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

Trial Summary

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.

What data supports the effectiveness of the drug doxycycline for sexually transmitted infections?

Doxycycline has been shown to be effective in treating sexually transmitted infections like Chlamydia trachomatis and gonorrhea, with high cure rates reported in studies. It is well-tolerated, has good tissue penetration, and is effective against several bacterial infections, making it a strong option for managing STIs. ^{1 2 3 4 5}

Is doxycycline generally safe for humans?

Doxycycline is generally well tolerated in humans, but it can cause stomach upset, nausea, and diarrhea. New formulations have been developed to reduce these side effects. It is not recommended for children, pregnant women after the second trimester, and breastfeeding mothers due to potential risks. ^{6 7 8 9 10}

How does the drug doxycycline differ from other treatments for sexually transmitted infections?

Doxycycline is unique because it is a broad-spectrum antibiotic that can be taken orally once or twice daily, making it convenient for patients. Its high tissue penetration and long half-life make it effective against intracellular pathogens, and it is being considered for both treatment and prevention of sexually transmitted infections, especially in light of rising resistance to other antibiotics. ^{1 2 4 5 11}

What is the purpose of this trial?

Rates of bacterial sexually transmitted infections (STIs) are rising globally, demanding innovative interventions beyond the scope of current efforts to prevent STIs. The United States Doxycycline Post-exposure Prophylaxis (DoxyPEP) Study has demonstrated the efficacy of doxycycline post-exposure prophylaxis (PEP) among men who have sex with men and transgender women; but puzzlingly, doxycycline PEP was found ineffective in cisgender women in the Kenyan doxycycline Post-Exposure Prophylaxis (dPEP) study, with preliminary data suggesting the low medication adherence may explain the null result. By study end, the investigators will have developed adherence measurement methods for doxycycline in hair, blood, and urine, and will use these techniques to help interpret the Kenyan dPEP study, and to examine the relative performance of these methods within the United States DoxyPEP trial, establishing adherence metrics for current and future rollout studies of doxycycline post-exposure prophylaxis

Research Team

Matthew Spinelli, MD, MAS

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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.

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

I am a transgender woman consistently using estrogen hormone therapy.

Exclusion Criteria

Doxycycline is detectable in my hair.

Pregnancy or plans to become pregnant

Known hypersensitivity reaction to doxycycline

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 (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]

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 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 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 (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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A systematic review of the impacts of oral tetracycline class antibiotics on antimicrobial resistance in normal human flora. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Doxycycline in the management of sexually transmitted infections. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Comparison of spiramycin and doxycycline for treatment of Chlamydia trachomatis genital infections. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Doxycycline in the Treatment :uncomplicated Gonorrohea. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

[Clinical studies on doxycycline in the treatment of nongonococcal urethritis by Chlamydia trachomatis]. [2020]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline. [2018]

7. England pubmed.ncbi.nlm.nih.gov

The use and safety of doxycycline hyclate and other second-generation tetracyclines. [2022]

8. France pubmed.ncbi.nlm.nih.gov

[Doxycycline]. [2013]

9. Australia 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). [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Antibiotic after sex could help curb infections. [2022]