Doxycycline for Sexually Transmitted Infections

(DOT-Doxy-PEP Trial)

Overseen By Shivani Mahuvakar

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, San Francisco

Must be taking: Gender affirming hormones

Must not be taking: Doxycycline

Disqualifiers: Pregnancy, Liver disease, Hypersensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests doxycycline, a common antibiotic, to determine its effectiveness in preventing sexually transmitted infections (STIs). Researchers aim to identify the optimal dosing schedule: daily, three times a week, once a week, or every other week. The study also seeks to develop methods for measuring adherence to the medication plan using hair, blood, and urine samples. Individuals who have had an STI in the past two years or have a partner diagnosed with an STI in the past year may qualify for this trial, provided they are willing to use condoms and provide samples. As an Early Phase 1 trial, this research focuses on understanding doxycycline's effects in people, offering participants a chance to contribute to innovative STI prevention strategies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are a transgender participant, you must continue using your gender-affirming hormone therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that doxycycline is generally well-tolerated as a treatment. The Centers for Disease Control and Prevention (CDC) states that taking 200 mg of doxycycline after sex can reduce infections like syphilis and chlamydia by more than 70%. Other studies have found that using doxycycline as a preventive measure after exposure (PEP) can also lower the risk of bacterial sexually transmitted infections (STIs) in certain groups, such as men who have sex with men and transgender women.

Doxycycline is commonly used to treat various bacterial infections and is considered safe for both short and long-term use, such as in preventing malaria. Most people tolerate the drug well, but some might experience mild side effects, such as an upset stomach or increased sensitivity to sunlight. These side effects are usually manageable and temporary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about exploring doxycycline dosing regimens for sexually transmitted infections because this antibiotic offers flexible and potentially more convenient dosing options compared to traditional treatments. Unlike standard regimens that often require frequent dosing, this trial investigates varied schedules, including daily, three-times weekly, weekly, and every other week dosing. These options could potentially improve adherence and fit better into patients' lifestyles, which is crucial for effective treatment. By examining these different dosing frequencies, the study aims to identify the most efficient and patient-friendly way to use doxycycline, possibly enhancing effectiveness while minimizing side effects.

What evidence suggests that this trial's treatments could be effective for preventing STIs?

Research has shown that doxycycline can help reduce bacterial sexually transmitted infections (STIs). Studies found that taking 200 mg of doxycycline within 72 hours after sex can lower the risk of infections like syphilis and chlamydia by over 70%. This effect has been observed in men who have sex with men and transgender women. However, limited information exists on its effectiveness for cisgender women, possibly due to challenges in adhering to the medication schedule. Overall, using doxycycline after exposure has shown great potential in reducing STI rates when used correctly.

In this trial, participants will be randomized into different dosing schedules to evaluate doxycycline's effectiveness in preventing STIs. The trial will compare daily dosing, three-times weekly dosing, weekly dosing, and every other week dosing to determine the most effective regimen. ^{1 3 5 6 7}

Who Is on the Research Team?

Matthew Spinelli, MD, MAS

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for men who have sex with men and transgender women to test if taking a doxycycline pill after sexual contact can prevent bacterial STIs. Participants should be willing to provide samples for adherence measurement. The study doesn't include cisgender women due to previous findings.

Inclusion Criteria

I am a transgender man using testosterone and my levels show consistent use.

Not currently enrolled in other STI prevention studies

I haven't had an STI in the last 2 years and my partner hasn't had one in the last year.

Exclusion Criteria

Doxycycline is detectable in my hair.

Pregnancy or plans to become pregnant

Known hypersensitivity reaction to doxycycline

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to different dosing schedules of doxycycline for six weeks

6 weeks

Pharmacokinetic Washout

Doxycycline concentrations are measured in hair, urine, and plasma samples using liquid chromatography tandem mass spectrometry

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Doxycycline

Trial Overview The study tests the effectiveness of a doxycycline pill as post-exposure prophylaxis (PEP) against STIs in high-risk populations. It also aims to develop methods for measuring medication adherence using hair, blood, and urine samples.

How Is the Trial Designed?

Group I: Daily Dosing Active Control 1 Intervention

Participants will be randomized to take once daily doxycycline 200mg for six weeks.

Group II: Three-times Weekly Dosing Active Control 1 Intervention

Participants will be randomized to take one doxycycline 200mg dose three times a week (Monday, Wednesday, and Friday) for six weeks.

Group III: Weekly Dosing Active Control 1 Intervention

Participants will be randomized to take one doxycycline 200mg dose once week.

Group IV: Every Other Week Dosing Active Control 1 Intervention

Participants will be randomized to take one doxycycline 200mg dose every other week.

Doxycycline is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in European Union as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Canada as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Japan as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Doxycycline is a well-established, broad-spectrum antibiotic that is effective against various bacterial infections, including sexually transmitted infections (STIs), and is particularly beneficial due to its high tissue diffusion and long half-life, allowing for convenient oral dosing.

With the rise of antibiotic resistance in first-line STI treatments, doxycycline is being reconsidered as a safe and effective option for managing STIs, especially in populations at higher risk, such as men who have sex with men (MSM) and those living with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxycycline in the management of sexually transmitted infections. Peyriere, H., Makinson, A., Marchandin, H., et al.[2019]

In a study of 50 uncomplicated male gonorrhea cases treated with doxycycline, the treatment showed an 88% success rate, with 44 out of 50 patients responding well to the therapy.

The treatment regimen involved a total of 400 mg of doxycycline administered intravenously over three days, and side effects were minimal, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxycycline in the Treatment :uncomplicated Gonorrohea. Wadhwa, SL., Marquis, L.[2019]

Doxycycline hyclate (DH) has a favorable safety profile, especially in its delayed-release form (Doryx), compared to the standard powder form (Vibramycin), making it a safer option for treating conditions like acne and rosacea.

Despite historical safety concerns associated with tetracyclines, including gastrointestinal issues and effects on tooth development, subantimicrobial dosing of DH has shown to be effective and safe for acne treatment, supporting its continued use in dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use and safety of doxycycline hyclate and other second-generation tetracyclines. Sloan, B., Scheinfeld, N.[2022]

Doxycycline (Doxy-PEP) has been shown to effectively prevent bacterial sexually transmissible infections (STIs) like chlamydia, gonorrhoea, and syphilis in men who have sex with men with a history of multiple STIs.

Concerns remain regarding potential adverse effects of Doxy-PEP, including the risk of developing antimicrobial resistance and disrupting the microbiome, which clinicians need to discuss with patients considering this preventive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim position statement on doxycycline post-exposure prophylaxis (Doxy-PEP) for the prevention of bacterial sexually transmissible infections in Australia and Aotearoa New Zealand - the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM). Cornelisse, VJ., Ong, JJ., Ryder, N., et al.[2023]

A systematic review of 7 studies involving oral tetracycline-class antibiotics, including doxycycline, indicated that these antibiotics can increase resistance to tetracyclines in normal flora, particularly in subgingival, gastrointestinal, and upper respiratory tract bacteria.

While some studies showed a transient increase in non-tetracycline resistance, the overall impact on non-tetracycline AMR was minimal, suggesting that the use of doxycycline for STI prophylaxis may require careful monitoring of antimicrobial resistance in commensal bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the impacts of oral tetracycline class antibiotics on antimicrobial resistance in normal human flora. Truong, R., Tang, V., Grennan, T., et al.[2022]

Doxycycline is an effective antibiotic for treating various infections, particularly respiratory tract diseases like pneumonia, as demonstrated in a study involving 49 patients.

The drug shows good safety and compatibility, especially in children, and achieves effective serum levels when administered at a dose of 4 mg/kg in two injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. Weingärtner, L., Straube, D., Baum, W., et al.[2013]

In a study involving 111 healthy volunteers, enteric-coated doxycycline hyclate pellets in capsules were found to cause significantly fewer gastrointestinal adverse reactions compared to doxycycline monohydrate tablets, with only 43% of participants reporting side effects versus 66% for monohydrate.

The new formulation demonstrated improved tolerability, particularly reducing incidents of abdominal pain, nausea, and vomiting, making it a safer option for patients requiring doxycycline therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline. Järvinen, A., Nykänen, S., Paasiniemi, L., et al.[2018]

Doxycycline is effective against a wide range of bacterial infections and is particularly notable for its safety profile, as it does not require dosage adjustments in patients with renal failure.

It is well tolerated with common side effects like stomach upset and nausea, but new formulations are available to minimize these issues; however, it is contraindicated in children and pregnant or breastfeeding women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Doxycycline]. Aupee, O., Almeras, D., Le Garlantezec, P., et al.[2013]

Doxycycline (200 mg/day for 2 weeks) effectively eradicated Chlamydia trachomatis in 89% of patients by the 3rd day and maintained a 100% eradication rate by the 14th day, demonstrating its efficacy in treating nongonococcal urethritis.

The treatment was well-tolerated with no reported side effects, and a significant reduction in symptoms was observed, with 83% of patients symptom-free by the 7th day and 100% by the 14th day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical studies on doxycycline in the treatment of nongonococcal urethritis by Chlamydia trachomatis]. Ito, Y., Katoh, N., Takeda, A., et al.[2020]

Doxycycline has been shown to lower the risk of sexually transmitted diseases (STDs), making it a potentially effective preventive treatment.

Concerns exist regarding the possibility that widespread use of doxycycline could lead to increased drug resistance, which may undermine its effectiveness in treating infections in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic after sex could help curb infections. Cohen, J.[2022]

In a study of 367 patients with Chlamydia trachomatis infections, both doxycycline (100 mg) and spiramycin (1 g) were found to be highly effective, with cure rates of 100% for doxycycline and 98% for spiramycin, indicating that both treatments are viable options.

Spiramycin was associated with a higher incidence of dysethesias in female patients, although these side effects resolved after treatment, suggesting that while effective, further research is needed to explore its safety profile, especially in shorter treatment durations and during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of spiramycin and doxycycline for treatment of Chlamydia trachomatis genital infections. Dylewski, J., Clecner, B., Dubois, J., et al.[2021]

Citations

1. cdc.gov cdc.gov/mmwr/volumes/73/rr/rr7302a1.htm

CDC Clinical Guidelines on the Use of Doxycycline .. ... 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12313191/

Doxycycline post-exposure prophylaxis is effective and ... Doxycycline post-exposure prophylaxis significantly reduced bacterial STI generally, and Chlamydia trachomatis specifically, in a diverse group ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2211934

Postexposure Doxycycline to Prevent Bacterial Sexually ... A pilot study of doxy-PEP involving 30 MSM living with HIV infection showed a 73% reduction in a composite end point of bacterial STIs, ...

4. nature.com nature.com/articles/s41467-025-64261-w

Bacterial sexually transmitted infections and related ... Increases in doxycycline use exceeded anticipated reductions in STI-related prescribing of cephalosporins, macrolides, and penicillins by 16–69- ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1201971224002571

Doxycycline prophylaxis for the prevention of sexually ... 200 mg doxycycline after sex significantly reduced the risk of chlamydia and syphilis. No serious adverse events were reported with the use of doxycycline ...

6. cdc.gov cdc.gov/sti/hcp/doxy-pep/index.html

Doxy PEP for Bacterial STI Prevention Doxy PEP has proven to reduce the risk of getting some bacterial STIs for gay, bisexual, and other men who have sex with men and transgender women at increased ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7319058/

Doxycycline Prophylaxis for Bacterial Sexually Transmitted ... Doxycycline prophylaxis for syphilis and chlamydia has been effective in initial trials. Future research should focus on populations with high incidence/ ...