Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04155684 |
| Other study ID # |
STUDY19060360 |
| Secondary ID |
R01HL038630-01 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2018 |
| Est. completion date |
October 1, 2022 |
Study information
| Verified date |
October 2022 |
| Source |
University of Pittsburgh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Despite the high burden of respiratory symptoms in the HIV+ population, causes of chronic
obstructive pulmonary disease (COPD) in individuals with HIV are poorly understood. Microbial
communities present in the lungs or gut could play an important role in COPD via their
ability to stimulate inflammation and oxidative stress and by the interactions of microbial
and host gene transcription. By exploring the impact of the structure and function of
microbial communities on the host in HIV-associated COPD, this project could lead to
discovery of novel therapeutics to treat and prevent COPD. Subjects will be 20 HIV+
individuals with COPD (FEV1/FVC <0.70 and FEV1 and DLco<80% predicted) and 20 HIV+
individuals with normal lung function (controls) and 10 HIV negative individuals recruited
from our ongoing cohorts. Controls will be matched to the individuals with COPD based on age,
gender, pack-years of smoking, ART use, HIV viral suppression, and history of illicit drug
use. Bronchoscopy will be performed on all subjects. The investigator will uncover mechanisms
that contribute to COPD in HIV+ individuals, which will lead to interventional therapies. For
example, the investigators evaluate the impact of bacteria on lung epithelial cell gene
expression and inflammation and test ability of anti-inflammatories to alter responses.
Identification of other key pathways or microbes could also lead to testing of pro-biotics,
post-biotics (bacterial metabolites), or therapy with bacteria genetically modified for
desired function or metabolites.
Description:
Day one:
Respiratory questionnaires:
The Modified Medical Research Council Dyspnea scale (MMRC) and the St. George's
Questionnaire(SGQT) will be administered. These are paper and pencil questionnaires that
inquire about respiratory symptoms, quality of life, and other lung related issues. This will
take approximately 20 minutes to complete.
Blood Sample collection:
The subject will be asked to provide a blood sample by venipuncture of approximately 110mls
(7.4 tablespoon) at this study visit. The purpose of this collection is to have blood
processed for serum, plasma, and PBMCS, and a portion stored for RNA to be used for future
use. A hemoglobin and carboxyhemoglobin will be done in order to calculate the DLCO only if
the participant requires repeat spirometry and DLCO testing. In addition, part of this blood
will be used to perform routine clinical blood tests to assure that it is safe to proceed
with the bronchoscopy test. (CBC/DIFF/PLT, LYTS, BUN, Creatinine, Glucose, PT/PTT) The
de-identified research samples will be processed and stored at -80C. Personal information
will not be provided to individual research subjects as Dr. Morris's laboratory is not CLIA
certified .
Oral Sample collection:
A one time collection of saliva and tongue scraping will be done at the first visit.
Saliva sample will consist of between 1-5 mL of saliva spit into a sterile collection vessel.
Tongue scraping will consist of gentle scraping of the dorsal tongue (not hard enough to
cause abrasion) using a blunt, sterile device designed for this purpose that will then be
collected in a sterile collection vessel.
Stool collection: The investigator will ask participants to provide a stool sample. They will
be instructed on how to collect a stool specimen at home. The investigator will give them
instructions and a kit that will provide all the supplies needed to collect the stool and
return with it on day 2 of this study.
Lung function testing: (performed if there is not a PFT available from the past 3 months) The
routine lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured with
the flow-volume loop recorder on a NDD Easy One Pro testing system before and after
bronchodilator administration. The system is calibrated for body temperature and pressure of
saturated gas and volumes, per American Thoracic Society (ATS) standards . DLco will be
measured using the automated single-breath procedure of the integrated testing system, which
conforms with ATS standards. All testing will be reviewed by (PI). If any concerns or
abnormal results are discovered during this testing, a member of the research team will
notify the subject or the subject's primary care physician, who will assess the need to
provide additional evaluation.
Pregnancy Test: A urine pregnancy test will be performed on all women of child bearing
potential. Men and women who are post menopausal for at least 1 year or have been surgically
made sterile will not be included.
Day 2: (not necessarily consecutive days but within one week of day 1) Bronchoscopy: Fiber
optic bronchoscopy will be performed using the ATS recommendation and institutional protocols
for conscious sedation. The testing will be performed by a physician certified in pulmonary
medicine and proficient in the procedure and certified by UPMC. Fluoroscopy will not be used.
Subjects will be instructed to fast overnight and withhold aspirin and anti-inflammatory
analgesics for 48 hours prior to the procedure. Subjects will have undergone a pre-
bronchoscopy spirometry within the past 3 months and only clinically stable subjects
(FEV1>30% predicted after albuterol) will undergo the procedure. Subjects will also receive
Proventil HFA Inhaler 2 puffs, after 5 minutes will receive a second dose of Proventil 2
puffs prior to sending patient to the Bronchoscopy suite. Subjects may receive a drug to dry
secretions ( Atropine 0.6mg).
Subjects will receive a local anesthetic to the upper and lower airways and an intravenous
sedative and/or analgesic (midazolam; fentanyl). The midazolam dose will not exceed 10mg
and/or the fentanyl dose will not exceed 200 micrograms. Lidocaine will not exceed a dose of
9 mg/kg (0.9 cc of 1%/kg) or a maximum dose of 600 mg (60 cc 1%) during the procedure.
Subject monitoring will follow the local protocol for conscious/deep sedation. If needed,
subjects will receive additional short acting beta agonist. After transoral insertion of the
bronchoscope bronchoalveolar lavage will be performed. Blood pressure, heart rate, and oxygen
saturation will be monitored throughout the procedure. The physician may stop the procedure
at any time for clinical safety.
Bronchoalveolar lavage:
BAL will be performed with room temperature normal saline. After wedging the bronchoscope in
a (sub)segmental bronchus, approximately 50cc of saline will be instilled with each washing
and withdrawn by syringe aspiration. This will be repeated up to 4 times per segment as
needed. Amount of wash and selection of segments will be at the discretion of the physician.
Many clinical bronchoscopies are within this range of volume, and research bronchoscopies
have been found to be safe with volumes ranging from 100 to 300 cc even in subjects with
severe asthma (Wenzel S et al. Bronchoscopic evaluation of severe asthma. American Journal of
Respiratory and Critical Care Medicine 1997;156:737-43; Summary and recommendations of a
workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in
asthmatic patients. Chest 1985;88:136-38). The investigator will stop the lavage at any point
where the investigators do not feel that it would be clinically tolerated by the patient.
The volume collected after each withdrawal will be recorded.
Bronchial brushing:
Cytology bronchial brushing involves positioning the bronchoscope at the right middle or
lower lobe, passing a cytology brush through the bronchoscope and gently brushing the lining
of the airways. This may be repeated at least eight more times per segment to ensure an
adequate sample collection. If any sample collected is not acceptable or adequate for
analysis, another sample may be collected so long as the physician performing the
bronchoscopy procedure decides that no significant risk is present with the additional
collection.
1. Participant will be monitored at UPMC Montefiore until the sedation has worn off. After
the bronchoscopy is completed, the subject will wait in the bronchoscopy recovery area
or the clinical research CTRC to make sure thier breathing has not been affected by the
procedure and to be sure that the anesthesia has worn off. Pulse oximetry monitoring
will continue throughout recovery period. If the subject is not able to breathe as well
as they could before the bronchoscopy, the investigator will give additional albuterol
and check the breathing again.Participant will not be allowed to leave the recovery area
until their breathing is back to their normal level. If a participants breathing does
not return to baseline they will be required to be admitted overnight.
2. Participant will not be allowed to drive themselves home after the bronchoscopy.
Bronchoscopy pre and post sedation care will be conducted in the MUH CTRC. Staff are trained
research registered nurses and familiar with post bronchoscopy monitoring. Pulse oximetry
will be closely monitored and the subject will not be discharged until anesthesia has worn
off and the subject's breathing is back to normal.
The bronchoscopy procedure will take about 45 minutes, the participant will not be discharged
until anesthesia has worn off and their breathing is back to normal.
All bronchoscopies will be done in the pulmonary division bronchoscopy suite. Resuscitative
equipment and personnel are present in the room to minimize risk.
