Got Doxy- 'Flipping the Script' on STI PEP

Not Applicable

Not yet recruiting

• Conditions: Sexually Transmitted Infections (STI)
• Interventions: Drug: Doxycycline monohydrate 200 mg; Other: Observation

• Registration Number: NCT07215325
• Lead Sponsor: Emory University

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2025-10
• Study First Submitted: 2025-10-03
• Study First Submitted QC: 2025-10-03
• Last Update Submitted: 2025-10-03
• Study First Posted: 2025-10-10
• Last Update Posted: 2025-10-10
• Study Start: 2025-11-01
• Primary Completion: 2028-09
• Study Completion: 2028-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 200

Inclusion Criteria

• 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 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

Exclusion Criteria

• Severe/uncontrolled comorbidities that could influence immune outcomes (e.g., diabetes, hypertension, co-infections), as assessed by the investigator.

• History of 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:

  1. Aspirin
  2. Warfarin, heparin (LMW or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
  3. Any form of rectally administered agent besides products (lubricants or douching) used for sexual intercourse
  4. NSAIDS within 72 hours of rectal sampling procedures

• Continued need for, or use during the 90 days before enrollment, of the following medications:

  1. Systemic immunomodulatory agents
  2. 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.)
  3. Use of experimental medications, vaccines, or biologicals in the 12 months before enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Doxycycline 200mg	Doxycycline monohydrate 200 mg	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.
Observation with biological sampling	Observation	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.

Primary Outcome Measures

Name	Time	Method
Composite inflammation score	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, TNF-α, MCP-1, IL-17A, IL-6, 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, TGF-β1) that was in the top quartile concentration for a maximum score of 9 and minimum score of -3.

Secondary Outcome Measures

Name	Time	Method
Tetracycline (TCN) Gene Abundance	Baseline and 12 weeks after the start of doxycycline administration	TCN gene-level abundance will be normalized using RPKG (reads per kilobase per genome equivalent), 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.
Estimated mass of antimicrobial resistance (AMR) Genes	Baseline and 12 weeks after the start of doxycycline administration	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.

Trial Locations

Locations (2)

Grady Health System (non-CRN); 🇺🇸 Atlanta, Georgia, United States

Hope Clinic; 🇺🇸 Atlanta, Georgia, United States