Got Doxy- 'Flipping the Script' on STI PEP
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexMale
Age18+
SponsorEmory University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Doxycycline monohydrate 200 mg
DrugDoxycycline monohydrate 200 mg (two 100 mg tablets) is used to treat or prevent infections that are strongly suspected to be caused by bacteria. Doxycycline monohydrate is an antimicrobial drug indicated for the treatment of bacterial infections, including sexually transmitted diseases. Centers for Disease Control and Prevention (CDC) recommends its use as post-exposure prophylaxis (PEP). Blood and rectal mucosal samples will be collected before doxycycline is initiated. Participants will be instructed to take 200 mg of doxycycline by mouth every Monday, Wednesday, and Friday. Additional doses of doxycycline will be permitted on other days if sex without a condom occurs per CDC guidance. After 12 weeks of at least three-weekly doxycycline, blood and rectal mucosal samples will be collected for immunologic and microbiome/resistome assays.
Observation
Other interventionStandard of care. Blood and rectal mucosal samples.
Treatment groups
200 Participants
are divided into 2 treatment groupsGroup A: Doxycycline 200mgExperimental treatment 1 intervention
Group B: Observation with biological samplingActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Composite inflammation score
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.
Time frame
Baseline and 12 weeks after the start of doxycycline administrationSecondary outcomes
1
Tetracycline (TCN) Gene Abundance
TCN gene-level abundance will be normalized using reads per kilobase per genome equivalent (RPKG), calculated from filtered contigs and estimated genome equivalents (MicrobeCensus). RPKG values will be summed by resistance class, sub-class (e.g., inactivation, target modification, efflux), and by host assignment (pathogen vs. commensal). Group differences in mean TCN RPKG values will be evaluated using non-parametric permutation tests.
Time frame
Baseline and 12 weeks after the start of doxycycline administration2
Estimated mass of antimicrobial resistance (AMR) Genes
To benchmark normalized abundance, the mass of AMR genes will be estimated using spike-in controls (ZymoBIOMICS). This will provide a quantitative measure of the total AMR gene burden per sample. Group differences in total AMR gene mass will be tested using non-parametric permutation tests.
Time frame
Baseline and 12 weeks after the start of doxycycline administrationSponsors and contacts
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Emory University
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
Source ClinicalTrials.gov