Impact of Smoking and Its Cessation on Systemic and Airway Immune Activation

NCT02836067 | Completed DMC

• 2 other identifiers: H-35295R01DA042685-02
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV; Smoking

Outcome Measures

Primary Outcomes (1)

• .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).

  Week 12

Secondary Outcomes (4)

• Difference in levels of plasma inflammatory markers

  Week 12

• Differences in level of oxidative stress

  Week 12

• Differences in the level of measure of HIV residual viremia

  Week 12

• Differences airway transcriptional profile

  Week 12

Study Arms (2)

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

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

Procedure: Bronchoscopy; Procedure: Blood Draw; Behavioral: Questionnaires

Interventions

Counseling BEHAVIORAL

Smoking cessation counseling

Smokers

Smoking Cessation drugs OTHER

Medication to aid smoking cessation

Smokers

Bronchoscopy PROCEDURE

Bronchoscopy

Non-Smokers; Smokers

Blood Draw PROCEDURE

Screening and research blood draws

Non-Smokers; Smokers

Questionnaires BEHAVIORAL

Behavioral questionnaires

Non-Smokers; Smokers

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Boston Medical Center: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

Smoking

Interventions

Counseling; Bronchoscopy; Blood Specimen Collection; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Mental Health Services; Behavioral Disciplines and Activities; Community Health Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures; Specimen Handling; Clinical Laboratory Techniques; Punctures; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Archana Asundi, M.D.

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: July 18, 2016
• Study Start: June 15, 2017
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)