TGF-(Beta) and Susceptibility to RSV
| Status: | Recruiting |
|---|---|
| Conditions: | Asthma, Other Indications, Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases, Other |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 2/6/2019 |
| Start Date: | March 19, 2012 |
| Contact: | Lisa B Barber, MEd |
| Email: | lisa.barber@nih.gov |
| Phone: | (984) 287-4410 |
The Role of TGF-Beta in Asthmatic Epithelial Cell Susceptibility to RSV Infection
Background:
- Human respiratory syncytial virus (RSV) is a virus that causes respiratory tract
infections, and is frequently responsible for hospital visits in infants and children.
It can also trigger severe breathing problems for individuals who have asthma, but these
infections are generally better tolerated in non-asthmatics. Some research suggests that
lack of an efficient immune system response in people with asthma may make it difficult
for the body to fight the effects of RSV.
- Transforming Growth Factor-beta (TGF-[beta]) is a chemical in the body that is more
prevalent in the lungs of people with asthma and related respiratory disorders. More
information is needed about the effects of TGF-[beta] and whether it makes individuals
with asthma more prone to developing RSV. Researchers hope to use this information to
determine possible treatments and therapies for individuals with asthma who contract
RSV.
Objectives:
- To determine the possible role of TGF-[beta] in increased asthmatic susceptibility to RSV
infection.
Eligibility:
- Individuals between 18 and 60 years of age who are either healthy nonsmokers or mild
asthmatics.
Design:
- This study involves a screening visit and a study visit.
- Participants will be screened with a medical history and physical examination, as well
as blood samples and a pulmonary function test.
- At the study visit, participants will receive mild anesthetic and have a bronchoscopy,
in which researchers insert a bronchoscope through the participant s nose or mouth and
into the lungs to examine the lungs and collect lung cells.
- Participants will be contacted by a research team member 24 36 hours after the
bronchoscopy to ask about any side effects from the procedure.
- Human respiratory syncytial virus (RSV) is a virus that causes respiratory tract
infections, and is frequently responsible for hospital visits in infants and children.
It can also trigger severe breathing problems for individuals who have asthma, but these
infections are generally better tolerated in non-asthmatics. Some research suggests that
lack of an efficient immune system response in people with asthma may make it difficult
for the body to fight the effects of RSV.
- Transforming Growth Factor-beta (TGF-[beta]) is a chemical in the body that is more
prevalent in the lungs of people with asthma and related respiratory disorders. More
information is needed about the effects of TGF-[beta] and whether it makes individuals
with asthma more prone to developing RSV. Researchers hope to use this information to
determine possible treatments and therapies for individuals with asthma who contract
RSV.
Objectives:
- To determine the possible role of TGF-[beta] in increased asthmatic susceptibility to RSV
infection.
Eligibility:
- Individuals between 18 and 60 years of age who are either healthy nonsmokers or mild
asthmatics.
Design:
- This study involves a screening visit and a study visit.
- Participants will be screened with a medical history and physical examination, as well
as blood samples and a pulmonary function test.
- At the study visit, participants will receive mild anesthetic and have a bronchoscopy,
in which researchers insert a bronchoscope through the participant s nose or mouth and
into the lungs to examine the lungs and collect lung cells.
- Participants will be contacted by a research team member 24 36 hours after the
bronchoscopy to ask about any side effects from the procedure.
This is a cross-sectional, controlled study designed to investigate whether Transforming
Growth Factor-beta (TGF-beta) mediates increased asthmatic epithelial susceptibility to
respiratory syncytial virus (RSV) infection by examining responses to RSV infection in
epithelial cells cultured from asthmatic and non-asthmatic participants. Non-smoking healthy
adults and mild asthmatics, aged 18-60 years old, will be recruited to participate. Potential
participants will be prescreened and scheduled for a final eligibility visit that will
include medical history review, vital signs, physical examination, blood draw, and pulmonary
function tests (PFTs). After eligibility is confirmed, the participant will be scheduled for
bronchoscopy. During the bronchoscopy, bronchial epithelia and alveolar macrophages will be
obtained from the participant for analysis. Alveolar macrophages will be evaluated ex-vivo
for inflammatory activity at baseline and after stimulation.
The primary objective of the laboratory analysis is to determine if TGF-beta mediates
increased asthmatic epithelial susceptibility to RSV infection. The study has three aims
which are interrelated: 1) To determine if asthmatic bronchial epithelia express more
TGF-beta than normal epithelia; 2) to determine if RSV replication is greater in asthmatic
epithelia than normal epithelia; and 3) to determine if TGF-beta mediates asthmatic bronchial
epithelial susceptibility to RSV infections.
Growth Factor-beta (TGF-beta) mediates increased asthmatic epithelial susceptibility to
respiratory syncytial virus (RSV) infection by examining responses to RSV infection in
epithelial cells cultured from asthmatic and non-asthmatic participants. Non-smoking healthy
adults and mild asthmatics, aged 18-60 years old, will be recruited to participate. Potential
participants will be prescreened and scheduled for a final eligibility visit that will
include medical history review, vital signs, physical examination, blood draw, and pulmonary
function tests (PFTs). After eligibility is confirmed, the participant will be scheduled for
bronchoscopy. During the bronchoscopy, bronchial epithelia and alveolar macrophages will be
obtained from the participant for analysis. Alveolar macrophages will be evaluated ex-vivo
for inflammatory activity at baseline and after stimulation.
The primary objective of the laboratory analysis is to determine if TGF-beta mediates
increased asthmatic epithelial susceptibility to RSV infection. The study has three aims
which are interrelated: 1) To determine if asthmatic bronchial epithelia express more
TGF-beta than normal epithelia; 2) to determine if RSV replication is greater in asthmatic
epithelia than normal epithelia; and 3) to determine if TGF-beta mediates asthmatic bronchial
epithelial susceptibility to RSV infections.
-INCLUSION CRITERIA:
1. Male or female between 18 and 60 years of age
2. Non-asthmatics and mild asthmatics as defined below:
- Non-asthmatic must have no prior diagnosis of asthma, no history of health care
utilization or medication use for asthma, no current symptoms, and Forced
Expiratory Volume in 1 Second (FEV1) greater than or equal to 80% predicted.
- Asthmatics must have physician-diagnosed asthma for at least one year and
evidence of mild, persistent disease during the month prior to Visit 1 (based on
2008 GINA guidelines).
a) Participants who are currently taking a controller medication must:
i. use the equivalent to GINA Step 1 or 2 therapy; and
ii. have controlled disease, as defined by:
- daytime symptoms less than or equal to 2 times week, such as wheezing, tightness
in the chest, shortness of breath, and cough,
- no nocturnal symptoms;
b) Participants who are not currently taking a controller must have:
i.
tightness in the chest, shortness of breath, and cough;
ii. nocturnal awakenings > 2 times a month but < 1 time a week;
c) All asthmatic participants must have either:
i.
methacholine challenge (PC20 less than or equal to 4 mg / ml); or
ii.
equal to 80% with significant bronchodilator reversibility (at least 12% or 200ml
change in FEV1)
3. Participants must be able to understand and provide written informed consent
4. Participants must be able to travel to the CRU and the EPA
EXCLUSION CRITERIA:
1. Use of oral steroid treatment(s) within 30 days of Visit 1
2. Acute asthma-related healthcare utilization within 30 days of Visit 1, such as ED
visits, systemic corticosteroids, and nebulizer treatment for asthma exacerbation
3. Known or suspected respiratory infections within 30 days of Visit 1, such as flu,
pneumonia, severe cold, tuberculosis, or bronchitis
4. Known or suspected viral infection within 30 days of Visit 1
5. History of chronic obstructive pulmonary disease other than asthma
6. History of immunological disease or current cancer
7. Uncontrolled cardiovascular disease such as angina, prior myocardial infarction,
stroke, and high cholesterol
8. Cardiac malformations
9. Pulmonary hypertension
10. Bleeding disorders
11. Facial deformity, major facial surgery
12. Currently pregnant or breast feeding
13. Current smoker, significant second-hand smoke exposure (defined by urine cotinine >
100 ng/ml at Visit 1 or Visit 2) or former smokers (defined by a history of smoking >
100 cigarettes)
14. Insulin dependent diabetes
15. Used any of the following medications within 30 days of Visit 1: oral corticosteroids,
systemic immunosuppressants or other immune-modifying drugs [e.g., Rituxan, Humira,
Enbrel, Azathioprine (Imuran), Cyclosporine (Neoral, Sandimmune, and SangCya),
cyclophosphamide, TNF antagonists], anticoagulants (clopidogrel, heparin, enoxaparin
and related drugs, coumadin), and sustained use (i.e. more than one dose per day for
more than two days) of non-steroidal anti-inflammatory drugs (aspirin, ibuprofen,
indomethacin) within seven days of bronchoscopy
16. Allergy or history of adverse reactions to methacholine or lidocaine
17. Severe asthma as defined by a history of intubation for unstable asthma
18. Any condition that, in the investigator's opinion, places the participant at undue
risk for complications (e.g. from PFTs, fiberoptic bronchoscopy, bronchalveolar lavage
and/or bronchial brushings)
19. Temperature > 37.6 C; blood pressure < 90/50 mm Hg or blood pressure >170/95 mm Hg;
pulse rate < 50 or > 100 beats/minute
20. Body weight < 50 kg (<110 lbs)
21. The following abnormal lab values (values obtained during clinical assessment):
- Platelet count < 100,000 per 10(9)/L
- White blood cells count < 3000 per 10(9)/L
- Hematocrit < 35% for both female and male
- Prothrombin Time (PT) / Abnormal International Normalized Ratio (INR) and partial
prothromboplastin time (PTT) based on reference laboratory established reference
ranges
- Serum creatinine > 1.4 mg/dL
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