Doxycycline for Syphilis Prevention

Overseen By Troy Grennan, MD

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: British Columbia Centre for Disease Control

Must be taking: Doxycycline

Must not be taking: Barbiturates, Phenytoin, Carbamazepine, Isotretinoin

Disqualifiers: Allergy to doxycycline, Myasthenia gravis, others

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether taking doxycycline daily can prevent syphilis in HIV-positive men who have sex with other men. As syphilis rates rise, researchers aim to determine if doxycycline can serve as a new preventive measure. Participants will take either a doxycycline pill or a placebo (a pill that looks the same but contains no medicine) daily. Ideal candidates for this trial are HIV-positive men who have previously had syphilis and engaged in condomless sex with other men in the past six months. As a Phase 4 trial, this research seeks to understand how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

If you are taking medications like barbiturates, phenytoin, carbamazepine, or isotretinoin, you may need to stop them because they can affect doxycycline levels. The trial does not specify about other medications, so it's best to discuss with the trial team.

What is the safety track record for doxycycline?

Research shows that doxycycline is usually easy to tolerate when used to prevent sexually transmitted infections (STIs). Studies have found that people taking doxycycline after exposure to STIs had a lower risk of infections like chlamydia, gonorrhea, and syphilis. The drug has also been used safely for other purposes, such as preventing malaria, which supports its safety.

Participants in these studies did not report major side effects, indicating that doxycycline is a safe choice for many. This is reassuring, especially for those considering it to prevent syphilis. However, as with any medication, discussing possible side effects and personal health concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for syphilis, which primarily involve antibiotics like penicillin, doxycycline offers a unique approach as a preventive measure. Researchers are excited about doxycycline because it is taken once daily, mirroring the schedule of HIV PrEP, which may improve adherence. Additionally, doxycycline's ability to work as a prophylactic treatment for other conditions like malaria suggests its potential effectiveness in preventing syphilis, making it an intriguing alternative to traditional treatment methods.

What evidence suggests that doxycycline might be an effective treatment for syphilis prevention?

Research has shown that doxycycline can help prevent sexually transmitted infections (STIs) like syphilis. Studies found that taking 200 mg of doxycycline within 72 hours after sex can reduce the risk of syphilis by over 70%. It also helps reduce other STIs, such as chlamydia and gonorrhea. In this trial, participants in the Doxycycline arm will receive 100 mg of doxycycline daily, which is generally well-tolerated and effective as a preventive measure when taken regularly. This makes it a promising option for preventing syphilis, especially for those at higher risk. Participants in the Placebo arm will receive a placebo capsule identical in appearance, taste, and size to the doxycycline capsule. ^{1 2 4 5 6}

Who Is on the Research Team?

Troy Grennan, MD

Principal Investigator

BC Centre for Disease Control

Are You a Good Fit for This Trial?

The trial is for HIV-positive gay, bisexual, and other men who have sex with men (gbMSM) over 18 years old. Participants must have had condomless anal sex in the past 6 months and a recent syphilis diagnosis. They can't join if they're allergic to doxycycline or tetracyclines, have myasthenia gravis, use isotretinoin or certain other medications.

Inclusion Criteria

Able to provide informed consent

I identify as a man who has sex with men.

I have had unprotected anal sex with a man in the past 6 months.

Exclusion Criteria

I am not taking medications like barbiturates, phenytoin, or carbamazepine.

I am capable of becoming pregnant.

I am currently taking isotretinoin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily doxycycline or placebo for syphilis prevention

48 weeks

Regular visits for monitoring adherence and drug levels

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Doxycycline
• Placebo

Trial Overview This study tests whether taking daily doxycycline can prevent syphilis in high-risk gbMSM compared to a placebo. It builds on previous research suggesting that this antibiotic could be an effective preventive measure against sexually transmitted infections.

How Is the Trial Designed?

Group I: Doxycycline arm Experimental Treatment 1 Intervention

Participants in this intervention group will receive doxycycline 100mg orally daily, which is available as a 100mg capsule. This single daily dose was chosen to maximize adherence, given the common use of once-daily Human Immunodeficiency Virus (HIV) pre-exposure prophylaxis (PrEP), as well as its efficacy as once-daily prophylaxis against malaria and its utility as dosing as infrequent as once weekly for another spirochete infection, leptospirosis.

Group II: Placebo arm Placebo Group 1 Intervention

Participants in this control group will receive a placebo capsule identical in appearance, taste, and size to the capsule provided to the intervention group.

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?

British Columbia Centre for Disease Control

Lead Sponsor

Trials

11

Recruited

2,600+

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. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK597440/

Doxycycline Post-Exposure Prophylaxis to Prevent Bacterial ... Among participants with HIV, doxy-PEP did not significantly reduce incident early syphilis or urethral or pharyngeal chlamydia or gonorrhea.

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

Bacterial sexually transmitted infections and related ... 1: Incidence of gonorrhea, chlamydia, and syphilis preventable by direct effects of doxycycline post-exposure prophylaxis (doxyPEP). figure ...

4. academic.oup.com academic.oup.com/cid/article/70/6/1247/5557867

Doxycycline Prophylaxis for Bacterial Sexually Transmitted ... Those taking Doxy PEP had lower STI incidence (hazard ratio, 0.57; P = .014). Chlamydia trachomatis and syphilis diagnoses were significantly lower in the ...

5. doh.wa.gov doh.wa.gov/you-and-your-family/illness-and-disease-z/sexually-transmitted-infections-sti/doxycycline-postexposure-prophylaxis-doxy-pep

Doxycycline Postexposure Prophylaxis (doxy PEP) Doxy PEP is reported to be tolerated and to significantly reduce the acquisition of chlamydia (CT), gonorrhea (GC), and syphilis when taken within 72 hours ...

6. ucsf.edu ucsf.edu/news/2023/07/425786/dont-take-chances-why-doxycycline-great-bet-against-stis

Don’t Take Chances: Doxycycline A Great Bet Against STIs In several studies, doxy-PEP reduced the risk of gonorrhea by about 55-60% and decreased the chances of developing chlamydia and syphilis by ...