Daily Doxycycline for Early Syphillis

The goal of this clinical trial is to learn if doxycycline taken as 200mg daily for 14 days is effective to treat early stage syphilis. This is different from how doxycycline is typically used for syphilis because the full doxycycline dose will be taken at the same time of day, rather than split up into a twice daily regimen. Lab data support that taking the medication as a single daily dose should be effective as treatment, but it has not been studied clinically. The main question this study aims to answer is:

Is doxycycline taken as a single daily dose of 200mg for 14 days an effective treatment for early syphilis based on a combined outcome of clinical improvement and blood test improvement?

Participants will:

1. Take doxycycline 200mg daily for 14 days
2. Submit oral and rectal swabs that test for syphilis bacteria every other day for 2 weeks, returned by mail
3. Complete 2 brief online surveys over the first 2 weeks
4. Return to the clinic for an interview and blood draw every 3 months for a maximum of 3 study visits, including the first visit

The investigators will compare the percentage of participants in the study who have response to treatment by 6 months to that of persons who have received standard (CDC-recommended) regimens. To do this, the investigators will calculate response percentage estimates following a shot of long-acting penicillin or 14 days of doxycycline 100mg twice daily from 60-person samples from the sexual health program's records.

Study Overview

• Status: Recruiting
• Conditions: Syphilis
• Intervention / Treatment: Drug: Doxycycline 200mg daily for 14 days

Detailed Description

This is an open-label prospective cohort of 15 participants diagnosed with early syphilis treated with doxycycline 200mg daily for 14 days. The outcome of interest is clinical improvement and fourfold decline in RPR by 6 months. This study will include rectal and oropharyngeal sampling with syphilis transcription-mediated amplification (TMA), every other day for the 14-day course, returned by mail. The investigators will obtain 6-month point estimates for cure following single-dose intramuscular benzathine penicillin G or 14 days of doxycycline 100mg twice daily in retrospective cohorts of 60 persons. The investigators will use binomial exact calculation with an alpha of 0.05, two-tailed, to create a point estimates of percent cure. The investigators will report TMA positivity descriptively.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Matthew Golden, MD, MPH; Phone Number: 206-744-6829; Email: golden@uw.edu
• Study Contact Backup: Name: Travis Hunt, MD; Phone Number: 206-685-4456; Email: thunt91@uw.edu

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Public Health Sexual Health Clinic
      • Contact: Jakar Delacruz; Phone Number: 206-744-3590; Email: fkajonny@uw.edu
      • Contact: Travis Hunt, MD; Phone Number: 206.685.4456; Email: thunt91@uw.edu
      • Principal Investigator: Travis J Hunt, MD
      • Principal Investigator: Matthew R Golden, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Clinical diagnosis of syphilis (primary or secondary) or laboratory-confirmed early latent syphilis. Specifically: This will include persons meeting any one of the following criteria:

1. Clinical diagnosis of primary syphilis (based on the presence of a chancre) and either a positive qualitative RPR in the absence of a prior positive RPR on their most recent serological test for syphilis or a positive darkfield microscope exam of material taken from a chancre, OR
2. Clinical diagnosis of secondary syphilis with a positive qualitative RPR in the absence of a prior positive RPR on their most recent serological test for syphilis, OR
3. A laboratory-confirmed diagnosis of early latent syphilis within one month (i.e. <31 days prior).

Exclusion Criteria:

1. age under 18
2. persons with evidence of neurosyphilis (including ocular and otic syphilis) or tertiary syphilis
3. persons who are unable to give informed consent
4. persons deemed by the study investigators to be unable to complete study follow-up visits
5. persons with an allergy to doxycycline
6. pregnant persons
7. persons with HIV who report that they are off antiretroviral medication or that they are not virologically suppressed
8. persons with other known forms of immunosuppression (e.g., persons taking systemic immunosuppressant drugs, persons with primary immunodeficiencies)
9. persons taking medications that would interact with doxycycline
10. persons whose initial RPR is lower than 1:4
11. persons currently prescribed doxy PEP
12. breastfeeding persons

Persons whose initial laboratory serological tests do not confirm the diagnosis of syphilis with an RPR of 1:4 or higher will be informed that they do not meet study criteria and advised to discontinue doxycycline 200mg once daily. Their subsequent treatment will be based on the judgement of non-research, clinical staff in the clinic and reflect shared decision making between clinical providers and their patient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Doxycycline 200mg daily for 14 days; Participants diagnosed with early syphilis (primary, secondary, or early latent) with an RPR of 1:4 or greater will receive doxycycline 200mg daily to treat syphilis. Exclusions include pregnant persons, persons under 18 years of age, and persons on doxy PEP. During the two weeks of treatment, participants will perform oral and rectal swabs for syphilis, returned at the end of the 2 weeks by mail. Participants will submit brief online surveys twice over the two weeks of treatment. Repeat blood tests for syphilis, reactive plasma reagin (RPR), will be done at follow-up visits at 3 and 6 months to monitor serological response. Participants with response at the 3-month visit will not need to come to a 6-month visit.

Drug: Doxycycline 200mg daily for 14 days; Doxycycline will be taken as a single dose of 200mg daily, rather than the current CDC-recommended 100mg twice daily regimen for early syphilis. The duration will still be 14 days of therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite clinical and serological response	Clinical response and serological response will be aggregated to arrive at one reported value, a binary outcome of "yes" (1) or "no" (0). Clinical response equates to resolution of clinical symptoms of syphilis the participants presented with, such as rash or chancre, without the development of new symptoms of syphilis. Resolution will be marked as "yes" or "no". Serological response equates to a fourfold decrease in RPR compared to the presenting RPR titer by 6 months. Resolution will be marked as "yes" or "no". Thus, to generate the composite response outcome, participants with outcomes of "yes" for both clinical response and serological response will qualify as a binary outcome of "yes" (1) . Participants who do not have outcomes of "yes" for both clinical response and serological response will qualify as a binary outcome of "no" (0).	6 months

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: Travis Hunt, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2025
• Primary Completion (Estimated): June 26, 2026
• Study Completion (Estimated): June 26, 2026

Study Registration Dates

• First Submitted: November 8, 2024
• First Submitted That Met QC Criteria: November 8, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: syphilis; doxycycline
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Sexually Transmitted Diseases, Bacterial; Treponemal Infections; Syphilis; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Doxycycline
• Other Study ID Numbers: STUDY00021340

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No