Summary

for males ages 18 years and up (full criteria)
healthy people welcome
at UCSF
study started
estimated completion
Anne Luetkemeyer, MD(ucsf)

Description

Summary

The purpose of this study is to understand if taking an antibiotic called doxycycline by mouth as soon as possible after sexual contact without a condom can reduce the risk of sexually transmitted infections (STIs), including gonorrhea, chlamydia and syphilis. The study will also look at the safety of doxycycline PEP and the impact that PEP may have on the bacteria that cause STIs as well as on bacteria that normally live on the body. While doxycycline is approved by the Food and Drug Administration (FDA), taking doxycycline immediately after sexual contact to prevent infection is investigational and is not approved by the FDA for this use. Participants will take part in the study for 1 year.

Details

The overarching goal is to assess the effectiveness of doxycycline PEP on incidence of STIs and tetracycline resistance among STIs and commensal bacteria to inform public health policy. Participants will be randomized 2:1, with a greater number receiving doxycycline PEP compared with the standard of care control, to maximize data on safety, tolerability, adherence coverage of sexual acts, and resistance data in participants randomized to doxycycline PEP, without negatively impacting power to measure effectiveness. Participants will be counseled about the preliminary effectiveness data from IPERGAY, and the potential for antimicrobial resistance (AMR) in STIs or other bacteria. Possibility of unreported doxycycline us in the control arm (contamination) will be monitored through retrospective batch testing of doxycycline metabolites in hair, to detect doxycycline use in the prior 3 months. 53

Eligible participants randomized 2:1 to receive PEP will receive open-label doxycycline 200 mg to be taken ideally within 24 hours but no later than 72 hours after condomless sexual contact (oral or anal). 200 mg of doxycycline will be taken at most once per 24 hour period regardless of the number of sexual acts occurring during this time period. Sexual activity will be recorded for both arms of the study (doxycycline PEP and control condition) by the participant using a smartphone application that will be adapted for study use; this will enable comparable assessment of risk in the two arms. PEP pill-taking will also be measured by the app to enable assessment of coverage of sex acts by PEP. Sexual activity and adherence will also be assessed in person at quarterly visits. STI testing will be conducted quarterly from three anatomic sites (pharyngeal, rectal and urinary) and blood for syphilis testing. Participants with a positive STI test will return for STI treatment and for swabs of the affected site for resistance testing; culture based for gonorrhea (GC) and molecular methods for CT and syphilis. Those with a serologic test that indicates a new syphilis infection will have swabs of any current active lesion as well as mucosal swabs from the oropharynx. Nares and oropharyngeal swabs will be obtained at baseline, 6 and 12 months to evaluate tetracycline resistance in S. aureus among carriers and in commensal Neisseria species.

Stool samples from 100 participants on the doxycycline PEP arm - 50 MSM living with HIV and 50 HIV uninfected MSM on pre-exposure prophylaxis (PrEP) - will be collected at baseline, 6 and 12 months to evaluate effects of intermittent doxycycline on the gut resistome, using 16s ribosomal RNA amplification to study tetracycline resistance genes. Rectal swabs will be collected and archived in all participants at baseline, 6, and 12 months for future studies of the impact of doxycycline PEP on the enteric microbiome and resistome.

Study population: This study will enroll 390 HIV-infected participants and 390 persons taking PrEP, for a total sample size of 780. An approximately equal number of participants in each of these cohorts (and in each study arm) will be enrolled in San Francisco and Seattle.

Current or planned initiation of PrEP use is an eligibility criterion for enrollment, because this population of MSM has high rates of STIs and are typically seen quarterly for PrEP visits. However, participants may opt to stop PrEP use at any time during the study without affecting their involvement in the study. Any HIV-uninfected participants who subsequently seroconvert will be managed clinically by the study site according to local practice (appropriate counseling, clinical evaluation and immediate linkage to clinical and psychosocial services). These participants will also be retained in the study unless they choose to discontinue study participation.

Keywords

Gonorrhea Chlamydia Syphilis HIV Post-Exposure Prophylaxis Men who have sex with men (MSM) Doxycycline HIV Pre-Exposure Prophylaxis Sexually transmitted infection Infection Sexually Transmitted Diseases Doxycycline Hyclate Delayed-Release 200 mg Doxy PEP

Eligibility

You can join if…

Open to males ages 18 years and up

  • Willing and able to give written informed consent
  • Age ≥ 18 years
  • Male sex at birth
  • Previously HIV-diagnosed OR HIV-seronegative at the time of last test within the past month and a current prescription for PrEP (both daily or event-driven permitted) or plan to start PrEP within 30 days after the enrollment visit
  • Condomless anal or oral sexual contact with ≥ 1 male sex-at-birth partners in the past 12 months
  • Diagnosed with GC, CT or early syphilis (primary, secondary or early latent) in the past 12 months. Note: self report of STI is acceptable if documentation not available.
  • Willing to use a smartphone app to record sexual practices (all participants) and doxycycline PEP (if assigned to PEP arm) if the participant possesses a smartphone

Note: Possession of smartphone is not required for study participation. Study personnel will assist in obtaining a smartphone through locally available resources if participant does not have a phone.

You CAN'T join if...

  • Allergy to tetracycline class
  • Current medications which may impact doxycycline metabolism or that are contraindicated with doxycycline, as per the prescribing information. These include systemic retinoids, barbiturates, carbamazepine, and phenytoin.
  • Anticipated use of doxycycline during the coming 12 months for non-STI prevention (e.g., acne treatment).

Locations

  • University of California, San Francisco / Zuckerberg San Francisco General Hospital/UCSF not yet accepting patients
    San Francisco California 94110 United States
  • San Francisco City Clinic / San Francisco Department of Public Health not yet accepting patients
    San Francisco California 94103 United States

Lead Scientist

  • Anne Luetkemeyer, MD (ucsf)
    Associate Professor, Medicine. Authored (or co-authored) 50 research publications. Research interests: Tuberculosis · HIV · Hepatitis C · Viral hepatitis · Hepatitis Elimination

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT03980223
Phase
Phase 4
Study Type
Interventional
Last Updated