung disease defined as predominantly honeycombing on chest CT and/or FVC<60% and/or DLCO <30%.
- Requiring high oxygen needs >4L.
- Pregnancy.
- Treated with a biological agent within the past 6 months.
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 with lavageAlso: blood drawBronchoscopy will be performed according to standard clinical procedures. Bronchoscopy will be performed under conscious sedation with continuous cardiopulmonary monitoring and the subject's upper airway will be anesthetized with topical lidocaine. The bronchoscope will be passed through the naris or mouth to the upper airway and then into the lower airway. 360cc of sterile saline will be instilled into 2 sub-segments by instilling and aspirating 3 aliquots of 60cc sequentially into each sub-segment. Venipuncture to obtain peripheral blood mononuclear cells (PBMCs) for the proposed assays. Cells collected will be analyzed for various T-cell subsets and gene expression to help determine the type of immune response. | Other | Healthy Controls, Patients with subacute or chronic hypersensitivity pneumonitis |
Primary outcome
T-cell subtypes
Time frame: outcomes will be assessed after recruitment is complete in 2 years.
T-cell subtypes will be determined by flow cytometry.
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 18 May 2022.
- Individual participant dataSharing planned: No
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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.
Nabeel Hamzeh, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypersensitivity Pneumonitis, run by Nabeel Hamzeh 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 5 inclusion and 8 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 18 May 2022. 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.
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?
T-cell subtypes (time frame: outcomes will be assessed after recruitment is complete in 2 years.). 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 18 May 2022.