Got Doxy- 'Flipping the Script' on STI PEP

NCT07215325 | Recruiting Phase 4 FDA Drug

• 3 other identifiers: STUDY000093551R01AI192319-012025P009920
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

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.

Conditions

Sexually Transmitted Infections (STI)

Keywords

Doxycycline post-exposure prophylaxis (doxy-PEP); Gut inflammation; Prevention; PEP; STI

Outcome Measures

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.

  Baseline and 12 weeks after the start of doxycycline administration

Secondary Outcomes (2)

• 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

Study Arms (2)

Doxycycline 200mg

EXPERIMENTAL

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.

Drug: Doxycycline monohydrate 200 mg

Observation with biological sampling

ACTIVE COMPARATOR

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.

Other: Observation

Interventions

Doxycycline monohydrate 200 mg DRUG

Doxycycline 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.

Also known as: Doxycycline

Doxycycline 200mg

Observation OTHER

Standard of care. Blood and rectal mucosal samples.

Also known as: Standard of Care

Observation with biological sampling

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Aspirin
• 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
• Use of experimental medications, vaccines, or biologicals in the 12 months before enrollment

Sponsors & Collaborators

• Emory University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Grady Health System (non-CRN)

Atlanta, Georgia, 30322, United States

RECRUITING

Hope Clinic

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Sexually Transmitted Diseases

Interventions

Doxycycline; Observation; Standard of Care

Condition Hierarchy (Ancestors)

Communicable Diseases; Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Methods; Investigative Techniques; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Colleen Kelley, MD, MPH

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Kelley, MD, MPH

CONTACT

404-712-1823; kelley@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 3, 2025
• First Posted: October 10, 2025
• Study Start: October 13, 2025
• Primary Completion (Estimated): April 13, 2029
• Study Completion (Estimated): April 13, 2029
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The research team will share de-identified participant data after publication of the primary results manuscript, anticipated on September 15, 2030. Data will be available indefinitely.
• Access Criteria: Interested investigators may request de-identified data for secondary analyses and/or meta-analyses by contacting Dr. Kelley via email and completing a data use agreement (DUA) with Emory University.

Locations

US (2)