Doxycycline for Sexually Transmitted Infections

Recruiting at 5 trial locations

Overseen By Ramin Azmin

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Jonathan Troy Grennan

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

Disqualifiers: Allergy to doxycycline, Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

560 Participants Needed

Trial Summary

What is the purpose of this trial?

There is a growing epidemic of the bacterial sexually transmitted infections (STIs) syphilis, chlamydia and gonorrhea worldwide; similarly concerning trends have been noted in Canada, where increases of over 160% have been seen in bacterial STIs over the last decade. In Canada, gay, bisexual, and other men who have sex with men (gbMSM) - including those living with HIV - are disproportionately impacted by bacterial STIs5,6These dramatic increases in bacterial STIs, the potential development of serious complications including AMR, and waning effectiveness of the promotion of conventional STI prevention tools (e.g. condoms), signals the need for novel STI prevention strategies and tools to mitigate STI-related complications. A rigorous randomized controlled trial will be conducted to compare STI PrEP vs. STI PEP and definitively assess the efficacy, safety, antimicrobial resistance profiles and costs associated with doxycycline-based STI prevention.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications that could lower doxycycline levels, such as barbiturates, phenytoin, and carbamazepine. If you are using isotretinoin, you will also need to stop taking it to participate.

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

Research shows that doxycycline is effective in treating infections like Chlamydia trachomatis, with a high cure rate of 100% in one study. It is also considered a good option for managing various bacterial sexually transmitted infections due to its efficacy and ease of use. ^{1 2 3 4 5}

Is doxycycline generally safe for humans?

Doxycycline is generally considered safe for humans, but it can have side effects like gastrointestinal issues, tooth development concerns in children, and photosensitivity (increased sensitivity to sunlight). Rarely, it can cause more serious effects like acute pancreatitis (inflammation of the pancreas). ^{2 6 7 8 9}

How is the drug Doxycycline Hyclate unique for treating sexually transmitted infections?

Doxycycline Hyclate is unique because it is a broad-spectrum antibiotic that can be taken orally once or twice a day, making it convenient for patients. It is effective against a wide range of bacteria, including those causing sexually transmitted infections, and has been shown to be safe with minimal side effects. Additionally, it is being explored for use as a preventive measure against STIs, although there are concerns about potential antimicrobial resistance. ^{1 2 5 9 10}

Research Team

Troy Grennan, MD

Principal Investigator

University of British Columbia

Eligibility Criteria

The DISCO trial is for gay, bisexual, and other men who have sex with men (gbMSM) over 18 years old. Participants must have had multiple male partners and at least one bacterial STI in the past year. They should not be on certain drugs that affect doxycycline levels, allergic to tetracyclines, using doxycycline regularly or taking isotretinoin.

Inclusion Criteria

I plan to be sexually active with multiple male partners this year.

I had syphilis, gonorrhea, or chlamydia treated in the last year.

I have had sexual activity with more than one male partner in the last year.

Exclusion Criteria

You are allergic to doxycycline or tetracyclines.

I am capable of becoming pregnant.

I am currently taking isotretinoin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxycycline-based STI PrEP or PEP for the prevention of bacterial STIs

12 months

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety, effectiveness, and antimicrobial resistance after treatment

60 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Doxycycline Hyclate

Trial Overview This study tests whether Doxycycline Hyclate can prevent bacterial STIs like syphilis, chlamydia, and gonorrhea in gbMSM. It's a randomized controlled trial comparing two prevention strategies: pre-exposure prophylaxis (PrEP) versus post-exposure prophylaxis (PEP).

Participant Groups

Group I: STI PrEP arm Experimental Treatment 1 Intervention

doxycycline capsules 100mg orally daily for 12 months. Though the usual treatment dose of doxycycline is 100mg twice daily

Group II: STI PEP arm Experimental Treatment 1 Intervention

doxycycline 200mg orally once within 24-72 hours following each sexual encounter deemed at risk (i.e. condomless anal or oral sex), to a maximum of six pills (i.e. 600 mg total) per week

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

Approved in United States as Doxycycline Hyclate for:

• Acne
• Malaria
• Skin infections
• Sexually transmitted infections
• Lyme disease

Approved in European Union as Doxycycline Hyclate for:

• Acne
• Malaria
• Skin infections
• Sexually transmitted infections
• Lyme disease

Approved in Canada as Doxycycline Hyclate for:

• Acne
• Malaria
• Skin infections
• Sexually transmitted infections
• Lyme disease

Who Is Running the Clinical Trial?

Jonathan Troy Grennan

Lead Sponsor

Trials

1

Recruited

560+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

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 (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]

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]

Doxycycline (Dox) demonstrated significant antiviral activity against vesicular stomatitis virus (VSV) in cultured H1299 cells, inhibiting viral replication in a dose-dependent manner at concentrations of 1.0-2.0 μg/ml.

The antiviral effect of Dox occurs during the early to mid-stages of VSV infection, indicating that it does not affect the virus's ability to enter cells, suggesting potential for Dox in treating viral infections beyond its known antibacterial properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiviral activity of doxycycline against vesicular stomatitis virus in vitro. Wu, ZC., Wang, X., Wei, JC., et al.[2015]

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, a commonly used antibiotic, was linked to a case of acute pancreatitis in a female patient who had been taking it for acne treatment, highlighting a rare but serious side effect.

The adverse reaction was confirmed as 'definite' using the WHO causality assessment and the Naranjo scale, emphasizing the importance of monitoring for potential side effects even with generally safe medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxycycline-Induced Acute Pancreatitis: A Rare Adverse Event. Rawla, P., Raj, JP.[2020]

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 (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]

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. Japan pubmed.ncbi.nlm.nih.gov

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

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

Antibiotic after sex could help curb infections. [2022]

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

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

5. England pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Antiviral activity of doxycycline against vesicular stomatitis virus in vitro. [2015]

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

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

8. Canada pubmed.ncbi.nlm.nih.gov

Doxycycline-Induced Acute Pancreatitis: A Rare Adverse Event. [2020]

9. Germany pubmed.ncbi.nlm.nih.gov

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

10. 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]