Validation of a Novel Diagnostic, Prognostic Assay for Bacterial Vaginosis

NCT02185456 | Unknown Early Phase 1 DMC

• 1 other identifier: R21AI111103-01
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Bacterial vaginosis (BV) is the commonest form of vaginitis worldwide, affecting millions of women. Unfortunately, recurrence rates of symptomatic BV remain extremely high, 30% at three months and 70-80% within a year. Given the paucity of information and data regarding pathogenesis of BV, the etiopathogenesis of recurrent bacterial vaginosis remains unknown. Accordingly, reliable, proven treatment regimens for Recurrent Bacterial Vaginosis (RBV) are not available. In 2013, the investigators published two manuscripts documenting a new qPCR based approach to BV diagnosis and potentially prognosis. The method (LbRC) measures the content of lactobacilli in vaginal samples, relative to total bacterial load. The first goal of this study are to validate that this metric is a reliable diagnostic of BV, by determining sensitivities and specificities relative to Nugent scores and Amsel criteria of healthy women and BV patients. A high LbRC score (3-4) corresponds to a healthy state. The second goal is to determine whether empirically determined "low" LbRC scores (1-2) in BV patients after treatment are indicators of recurrence, and whether preemptive action, based on this score, with more intensive treatment, delays or eliminates recurrence in these patients.

Conditions

Bacterial Vaginosis

Outcome Measures

Primary Outcomes (1)

• Diagnosis of bacterial vaginosis

  Patients and control women will be assessed monthly for bacterial vaginosis by Nugent and Amsel criteria

  Monthly for up to nine months

Secondary Outcomes (1)

• Relative quantity of Lactobacillus among total vaginal bacteria

  Monthly clinical visits and daily swabs for up to nine months

Study Arms (5)

Healthy

NO INTERVENTION

Patients with no history of bacterial vaginosis. These women will be monitored monthly and with daily self swabs.

G1 BV in clinical & molecular remission

ACTIVE COMPARATOR

Patients will receive standard of care intervention, oral metronidazole 500 mg twice a day for 7 days. They will then be monitored to confirm that initial BV treatment was effective by Nugent and Amsel, and by the qPCR test (LbRC). These will be monitored with monthly visits and daily self swabs. Those who recur with symptomatic BV may enroll in the B2 arm for more aggressive treatment.

Drug: Standard of care

G2. Molecular conversion subarm

EXPERIMENTAL

Half of G1 patients who convert to poor qPCR test results while remaining asymptomatic will be randomized into this G2 arm and receive intervention: 750 mg metronidazole/ 200 mg miconazole vaginal suppository daily for 7 days, with continued monthly visits and daily swabs.

Drug: 750 mg metronidazole/ 200 mg miconazole vaginal suppository; Drug: Standard of care

B1 Initially poor qPCR responders

ACTIVE COMPARATOR

The B1 arm are patients who enter remission after standard of care treatment, oral metronidazole 500 mg twice a day for 7 days, but who have poor initial qPCR scores. Half of such patients will be randomized into B1, half into B2. B1 patients will be monitored with monthly visits and via daily swabs, but will receive no further treatment while BV negative. Patients who recur with BV may enroll as B2 patients for more aggressive treatment.

Drug: Standard of care

B2 BV Remission to conversion

EXPERIMENTAL

A subgroup of B1 patients who convert to consistently poor qPCR scores during the study (conversion) will be randomized into Arm B2 and receive intervention: 750 mg metronidazole/ 200 mg miconazole vaginal suppository daily for 7 days. These patients will continue monthly visits and daily self swabs. B2 patients who recur with symptomatic BV will be dropped from the study and given other options for therapy.

Drug: 750 mg metronidazole/ 200 mg miconazole vaginal suppository; Drug: Standard of care

Interventions

750 mg metronidazole/ 200 mg miconazole vaginal suppository DRUG

The higher dose 750 mg metronidazole/ 200 mg miconazole vaginal suppository will be given to patients who were refractory to the standard of care therapy, oral metronidazole 500 mg twice a day for 7 days, and to asymptomatic patients in a randomized arm, who show poor responses based on the qPCR test result.

B2 BV Remission to conversion; G2. Molecular conversion subarm

Standard of care DRUG

oral metronidazole 500 mg twice a day for 7 days

Also known as: Flagyl

B1 Initially poor qPCR responders; B2 BV Remission to conversion; G1 BV in clinical & molecular remission; G2. Molecular conversion subarm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal women over the age of 18 who have BV who are willing to sign informed consent.
• Positive for all Amsel criteria:
• Vaginal pH \> 4.5
• Positive amine test
• \> 20% clue cells on wet mount
• Grayish-white adherent discharge
• Subject is willing to refrain from using any vaginal medications, douches or spermicides except for the metronidazole suppositories that are given to her for the duration of the study.
• Subject is willing to use supplied non-lubricated condoms when sexually active. But not to have sexual intercourse within 48 hours of any Study Visit.
• Subject to refrain from alcohol for 24 hours prior to the first 7 days of the metronidazole treatment and for 48 hours after completion of this treatment.
• Enrollees for the healthy Group H in the study must be premenopausal and have not experienced any vaginitis in the past year.
• Subject will be encouraged to have a full clinical examination, but if she declines, she must have a self-swab evaluation that is normal (no yeast, no clue cells, normal flora, no parabasal cells and no trichomonads) and will be retained in Group H if her Nugent score is 3 or less.
• Subject must be willing to obtain daily samples and return monthly with the samples for a self-swab evaluation and a replenishment of the daily swab supplies. Healthy women will continue for as long as they are willing up to 9 months.
• Healthy women will be asked to use the supplied non-lubricated condoms, but will not be dropped from the study if they do not.
• Must be using some form of contraception if sexually active.

You may not qualify if:

• Mixed vaginal infection at time of enrollment.
• Pregnancy, nursing or planning on getting pregnant.
• Subject on anticoagulation therapy, lithium therapy or Antabuse therapy.
• Vaginal bleeding at time of enrollment
• Allergy to metronidazole
• Use of any vaginal antibiotics or antifungals in the previous 10 days, from enrollment.
• Must not require treatment for an abnormal Pap smear or genital cancer.
• Must abstain from vaginal douching during enrolled period.
• Has a vaginal infection at enrollment
• Pregnant, nursing or planning on becoming pregnant in the next year.
• Vaginal bleeding at enrollment
• Must not require treatment of any genital cancer or abnormal pap smear
• Should abstain from douching throughout the length of the study.

Sponsors & Collaborators

• Wayne State University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

WSU Tolan Park Medical Building 3901 Chrysler Service Drive, Suite 4A

Detroit, Michigan, 48201, United States

RECRUITING

Related Publications (4)

• Aguin T, Akins RA, Sobel JD. High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study. Sex Transm Dis. 2014 May;41(5):290-1. doi: 10.1097/OLQ.0000000000000123.

  PMID: 24722380 BACKGROUND

• Aguin TJ, Akins RA, Sobel JD. High-dose vaginal metronidazole for recurrent bacterial vaginosis--a pilot study. J Low Genit Tract Dis. 2014 Apr;18(2):156-61. doi: 10.1097/LGT.0b013e31829a5558.

  PMID: 23994951 BACKGROUND

• Lambert JA, John S, Sobel JD, Akins RA. Longitudinal analysis of vaginal microbiome dynamics in women with recurrent bacterial vaginosis: recognition of the conversion process. PLoS One. 2013 Dec 20;8(12):e82599. doi: 10.1371/journal.pone.0082599. eCollection 2013.

  PMID: 24376552 BACKGROUND

• Lambert JA, Kalra A, Dodge CT, John S, Sobel JD, Akins RA. Novel PCR-based methods enhance characterization of vaginal microbiota in a bacterial vaginosis patient before and after treatment. Appl Environ Microbiol. 2013 Jul;79(13):4181-5. doi: 10.1128/AEM.01160-13. Epub 2013 Apr 26.

  PMID: 23624483 BACKGROUND

MeSH Terms

Conditions

Vaginosis, Bacterial

Interventions

Metronidazole; Standard of Care

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Robert A Akins, PhD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• Jack D Sobel, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert A Akins, PhD

CONTACT

313-577-0419; rakins@med.wayne.edu

Jack D Sobel, MD

CONTACT

313-745-7105; jsobel@med.wayne.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator-coinvestigator

Study Record Dates

• First Submitted: July 2, 2014
• First Posted: July 9, 2014
• Study Start: September 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: March 1, 2016
• Last Updated: November 7, 2014

Record last verified: 2014-11

Locations

US (1)