- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04046900
Vaginal Microbiota Transplant (MOTIF)
Vaginal Microbiota Transplant to Promote Lactobacillus-dominant Cervicovaginal Communities
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The investigators propose a randomized, double-blind, placebo-controlled trial to evaluate the safety of vaginal microbiota transplant (VMT) in women with recurrent bacterial vaginosis (BV), and to assess the ability of antibiotic treatment plus vaginal microbiota transplant to establish a Lactobacillus-dominant vaginal community as compared to antibiotic treatment alone. The underlying hypothesis is that the VMT will lead to less inflammation and higher prevalence of vaginal Lactobacillus compared to antibiotics alone. The transplant material will be vaginal fluid collected from healthy donors using a disposable menstrual cup. Donors undergo extensive testing for possible infections to ensure the safety of the donated material.
Study Visits and Procedures: In addition to the pre-screening eligibility phone call and screening visit, there will be two treatment study visits and six post-VMT follow up visits at weeks 3, 5, 7, 11, 15, and 27. The baseline visit will occur within 45 days of the screening visit.
Phone Screen: A brief phone discussion to explain approach and alternatives (see details below in "Technical Methods"). A set of short screening questions will be asked to identify women with clear exclusion criteria for participation.
Visit 1, Screening Visit: At the screening visit, after written informed consent is obtained, the information from the pre-screening questionnaire will be reviewed with the subject and updated as necessary. Blood and vaginal specimens will be collected. The VMT process will be explained in detail and subjects will have the opportunity to inspect an example applicator if interested. Subjects will be counseled not to have vaginal intercourse or insert anything into their vagina from the 72 hours prior to the first transplant dose until 72 hours after the second transplant dose.
- Review eligibility and understand/see applicator
- Obtain informed consent
- Height, weight measurements
- Subjects will be given information about how to perform vaginal swab collections (see vaginal swab collection document)
- Physical exam
- Pelvic exam
- Screening labs: Complete blood cell count w/ differential, comprehensive metabolic panel, Pap/HPV (human papillomavirus) testing, gonorrhea, chlamydia, trichomonas testing. HIV, Hepatitis B&C, Herpes.
- Urine pregnancy test
- Behavior and sexual assessment
Visit 2: Baseline, Week 1 (occurs immediately prior to menses)
- Self-Administered Vaginal Swab and soft cup collection
- Blood draw
- Pelvic Exam: cervical swabs, cytobrush
- Symptom and Sexual Behavior Assessment
- Assignment into study groups using block randomization
- Subjects will be given 7-day course of: Metronidazole 500mg PO every 12 hours
Visit 3: First Transplant Administration, Week 2
- Self-collected Vaginal Swab and soft cup collection
- Pelvic Exam: VMT/placebo Administration
- Symptom and Sexual Behavior Assessment
Visit 4: Second Transplant Administration, Week 2
- Self-Administered Vaginal Swab
- Pelvic Exam: VMT/Placebo Administration
- Symptom and Sexual Behavior Assessment
Visits 5-10: Post-transplant follow ups, Weeks 3, 5, 7, 11, 15, 27
- Blood draw (visit 7 only)
- Self-Administered Vaginal Swab
- Self-Administered soft cup collection (visit 5, 7 & 9)
- Symptom and Sexual Behavior Assessment
- Pelvic Exam: cervical swabs, cytobrush (visits 7 & 9)
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Doug Kwon, MD, PhD
- Phone Number: 857-268-7009
- Email: dkwon@mgh.harvard.edu
Study Locations
-
-
Massachusetts
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Boston, Massachusetts, United States, 02114
- Recruiting
- Massachusetts General Hospital
-
Contact:
- Caroline Mitchell, MD, MPH
- Phone Number: 617-724-2182
- Email: caroline.mitchell@mgh.harvard.edu
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Principal Investigator:
- Caroline Mitchell, MD, MPH
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Premenopausal women, 18- 50 years old
- Abnormal Nugent score: > 3
- History of recurrent bacterial vaginosis (BV) (3 or more documented episodes in past 12 months)
If participating in sexual activity that could lead to pregnancy, study participants must agree to use an effective contraceptive while actively participating in the protocol. At least one of the following methods MUST be used:
- Condoms (male or female), with or without a spermicidal agent
- Intrauterine device (IUD)
- Hormonal contraceptive (including oral pills, vaginal ring, implant, injection)
Exclusion Criteria:
History of clinically significant vaginal, cervical, or uterine disease including but not limited to: cancer of the female reproductive tract, prior hysterectomy, high grade cervical dysplasia (CIN III), or diagnosed with cervicovaginal infection (with the exception of bacterial vaginosis) within the 30 days prior to the procedure.
- Allergy to metronidazole
- Use of investigational therapies or investigational vaccines within 90 days prior to study entry
- Use of any immunomodulatory agents within 30 days prior to study enrollment. Subject taking any of the following medications: systemic steroids (inhaled or nasal steroid therapy is permitted), interleukins, systemic interferons (e.g. local injection of interferon alpha for treatment of HPV is permitted) or systemic chemotherapy.
- History of coronary artery disease, myocardial infarction, COPD, chronic renal failure, decompensated cirrhosis, or any other condition that in the opinion of the investigator will compromise ability to participate in the study.
- History of abnormal pap smear within 12 months
- Insertion of levonorgestrel-containing IUD within 3 months prior to study entry
- Either breastfeeding or pregnant within 24 weeks prior to study entry
- Use of probiotics and prebiotics (supplements and products, oral or vaginal) within 30 days of the study. (NOTE: Oral yogurt with live cultures is allowed.)
- Routine use of oral antibiotics i.e. daily use for acne, Hidradenitis suppurativa, or regular use for post-coital urinary tract infection prophylaxis within the past 30 days.
- Taken non-metronidazole antibiotics in last 30 days
- BMI > 40
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Vaginal microbiome transplant
Women in this group will be randomized to receive two doses of vaginal fluid from a healthy donor
|
Vaginal fluid from healthy donors
500mg oral metronidazole twice daily for 7 days
|
Placebo Comparator: Saline placebo
Women in this group will be randomized to receive two doses of sterile saline
|
500mg oral metronidazole twice daily for 7 days
700 uL of sterile saline placed in the vagina as a placebo intervention.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Presence of Lactobacillus-dominant microbiome
Time Frame: 5 weeks after intervention
|
Lactobacillus dominant = relative abundance of Lactobacillus in the vaginal microbial community > 50%
|
5 weeks after intervention
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Presence of Lactobacillus-dominant microbiome
Time Frame: 1, 3, 7 weeks, 4 and 6 months after intervention
|
Characterization of the vaginal microbial community using 16S rRNA sequencing
|
1, 3, 7 weeks, 4 and 6 months after intervention
|
Number of women reporting adverse events
Time Frame: 1, 3, 5, 7 weeks, 4 and 6 months after intervention
|
Report of adverse events
|
1, 3, 5, 7 weeks, 4 and 6 months after intervention
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Doug Kwon, MD, PhD, Massachusetts General Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Vaginal Diseases
- Vaginitis
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Vaginosis, Bacterial
- Anti-Infective Agents
- Anti-Bacterial Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Metronidazole
Other Study ID Numbers
- 2019P001543
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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