Randomized Controlled Trial of Treatment of Male Partners of Women With BV

This study will be performed as a phase III randomized, double-blinded trial to evaluate the
efficacy of 1) metronidazole 500 mg PO BID for 7 days versus 2) placebo capsules alone for
treatment of the male sexual partner of women with recurrent BV. The primary outcome is the
rates of recurrent BV between these two groups. Although this is a phase III study we will
carefully monitor potential toxicity in the males since it is currently not standard of care
to treat males for this indication.

Women with symptomatic BV defined by Amsel criteria 1 and no evidence of STD will be invited
to participate. Inclusion criteria are that the woman be at least 18 years of age,
heterosexual, have symptoms of vaginal odor and/or discharge, meet the modified clinical
(Amsel) criteria for BV (all must have a vaginal pH of >4.5, a positive whiff test, and clue
cells to be eligible), have an enrollment Nugent score of 7 or greater, and a history of 2 or
more episodes of BV in the previous year. She must have a regular current sex partner who
would be willing to participate. We will exclude women who have had recurrent BV for greater
than 3 years as well as women who have failed previous treatment studies since it is likely
that these women are having recurrent BV as a result of relapse of the BV biofilm as opposed
to reinfection.

Follow-up visits will be conducted at day 21, 8 and 16 weeks. At each follow-up visit, a
questionnaire will be administered, diary reviewed, pelvic examination conducted and
specimens (Gram stain, Amsel criteria, G vaginalis culture and detection of novel organisms)
obtained as done at the enrollment visit. Participants will be asked to return the medication
packages, a standard way of assessing adherence to the regimen. Cure will be ascertained
using the clinical criteria for BV of Amsel 1 as well as the Nugent scoring system 16. The
persistence or disappearance of specific organisms will be analyzed in relationship to these
standard definitions of cure. Women who fail initial therapy or have recurrence of
symptomatic BV during the course of the study will be re-treated with 7 days of metronidazole
and dropped from the study at that time. Any woman found to have a positive screening test
for gonorrhea or chlamydia will be treated appropriately and instructed to notify her partner
of the need to be treated. Women with intercurrent vaginal yeast infections, which may occur,
will be treated with oral fluconazole and continued in the study. Women with a positive
culture for trichomonas will be dropped from the study as their male partners will require
treatment with metronidazole.

Male Study Procedures

Males referred by their female sexual partner will be seen within 48 hours of enrollment of
the female. Males will be consented and asked behavioral and historical questions using a
gender appropriate questionnaire, with special emphasis on number of current sexual partners.
A couple verification screening tool will be utilized to be certain they are current sexual
partners48. The confidentiality of their answers will be emphasized. They will be examined
and a urethral swab specimen obtained to be used for G vaginalis culture and then archived.
Following the swabs, two external swabs from the coronal sulcus and a 10 ml first void urine
specimen will be obtained. These specimens will also be used for G vaginalis culture and
archived for possible use in detection of novel organisms. The urine will also be used for
NAATS for N gonorrhoeae and C trachomatis and for the determining the presence or absence of
Gardnerella biofilm24. They will then be randomized to one of two treatment arms:

1. Metronidazole 500 mg PO twice a day for 7 days .

2. Placebo capsules PO twice a day for 7 days.

Both arms will also contain an instruction sheet on metronidazole.

Inclusion Criteria: Female

1. At least 18 years of age (19 years of age in Alabama due to State law)

2. Sexual partner to a female who meets study eligibility

3. Willingness to provide informed consent

4. Willingness to abstain from sexual intercourse or use condoms {during the study}

5. Willingness to abstain from alcohol for the first week of the study

Inclusion Criteria: Male

1. At least 18 years of age (19 years of age in Alabama due to State law)

2. Heterosexual with a regular partner

3. History of 2 or more episodes of BV in the previous 12 months

4. Symptoms of BV including vaginal discharge and/or odor

5. Positive Amsel criteria for BV including vaginal pH >4.5, positive whiff test,
presence of clue cells

6. Willingness to provide informed consent

7. Willingness to abstain from sexual intercourse or use condoms {during the study}

8. Willingness to abstain from alcohol for the first week of the study

Exclusion criteria (both genders)

1. Allergy to metronidazole

2. Failure of the male partner to keep his appointment to be seen within 48 hours

3. Pregnant or breast feeding (females)

4. HIV or other chronic disease which in the opinion of the investigator would interfere
with the ability to participate in this study

5. Subject requires concurrent lithium, coumadin, dilantin, or antabuse

6. Presence of trichomonas on wet prep of vaginal fluid (females)

7. Women with a history of recurrent BV for >3 years or women who have failed previous
treatment studies for BV