HIVNCT02836067
Impact of Smoking and Its Cessation on Systemic and Airway Immune Activation
A study testing Counseling, Smoking Cessation drugs and Bronchoscopy in people with HIV and Smoking, run by Boston Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to learn how smoking affects the immune systems in people with HIV infection. The investigators would like to know if HIV infected smokers who quit smoking have different responses in their tissues from people who keep smoking. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- What is being tested?
- Counseling, Smoking Cessation drugs and Bronchoscopy
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2017to 31 Dec 2023
- Phase
- Interventional
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infected on ART ≥ 6 months
- Virologically suppressed (<50 cop/ml) at the time of enrollment (lab test within 3 months )
- Smoking Status:
- Currently Active Smoker: Self-reported regular cigarette use with positive cotinine test at screening visit.
- OR Non-smoker: self-reported non-smokers confirmed by negative cotinine test at screening visit.
- Laboratory values within 3 months prior to enrollment that meet the following criteria:
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- Hemoglobin ≥ 8.0 g/dL
- Platelet count ≥ 80,000/mm3
- For females of child-bearing potential: Negative urine pregnancy test (sensitive to 25 IU HCG) at screening visit.
- For purposes of this study, a female is considered of child-bearing potential unless:
- Permanently sterile (includes hysterectomy, bilateral oophorectomy, or bilateral salpingectomy)
- Medically documented ovarian failure
- Post-menopausal, defined as ≥ 55 years of age with cessation of menses for ≥ 12 months
Who cannot join
- Pregnant or breast-feeding or less than 8 weeks post-partum.
- Active malignancy and receiving concurrent treatment (i.e. chemotherapy, radiation therapy, investigational treatment).
- Significant immunological illnesses/deficiencies
- Recent active illness within the past 1 month (i.e. respiratory viral infection, pneumonia, bacterial infections, bone infection)
- History of tuberculosis, lung cancer, bronchiectasis, pulmonary fibrosis, or pulmonary hypertension
- Self-reported regular or recreational use of inhaled substances (such as marijuana, crack, fentanyl, heroin, hookah, e-cigarettes) as well as chewing tobacco within past month. Reports of no such use within the past month will be confirmed by a urine tox screen performed at the Screening Visit.
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- Self-reported regular use of inhaled substances (such as crack, fentanyl, heroin, hookah, e-cigarettes) in the past (prior to 1 month ago and within the past 5 years), with use occurring for > 1 year. (Marijuana use is allowable.)
- Spirometry criteria FEV1/FVC < 0.7 (definition of COPD) and GOLD (severe-very severe) Stage 3 or 4 within past 12 months
- A history of alcohol dependence within the 6 months prior to enrollment
- History of intolerance, sensitivity, allergy or anaphylaxis to lidocaine or other amide anesthetics, as well as benzocaine or other ester type anesthetics
- History of recent myocardial infarction (within past 6 months). Non-coronary ischemia MI is allowed (i.e. cocaine-induced)
- Chronic renal failure requiring dialysis
- Decompensated cirrhosis
- Currently taking anticoagulants including but not limited to: heparin (Hep-Lock, Hep-Pak), Hep-Pak CVC, Heparin Lock Flush), warfarin (Coumadin), tinzaparin (Innohep), enoxaparin (Lovenox), danaparoid (Orgaran), dalteparin (Fragmin), clopidogrel (Plavix), prophylactic aspirin, and NSAID use and unable to stop for 48 hours prior to bronchoscopy
- Taking any of the following medications within 30 days prior to enrollment: systemic steroids (inhaled or nasal steroid therapy is permitted), interleukins, systemic interferons (e.g., local injection of interferon alpha for treatment of HPV is permitted) or systemic chemotherapy, anti-TNF agents
- Recent abdominal surgery (within past 3 months)
- Recent eye surgery (within past 3 months)
- Investigator discretion
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to learn how smoking affects the immune systems in people with HIV infection. The investigators would like to know if HIV infected smokers who quit smoking have different responses in their tissues from people who keep smoking.
Read the detailed description
For Aim 1, a total of up to 30 patients with HIV disease who have never smoked will be recruited, with recruitment stopping before 30 samples if the samples from 20 patients that can be used in analysis have been obtained. These 20 non-smoker samples will be compared to those of 20 active smokers with HIV disease, without evidence of COPD from spirometry, who are matched in demographics. Smokers who are interested in participating in a smoking cessation program will be referred to our Clinical Trials Unit (CTU) for all subsequent study visits.
Additionally, a comparison group of 20 uninfected smokers who have already been enrolled in the co-investigator's (Dr. Kwon) study will be used as comparison group. These participants have similar inclusion/exclusion criteria as this study and have been verified to be HIV-antibody negative. The investigators will obtain de-identified samples and immunological and virological data already collected by Dr. Kwon. De-identified banked PBMC, plasma and BAL samples will also be accessible to us using a material transfer agreement to perform epithelial transcriptional gene expression profiling.
For Aim 2, a total of 100 HIV-infected individuals on effective ART who are active smokers and interested in participating in a smoking cessation program will be recruited. If 30 individuals who achieve 10-week of cessation are enrolled before 100 HIV smokers are fully enrolled, enrollment will cease, as 100 participants is an overestimate of the number of patients needed need to enroll to have 30 subjects achieve successful smoking cessation. Just like for nonsmokers, recruitment for both smoker cohorts will stop before 30 if samples from 20 patients that can be used in analysis have been obtained. The maximum total number of patients needed for the grant is 130 (100 HIV smokers, 30 HIV non-smokers).
About130 participants will be recruited from the BMC Center for Infectious Diseases (CID) outpatient clinic, other outpatient clinics within BMC, affiliated community health centers (CHCs), BWH, MGH, Tufts Medical Center, and Beth Israel Deaconess Medical Center. The BMC CID clinic serves the largest HIV-infected population in Boston, approximately 1,700 persons, and is composed largely of an urban socioeconomically disadvantaged population. Over 50% of HIV-infected patients in the CID are smokers, and >60% (based on prescription history of NRT, bupropion, varenicline) have attempted smoking cessation. Participants will be recruited from flyers, the BMC ReSPECT registry, medical record screening, and physician referrals.
- Being tested
- Counseling, Smoking Cessation drugs, Bronchoscopy, Blood Draw, Questionnaires
- Medical subject headings
- Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CounselingBehavioural
Smoking cessation counseling
Smoking Cessation drugsOther
Medication to aid smoking cessation
BronchoscopyProcedure or surgery
Bronchoscopy
Blood DrawProcedure or surgery
Screening and research blood draws
QuestionnairesBehavioural
Behavioral questionnaires
| Study group | Role | What they receive |
|---|---|---|
| Smokers | Other | HIV-positive smokers will be enrolled in a smoking cessation program including the following procedures:
Counseling Smoking cessation drugs Questionnaires Blood Draw Bronchoscopy Receives: Behavioral: Counseling; Other: Smoking Cessation drugs; Procedure: Bronchoscopy; Procedure: Blood Draw; Behavioral: Questionnaires |
| Non-Smokers | Other | HIV-positive non-smokers will be enrolled as a comparison group to HIV-positive smokers and will have the following procedures:
Questionnaires Blood Draw Bronchoscopy Receives: Procedure: Bronchoscopy; Procedure: Blood Draw; Behavioral: Questionnaires |
What is being measured
The primary outcome is the main question the study is designed to answer.
.Difference in T cell and monocyte immune subsets, level of activation
Aliquots of BAL and PBMC will be stained for surface antibodies to distinguish differentiation and activation markers. Monocyte cells will be phenotyped by CD3, CD19 and CD56 all on FITC, CD14 BUV 395, CD16 BV510, CCR2 PE, CX3CR1 APC, CD11c PEcf594, CD80 BV 421, CD86 BV 605, HLA-DR BV785, CD123 PE Cy7 and eFluor780 fixable viability dye. T cell populations will be stained for CD3, CD4, CD8, CD45RA, CCR7, CD27 and CD28; activation status by expression of CD25, CD38, CD69, HLA-DR, OX40. We will determine if they are Th2/Tc2-type cells by expression of CCR4, CCR8, T1/ST2, CRTH2. Flow will be performed on a LSRII (BD) and analyzed with FlowJo (Tree Star).
Measured: Week 12
Secondary outcomes (4)
Difference in levels of plasma inflammatory markers
For analysis of 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. sCD14 (R\&D) and iFABP (Hycult) will be measured by ELISA. LPS will be measured with the LAL assay (Pierce) and sCD163 (Trillium Diag). Additional human cytokines associated with inflammatory processes, including TNF-α, IFN-α/g, IL-6/7/10, IP-10 and MCP-1, will be measured using the Milliplex cytokine- kit (Millipore), read on a Luminex 100 and analyzed with Beadview software (Upstate Cell).
Measured: Week 12
Differences in level of oxidative stress
Cells from blood and BAL will be stimulated with and without PMA for 30 min. and incubated with DHR123 to directly detect intracellular ROS production. Cells will be stained with fluorescent antibodies recognizing lineage markers for T cells (CD3, CD4, CD8), macrophages (CD14), B cells (CD19, CD20), and granulocytes (CD66b).
Measured: Week 12
Differences in the level of measure of HIV residual viremia
Measure levels of HIV-1 ca-DNA, ca-RNA and 2-LTR circles in BAL and PBMC samples collected from HIV-infected smokers versus non-smokers. Cellular DNA and RNA from PBMCs and BAL cells will be extracted with AllPrep DNA/RNA mini kit (Qiagen). HIV-1 ca-DNA will be quantified using a sensitive quantitative PCR (qPCR) assay to measure a conserved LTR/gag region96, and modified in our lab118. Measurements of ca-DNA will be reported as copies of HIV DNA/106 cells. Quantification of a conserved region of the human CCR5 will be used to determine the number of cells in each sample well.
Measured: Week 12
Differences airway transcriptional profile
Compare gene expression profiles between HIV smokers and non-smokers. Library preparation for RNA sequencing will be accomplished using Illumina's TruSeq RNA Sample Prep Kit v2, using 200-500ng of total RNA from each bronchial epithelial brushing. Briefly, RNA will be isolated using poly(A) selection, fragmented into a range of lengths centered around 200 base pairs, and randomly primed for reverse transcription followed by first and second-strand synthesis to create double-stranded cDNA fragments. Subsequently, these fragments will undergo PCR amplification, purification, and be used for cluster generation on a cBot machine using Illumina TruSeq Paired-End Cluster Generation Kits.
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2016 (estimated)
- Study start15 Jun 2017
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Boston Medical CenterThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Archana Asundi, M.D., Principal investigator, Boston Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02836067
- Sponsor's protocol ID
- H-35295
- Other IDs
- R01DA042685-02
- Status last verified
- Jan 2024
- First submitted
- 14 Jul 2016
- Last updated
- 5 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Smoking and Its Cessation on Systemic and Airway Immune Activation
- ClinicalTrials.gov ID
- NCT02836067
- Acronym / sponsor ID
- H-35295
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Boston Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 15 Jun 2017 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 18 Jul 2016 (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 purpose of this study is to learn how smoking affects the immune systems in people with HIV infection. The investigators would like to know if HIV infected smokers who quit smoking have different responses in their tissues from people who keep smoking.
Detailed description
For Aim 1, a total of up to 30 patients with HIV disease who have never smoked will be recruited, with recruitment stopping before 30 samples if the samples from 20 patients that can be used in analysis have been obtained. These 20 non-smoker samples will be compared to those of 20 active smokers with HIV disease, without evidence of COPD from spirometry, who are matched in demographics. Smokers who are interested in participating in a smoking cessation program will be referred to our Clinical Trials Unit (CTU) for all subsequent study visits.
Additionally, a comparison group of 20 uninfected smokers who have already been enrolled in the co-investigator's (Dr. Kwon) study will be used as comparison group. These participants have similar inclusion/exclusion criteria as this study and have been verified to be HIV-antibody negative. The investigators will obtain de-identified samples and immunological and virological data already collected by Dr. Kwon. De-identified banked PBMC, plasma and BAL samples will also be accessible to us using a material transfer agreement to perform epithelial transcriptional gene expression profiling.
For Aim 2, a total of 100 HIV-infected individuals on effective ART who are active smokers and interested in participating in a smoking cessation program will be recruited. If 30 individuals who achieve 10-week of cessation are enrolled before 100 HIV smokers are fully enrolled, enrollment will cease, as 100 participants is an overestimate of the number of patients needed need to enroll to have 30 subjects achieve successful smoking cessation. Just like for nonsmokers, recruitment for both smoker cohorts will stop before 30 if samples from 20 patients that can be used in analysis have been obtained. The maximum total number of patients needed for the grant is 130 (100 HIV smokers, 30 HIV non-smokers).
About130 participants will be recruited from the BMC Center for Infectious Diseases (CID) outpatient clinic, other outpatient clinics within BMC, affiliated community health centers (CHCs), BWH, MGH, Tufts Medical Center, and Beth Israel Deaconess Medical Center. The BMC CID clinic serves the largest HIV-infected population in Boston, approximately 1,700 persons, and is composed largely of an urban socioeconomically disadvantaged population. Over 50% of HIV-infected patients in the CID are smokers, and >60% (based on prescription history of NRT, bupropion, varenicline) have attempted smoking cessation. Participants will be recruited from flyers, the BMC ReSPECT registry, medical record screening, and physician referrals.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Smokers | Other | Behavioral: Counseling, Other: Smoking Cessation drugs, Procedure: Bronchoscopy, Procedure: Blood Draw, Behavioral: QuestionnairesHIV-positive smokers will be enrolled in a smoking cessation program including the following procedures: Counseling Smoking cessation drugs Questionnaires Blood Draw Bronchoscopy |
| Non-Smokers | Other | Procedure: Bronchoscopy, Procedure: Blood Draw, Behavioral: QuestionnairesHIV-positive non-smokers will be enrolled as a comparison group to HIV-positive smokers and will have the following procedures: Questionnaires Blood Draw Bronchoscopy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- HIV infected on ART ≥ 6 months
- Virologically suppressed (<50 cop/ml) at the time of enrollment (lab test within 3 months )
- Smoking Status:
- Currently Active Smoker: Self-reported regular cigarette use with positive cotinine test at screening visit.
- OR Non-smoker: self-reported non-smokers confirmed by negative cotinine test at screening visit.
Key exclusion criteria (18 listed)
- Pregnant or breast-feeding or less than 8 weeks post-partum.
- Active malignancy and receiving concurrent treatment (i.e. chemotherapy, radiation therapy, investigational treatment).
- Significant immunological illnesses/deficiencies
- Recent active illness within the past 1 month (i.e. respiratory viral infection, pneumonia, bacterial infections, bone infection)
- History of tuberculosis, lung cancer, bronchiectasis, pulmonary fibrosis, or pulmonary hypertension
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 |
|---|---|---|
| CounselingSmoking cessation counseling | Behavioural | Smokers |
| Smoking Cessation drugsMedication to aid smoking cessation | Other | Smokers |
| BronchoscopyBronchoscopy | Procedure or surgery | Non-Smokers, Smokers |
| Blood DrawScreening and research blood draws | Procedure or surgery | Non-Smokers, Smokers |
| QuestionnairesBehavioral questionnaires | Behavioural | Non-Smokers, Smokers |
Primary outcome
.Difference in T cell and monocyte immune subsets, level of activation
Time frame: Week 12
Aliquots of BAL and PBMC will be stained for surface antibodies to distinguish differentiation and activation markers. Monocyte cells will be phenotyped by CD3, CD19 and CD56 all on FITC, CD14 BUV 395, CD16 BV510, CCR2 PE, CX3CR1 APC, CD11c PEcf594, CD80 BV 421, CD86 BV 605, HLA-DR BV785, CD123 PE Cy7 and eFluor780 fixable viability dye. T cell populations will be stained for CD3, CD4, CD8, CD45RA, CCR7, CD27 and CD28; activation status by expression of CD25, CD38, CD69, HLA-DR, OX40. We will determine if they are Th2/Tc2-type cells by expression of CCR4, CCR8, T1/ST2, CRTH2. Flow will be performed on a LSRII (BD) and analyzed with FlowJo (Tree Star).
4 secondary outcomes
Difference in levels of plasma inflammatory markers
Time frame: Week 12
Differences in level of oxidative stress
Time frame: Week 12
Differences in the level of measure of HIV residual viremia
Time frame: Week 12
Differences airway transcriptional profile
Time frame: Week 12
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 5 Jan 2024.
- 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.
Archana Asundi, M.D. principal investigator
Boston Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Counseling, Smoking Cessation drugs and Bronchoscopy in people with HIV and Smoking, run by Boston Medical Center 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 13 inclusion and 18 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 5 Jan 2024. 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?
.Difference in T cell and monocyte immune subsets, level of activation (time frame: Week 12). 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 5 Jan 2024.