Boric Acid + Fluconazole for Vaginal Yeast Infections

(THRIVE-yeast Trial)

Overseen By Vanessa HSC Women's Health Research Program, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Manitoba

Disqualifiers: Pregnancy, Hysterectomy, BV infection, 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: 4 weeks

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore why some women experience recurrent vaginal yeast infections, while others have yeast present without symptoms. Researchers seek to understand how the yeast and bacteria in the body change after treatment with either fluconazole (an antifungal medication) or boric acid (used in vaginal suppositories). The study seeks women who have either had frequent yeast infections or have yeast without symptoms to better understand how these treatments affect the vaginal environment. Eligible participants include women who have dealt with repeated yeast infections or have never had symptoms but still have yeast present.

As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a chance to contribute to groundbreaking insights.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

A previous study found that using boric acid as a vaginal suppository safely treats recurring yeast infections. Most people tolerate it well, though some might experience mild skin irritation. Research has shown it to be an effective and affordable option for those with ongoing symptoms.

Fluconazole, another treatment for vaginal yeast infections, is also considered safe. Studies indicate it usually has few side effects. It is a well-known treatment and works well for many with yeast infections. Both treatments have good safety records, but discussing any concerns with a healthcare provider is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining boric acid with fluconazole for treating vaginal yeast infections because it offers a potentially powerful dual-action approach. While fluconazole works by inhibiting fungal cell membrane formation, boric acid acts as an antifungal by altering the pH of the vagina, creating an environment that is hostile to yeast growth. This combination could enhance efficacy, especially in cases of recurrent infections where standard treatments may not be sufficient. This innovative approach could provide quicker relief and reduce the likelihood of recurrence, which is a significant advantage over traditional treatments like fluconazole alone.

What evidence suggests that this trial's treatments could be effective for yeast infections?

This trial will evaluate the effectiveness of Boric Acid and Fluconazole for treating vaginal yeast infections. Research has shown that boric acid can be quite effective, with studies reporting cure rates ranging from 40% to 100%, and an average of 76%. This treatment also provides significant symptom relief and works well over the long term, with many patients expressing satisfaction.

Fluconazole is another treatment option in this trial. It often proves effective, with a single 150 mg dose frequently outperforming other treatments for simple infections. However, for recurrent infections, long-term use of fluconazole can help reduce their frequency, though it might not always completely cure them. Overall, both boric acid and fluconazole have demonstrated effectiveness in treating yeast infections, though their success can vary depending on the individual's condition. ^{4 6 7 8 9}

Who Is on the Research Team?

Aleeza Gerstein, PhD

Principal Investigator

University of Manitoba

Are You a Good Fit for This Trial?

This trial is for Canadian females aged 18-50 who have a yeast infection, also known as vulvovaginal candidiasis. It's not open to those who are pregnant, trying to conceive, or have had a hysterectomy.

Inclusion Criteria

I am a woman aged between 18 and 50.

Exclusion Criteria

I have had my uterus removed.

Currently pregnant

Trying to get pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with either fluconazole or boric acid to track yeast diversity and microbial community differences

4 weeks

Follow-up

Participants are monitored for changes in fungal and bacterial diversity, and host functional changes post-treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Boric Acid Supp,Vag
• Fluconazole 150 mg

Trial Overview The study compares the effectiveness of boric acid suppositories and fluconazole (a common antifungal medication) in treating yeast infections and preventing recurrence by examining changes in vaginal microbial communities.

How Is the Trial Designed?

Group I: Recurrent Infection Cohort - symptomatic Active Control 2 Interventions

Participants with a history of recurrent vulvovaginal candidiasis infections who have an active symptomatic infection when they come to clinic

Group II: Asymptomatic Cohort Active Control 1 Intervention

Participants with no history of vulvovaginal candidiasis

Group III: Recurrent Infection Cohort - asymptomatic Active Control 1 Intervention

Participants with a history of recurrent vulvovaginal candidiasis infections who do not have an active symptomatic infection when they come to clinic

Fluconazole 150 mg is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Diflucan for:

• Vulvovaginal candidiasis
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Cryptococcal meningitis
• Candidemia

Approved in United States as Diflucan for:

• Vulvovaginal candidiasis
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Cryptococcal meningitis
• Candidemia

Approved in Canada as Diflucan for:

• Vulvovaginal candidiasis
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Cryptococcal meningitis
• Candidemia

Approved in Japan as Diflucan for:

• Vulvovaginal candidiasis
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Cryptococcal meningitis
• Candidemia

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Research Manitoba

Collaborator

Trials

13

Recruited

17,500+

Manitoba Medical Service Foundation

Collaborator

Trials

19

Recruited

1,100+

Published Research Related to This Trial

A single 150 mg dose of fluconazole effectively treated vaginal candidiasis in 180 patients, with 97% showing improvement within 5 to 16 days and 88% remaining cured at long-term follow-up (27 to 62 days).

The treatment was well tolerated, with low side effects primarily limited to mild gastrointestinal issues, and only minor abnormal lab results observed in 15 patients, indicating fluconazole's safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of vaginal candidiasis with a single oral dose of fluconazole. Multicentre Study Group. [2019]

Candida species, particularly Candida albicans, are commonly found in the vagina of women, with prevalence increasing during late pregnancy and in immunosuppressed individuals, highlighting the importance of understanding host factors that influence the risk of vulvovaginal candidosis.

Treatment with antifungal agents is generally effective in over 80% of cases, but specific strains like Candida glabrata may require higher doses or alternative treatments, and self-treatment is discouraged due to the high rate of misdiagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guideline: vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis). Mendling, W., Brasch, J., Cornely, OA., et al.[2015]

Topical boric acid treatment (600 mg daily for 2 to 3 weeks) was effective in achieving clinical success in 64% of women in Detroit and 71% in Beer Sheba with Candida glabrata vaginitis, indicating its efficacy as a treatment option.

Topical flucytosine cream showed a high success rate of 90% in women whose vaginitis did not respond to previous treatments, suggesting it is a valuable alternative for azole-refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of vaginitis caused by Candida glabrata: use of topical boric acid and flucytosine. Sobel, JD., Chaim, W., Nagappan, V., et al.[2019]

In a phase 3 study involving 157 Japanese subjects, a single oral dose of 150 mg fluconazole showed a therapeutic efficacy rate of 74.7% for treating vulvovaginal candidiasis by Day 28, indicating it is an effective treatment option.

Fluconazole was well tolerated, with only mild treatment-related side effects like diarrhea and nausea reported in 1.9% of participants, and no significant safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan. Mikamo, H., Matsumizu, M., Nakazuru, Y., et al.[2022]

In a study of 40 diabetic women with vulvovaginal candidiasis (VVC), both boric acid and fluconazole showed similar long-term mycological cure rates at 3 months, with 71.4% and 63.1% remaining cured, respectively.

Despite a higher initial cure rate with boric acid (74% at 15 days), only about 46.6% of women remained cured at 3 months, indicating a need for further research into more effective long-term treatments for VVC in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged (3-month) mycological cure rate after boric acid suppositories in diabetic women with vulvovaginal candidiasis. Ray, D., Goswami, R., Dadhwal, V., et al.[2013]

In a study of 22 women with recurrent vulvovaginal candidiasis, both boric acid and itraconazole treatments showed similar effectiveness in curing the infection during the treatment period, with no significant differences in culture results or symptoms.

However, after stopping treatment, both groups experienced high relapse rates (54.5%), indicating that while boric acid is a promising option for treatment, its benefits do not persist after therapy ends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of maintenance therapy with topical boric acid in comparison with oral itraconazole in the treatment of recurrent vulvovaginal candidiasis. Guaschino, S., De Seta, F., Sartore, A., et al.[2013]

In a study of 112 diabetic patients with vulvovaginal candidiasis (VVC), those treated with boric acid vaginal suppositories showed a significantly higher mycological cure rate for C. glabrata infections compared to those treated with a single dose of oral fluconazole (63.6% vs. 28.6%).

The results suggest that boric acid is a more effective treatment option for diabetic women with C. glabrata VVC, highlighting the need for alternative therapies when azole drugs are less effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis. Ray, D., Goswami, R., Banerjee, U., et al.[2013]

A large prescription-event monitoring study involving 15,015 questionnaires confirmed that fluconazole is a safe and effective treatment for vaginal candidiasis, with no serious adverse effects reported.

Fluconazole was found to be well tolerated, even in women who took it before or during pregnancy, showing no harmful effects on pregnancy outcomes despite being contraindicated for use in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of fluconazole in the treatment of vaginal candidiasis. A prescription-event monitoring study, with special reference to the outcome of pregnancy. Inman, W., Pearce, G., Wilton, L.[2019]

In a study involving 428 patients with vaginal candidiasis, fluconazole was found to be effective in relieving symptoms, with 72% of physicians and 69% of patients reporting positive outcomes.

The majority of patients (83.5%) preferred fluconazole over other treatments they had previously received, and there were no recurrences of the infection noted at the 6-week follow-up, indicating its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose systemic oral fluconazole for the treatment of vaginal candidiasis. Kaplan, B., Rabinerson, D., Gibor, Y.[2019]

In a study of 970 patients with vaginal C. albicans infections, 7.3% were found to have clinically defined fluconazole-resistant infections, highlighting the prevalence of resistance in this population.

Treatment with vaginal boric acid was effective, achieving a mycological cure rate of 85.7% and a clinical cure rate of 73.7%, but there was a 14.3% recurrence rate within 3 months after treatment, indicating the need for ongoing management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluconazole-Resistant Candida albicans Vaginal Infections at a Referral Center and Treated With Boric Acid. File, B., Sobel, R., Becker, M., et al.[2023]

Boric acid capsules showed a high cure rate of 92% for vulvovaginal candidiasis at 7 to 10 days, significantly outperforming nystatin, which had a cure rate of 64% in the same timeframe.

Both treatments had similar speeds in alleviating symptoms, but boric acid was better accepted by patients and was more cost-effective, costing only 31 cents for fourteen capsules compared to more expensive medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of vulvovaginal candidiasis with boric acid powder. Van Slyke, KK., Michel, VP., Rein, MF.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21774671/

Boric acid for recurrent vulvovaginal candidiasis The mycologic cure rates varied from 40% to 100% in patients treated with boric acid; 4 of the 9 included case series reported statistically significant ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6878170/

Clinicians' use of Intravaginal Boric Acid Maintenance ... Average length of use was 13 months with high patient satisfaction and few adverse events.

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1155/2024/2807070

Boric Acid for the Treatment of Vaginitis: New Possibilities ... An average cure rate of 76% was found for vulvovaginal candidiasis BA treatment. Recurrent bacterial vaginosis was controlled with BA and 5- ...

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.950215/full

Effects of Boric Acid Gel on Vaginal Candida albicans ... The boric acid significantly reduced the symptoms associated with CA vaginal infection. It inhibited the CA growth, prevented vaginal lesions, promoted the ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0002937816325819

Treatment of vulvovaginal candidiasis with boric acid powder Cure rates for boric acid were 92% at 7 to 10 days after treatment and 72% at 30 days, whereas the nystatin cure rates were 64% at 7 to 10 days and 50% at 30 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10100571/

Data on safety of intravaginal boric acid use in pregnant ... BA vaginal suppositories 600mg daily for 14 days are a “safe and effective alternative (Grade 1B).” If mucosal irritation occurs dose can be ...

7. drugs.com drugs.com/mtm/boric-acid-vaginal.html

Boric acid vaginal Uses, Side Effects & Warnings The usual dosage of vaginal boric acid for a chronic vaginal yeast infection is 1 suppository inserted into the vagina once per day, for 6 days in a row. Wash ...

8. healthy.kaiserpermanente.org healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.boric-acid-for-vaginal-yeast-infection.tn9595

Boric Acid for Vaginal Yeast Infection How safe is it? When used in capsules as a vaginal suppository, boric acid is only known to sometimes cause skin irritation. But when used by mouth (internally) ...

9. my.clevelandclinic.org my.clevelandclinic.org/health/drugs/19641-boric-acid-vaginal-suppository

Boric Acid Suppositories: Uses & Side Effects Boric acid suppositories help promote a balance of acid in your vagina. They can also treat vaginal yeast infections by relieving symptoms.