The Effects of Doxycycline on Inflammation and the Microbiome: 'Flipping the Script' on STI PEP
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 4
- 主要终点
- Composite inflammation score
研究概览
简要总结
This study is being done to test the effects of doxycycline on inflammation and the bacteria in the body in people with HIV and in people on HIV pre-exposure prophylaxis. This drug is approved by the Food and Drug Administration (FDA) for the treatment of bacterial infections.
The study team will investigate whether the drug has additional effects on inflammation or on the bacteria that live in the body.
详细描述
This project aims to determine the potential anti-inflammatory and microbiome effects of doxycycline when used as post-exposure prophylaxis (Doxy PEP) for sexually transmitted infections (STIs).
This study is important in the field of research because it allows the investigators to define the systemic and gut anti-inflammatory, microbiome, and resistome effects of doxycycline when used as post-exposure prophylaxis (Doxy PEP) for sexually transmitted infections. The study population that this study seeks to enroll consists of healthy people assigned male at birth, with and without HIV, who are willing to undergo study procedures.
Study procedures will include the collection of medical history, as well as biological specimen sampling, such as blood and rectal tissue biopsies.
The duration of this clinical trial for study participants will be approximately 12 weeks. This will include five in-person visits lasting about 45 minutes to 1 hour (including two biopsy visits).
This study will utilize data specimen banking for future research.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age >18 years
- •Assigned male sex at birth
- •Good general health as assessed by a clinician at the screening study visit
- •For people with HIV, on suppressive antiretroviral therapy for at least 6 months with the most recent viral load documented <50 copies/ml and the most recent cluster of differentiation 4 (CD4)>300cells/ul
- •For people without HIV, taking oral daily, oral on-demand, or injectable pre-exposure prophylaxis for at least 3 months at the time of enrollment, with plans to continue for the duration of the study
- •Additional criteria apply
排除标准
- •Severe/uncontrolled comorbidities that could influence immune outcomes (e.g., diabetes, hypertension, co-infections), as assessed by the investigator.
- •History of inflammatory bowel disease (IBD) or other inflammatory, infiltrative, infectious, or vascular condition involving the lower GI tract that, in the judgment of the investigators, may be worsened by study procedures or may significantly distort the anatomy of the distal large bowel.
- •Known allergy to doxycycline
- •Use of any antibiotics within 3 months before screening
- •Significant lab abnormalities at baseline visit for rectal biopsies,
- •Continued need for the following medications during the study:
- •Warfarin, heparin (LMW or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
- •Any form of rectally administered agent besides products (lubricants or douching) used for sexual intercourse
- •NSAIDS within 72 hours of rectal sampling procedures
- •Continued need for, or use during the 90 days before enrollment, of the following medications:
- •Systemic immunomodulatory agents
- •Supraphysiologic doses of corticosteroids, except for short-course corticosteroids <7 days duration at the discretion of the investigator. (Gender affirming hormone therapy is not exclusionary.)
- •Use of experimental medications, vaccines, or biologicals in the 12 months before enrollment
研究组 & 干预措施
Observation with biological sampling
Males with HIV infection on antiretroviral therapy or without HIV infection on HIV pre-exposure prophylaxis who are not taking doxy-PEP will receive standard of care and will undergo biological sampling.
干预措施: Observation (Other)
Doxycycline 200mg
Males with HIV infection on antiretroviral therapy or without HIV infection on HIV pre-exposure prophylaxis who are not taking doxy-PEP will be enrolled and randomized to take 12 weeks of doxycycline 200 mg by mouth three times weekly.
Blood and rectal mucosal samples will be collected before the initiation of doxycycline.
干预措施: Doxycycline monohydrate 200 mg (Drug)
结局指标
主要结局
Composite inflammation score
时间窗: Baseline and 12 weeks after the start of doxycycline administration
A composite inflammation score in the blood and rectal secretions before and after doxy-PEP will be calculated for each participant: +1 point for each proinflammatory cytokine (IP-10, IL-1β, tumor necrosis factor (TNF-α), Monocyte chemoattractant protein-1 (MCP-1), IL-17A, IL-6, interferon (IFN-γ), IL-12p70, IL-8) that was in the top quartile concentration and -1 point for each anti-inflammatory cytokine (IL-4, IL-10), T-cell growth factor (TGF-β1) that was in the top quartile concentration for a maximum score of 9 and minimum score of -3.
Composite inflammation score
时间窗: Baseline and 12 weeks after the start of doxycycline administration
A composite inflammation score in the blood and rectal secretions before and after doxy-PEP will be calculated for each participant: +1 point for each proinflammatory cytokine (IP-10, IL-1β, tumor necrosis factor (TNF-α), Monocyte chemoattractant protein-1 (MCP-1), IL-17A, IL-6, interferon (IFN-γ), IL-12p70, IL-8) that was in the top quartile concentration and -1 point for each anti-inflammatory cytokine (IL-4, IL-10), T-cell growth factor (TGF-β1) that was in the top quartile concentration for a maximum score of 9 and minimum score of -3.
次要结局
- Tetracycline (TCN) Gene Abundance(Baseline and 12 weeks after the start of doxycycline administration)
- Estimated mass of antimicrobial resistance (AMR) Genes(Baseline and 12 weeks after the start of doxycycline administration)
- Tetracycline (TCN) Gene Abundance(Baseline and 12 weeks after the start of doxycycline administration)
- Estimated mass of antimicrobial resistance (AMR) Genes(Baseline and 12 weeks after the start of doxycycline administration)
研究者
Colleen Kelley
Professor of Medicine
Emory University