HIV Clinical Trial
Official title:
Impact of Smoking and Its Cessation on Systemic and Airway Immune Activation
Verified date | January 2024 |
Source | Boston Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 53 |
Est. completion date | December 31, 2023 |
Est. primary completion date | December 31, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility | Inclusion criteria. 1. HIV infected on ART = 6 months 2. Virologically suppressed (<50 cop/ml) at the time of enrollment (lab test within 3 months ) 3. 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. 4. Laboratory values within 3 months prior to enrollment that meet the following criteria: 1. Hemoglobin = 8.0 g/dL 2. Platelet count = 80,000/mm3 5. 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 Exclusion criteria: 1. Pregnant or breast-feeding or less than 8 weeks post-partum. 2. Active malignancy and receiving concurrent treatment (i.e. chemotherapy, radiation therapy, investigational treatment). 3. Significant immunological illnesses/deficiencies 4. Recent active illness within the past 1 month (i.e. respiratory viral infection, pneumonia, bacterial infections, bone infection) 5. History of tuberculosis, lung cancer, bronchiectasis, pulmonary fibrosis, or pulmonary hypertension 6. 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. 7. 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.) 8. Spirometry criteria FEV1/FVC < 0.7 (definition of COPD) and GOLD (severe-very severe) Stage 3 or 4 within past 12 months 9. A history of alcohol dependence within the 6 months prior to enrollment 10. History of intolerance, sensitivity, allergy or anaphylaxis to lidocaine or other amide anesthetics, as well as benzocaine or other ester type anesthetics 11. History of recent myocardial infarction (within past 6 months). Non-coronary ischemia MI is allowed (i.e. cocaine-induced) 12. Chronic renal failure requiring dialysis 13. Decompensated cirrhosis 14. 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 15. 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 16. Recent abdominal surgery (within past 3 months) 17. Recent eye surgery (within past 3 months) 18. Investigator discretion |
Country | Name | City | State |
---|---|---|---|
United States | Boston Medical Center | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Boston Medical Center | National Institute on Drug Abuse (NIDA) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | .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 | 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-a, IFN-a/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). | Week 12 | |
Secondary | 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). | Week 12 | |
Secondary | 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. | Week 12 | |
Secondary | 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. | Week 12 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06162897 -
Case Management Dyad
|
N/A | |
Completed |
NCT03999411 -
Smartphone Intervention for Smoking Cessation and Improving Adherence to Treatment Among HIV Patients
|
Phase 4 | |
Completed |
NCT02528773 -
Efficacy of ART to Interrupt HIV Transmission Networks
|
||
Active, not recruiting |
NCT05454839 -
Preferences for Services in a Patient's First Six Months on Antiretroviral Therapy for HIV in South Africa
|
||
Recruiting |
NCT05322629 -
Stepped Care to Optimize PrEP Effectiveness in Pregnant and Postpartum Women
|
N/A | |
Completed |
NCT02579135 -
Reducing HIV Risk Among Adolescents: Evaluating Project HEART
|
N/A | |
Active, not recruiting |
NCT01790373 -
Evaluating a Youth-Focused Economic Empowerment Approach to HIV Treatment Adherence
|
N/A | |
Not yet recruiting |
NCT06044792 -
The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH
|
||
Completed |
NCT04039217 -
Antiretroviral Therapy (ART) Persistence in Different Body Compartments in HIV Negative MSM
|
Phase 4 | |
Active, not recruiting |
NCT04519970 -
Clinical Opportunities and Management to Exploit Biktarvy as Asynchronous Connection Key (COMEBACK)
|
N/A | |
Completed |
NCT04124536 -
Combination Partner HIV Testing Strategies for HIV-positive and HIV-negative Pregnant Women
|
N/A | |
Recruiting |
NCT05599581 -
Tu'Washindi RCT: Adolescent Girls in Kenya Taking Control of Their Health
|
N/A | |
Active, not recruiting |
NCT04588883 -
Strengthening Families Living With HIV in Kenya
|
N/A | |
Completed |
NCT02758093 -
Speed of Processing Training in Adults With HIV
|
N/A | |
Completed |
NCT02500446 -
Dolutegravir Impact on Residual Replication
|
Phase 4 | |
Completed |
NCT03805451 -
Life Steps for PrEP for Youth
|
N/A | |
Active, not recruiting |
NCT03902431 -
Translating the ABCS Into HIV Care
|
N/A | |
Completed |
NCT00729391 -
Women-Focused HIV Prevention in the Western Cape
|
Phase 2/Phase 3 | |
Recruiting |
NCT05736588 -
Elimisha HPV (Human Papillomavirus)
|
N/A | |
Recruiting |
NCT03589040 -
Darunavir and Rilpivirine Interactions With Etonogestrel Contraceptive Implant
|
Phase 2 |