MOTIF@FRESH: Modifying Organisms Transvaginally in Females @ FRESH (MOTIF@FRESH)
研究概览
地位
详细说明
The proposed randomized, double-blinded, placebo-controlled trial is to evaluate the safety of vaginal microbiota transplantation (VMT) in women with recurrent bacterial vaginosis (BV). The study is based in South Africa, at the FRESH (Females Rising through Education, Support, and Health) Clinical Research Site (CRS) located in the Umlazi Township of Durban. The aim of the trial is to assess the ability of antibiotic treatment plus VMT to establish a Lactobacillus-dominant vaginal community. 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 (also known as Donors) using a disposable menstrual cup.
Donors are defined as participants with Nugent scores <4. Over a 16-week period, donors will provide vaginal fluid via softcups (referred to as "donations"). All donations will undergo extensive testing for sexually transmitted infections (STIs) and other infections. Donations that test negative for specified infections will be processed to generate vaginal microbial transplantation (VMT) doses for recipients.
Recipients are defined as participants with Nugent scores ≥4. Because the HPV vaccine is not routinely administered in South Africa, all recipients without documented proof of prior HPV vaccination will receive the HPV vaccine at least 30 days prior to the intervention. The intervention includes the standard of care for bacterial vaginosis in both the U.S. and South Africa: oral metronidazole (MTZ), administered twice daily for seven days. Following completion of the MTZ course, recipients will receive three VMT doses administered over approximately 1.5 weeks. Recipients will be randomized in a 2:1 ratio to receive either VMT or placebo and will be followed for six months post-intervention.
研究类型
注册 (估计的)
阶段
- 阶段2
联系人和位置
学习联系方式
- 姓名：Sarah M Eisa, MPH
- 电话号码：551-689-4016
- 邮箱：seisa@mgh.harvard.edu
研究联系人备份
- 姓名：Eyerusalem T Alemu, BA
- 电话号码：619-522-4661
- 邮箱：ealemu@mgh.harvard.edu
学习地点
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Durban、南非
- FRESH Clinic
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接触：
- Thembelihle Dlamini
- 电话号码：+27 73 318 9320
- 邮箱：lihle.fresh@ragoninsa.org
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接触：
- Sooseela V Pillay
- 电话号码：+27 31- 9060394
- 邮箱：vanessa.fresh@ragoninsa.org
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首席研究员：
- Rosie Mngqbisa, MBChB, MPH
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副研究员：
- Funidiswe Chonco, MD
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副研究员：
- Siphesihle R Ngcobo, MD
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首席研究员：
- Thumbi Ndung'u, PhD
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参与标准
资格标准
适合学习的年龄
- 成人
接受健康志愿者
描述
Inclusion Criteria:
- Premenopausal females between 18 to 25 years of age who are enrolled in the FRESH study
- Nugent score ≥ 4
- Confirmation of use of effective contraceptive method by all study recipient participants (referred to as recipients) of child-bearing potential, which includes use of at least one of the following: Hormonal method, such as birth control pills, patches, injections, vaginal rings, or implants; Barrier method, such as a condom or diaphragm used with a spermicide (a foam, cream, or gel that kills sperm); Intrauterine device (IUD) - non-levonorgestrel containing
- Ability and willingness to give written informed consent.
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 or yeast) within the 30 days prior to the procedure
- Allergy to metronidazole
- Use of investigational therapies or investigational vaccines within 90 days prior to study screening
- Has not received the HPV vaccine and is not willing to be vaccinated
- Metabolic syndrome, e.g. diabetes, pre-diabetes, glucose intolerance
- Use of any immunomodulatory agents within 30 days prior to study enrollment
- Participants taking any of the following medications: systemic steroids (inhaled or nasal steroid therapy is permitted), interleukins, systemic interferons, 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
- Pap smear result of LSIL, HSIL, AGUS
- Insertion of levonorgestrel-containing IUD within 90 days prior to study enrollment
- Either breastfeeding, pregnant, or trying to conceive within 24 weeks prior to study enrollment; or becomes pregnant during study period
Use of probiotics and prebiotics (supplements and products, oral or vaginal) within 30 days of the study
- NOTE: Oral yogurt with live cultures and fermented foods are allowed.
- Routine use of oral antibiotics i.e., daily use for acne, Hiradenitis suppurativa, or regular use for post-coital urinary tract infection prophylaxis within the past 30 days
- Taken non-metronidazole antibiotics in last 30 days
- Taken metronidazole within the last 2 weeks
- BMI > 40
Positive for any of the STIs listed below or on treatment for any of them.
- Neisseria gonorrhoeae
- Chlamydia trachomatis
- HIV
- Trichomonas vaginalis
- Syphilis
- Mycoplasma genitalium
- Currently employed at, or professionally affiliated with the FRESH clinical research site, UKZN's HIV Pathogenesis Program (HPP), or the Ragon Institute of Mass General Brigham, MIT and Harvard (referred to as "the Ragon/MGH" in this document).
- Screens positive for TB by symptomatic questionnaire
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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安慰剂比较：Recipient: Placebo
Women in this group will be randomized to receive three doses of sterile saline solution after completing a full course of MTZ
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Metronidazole 400 mg PO every 12 hours for 7 days is the concomitant medication.
This antibiotic course is the standard Bacterial Vaginosis (BV) treatment which effectively eliminates microbes associated with BV for a limited time.
1mL of sterile saline solution
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有源比较器：Recipient: Vaginal Microbiome Transplantation (VMT)
Women in this group will be randomized to receive three doses of VMT after completing a full course of MTZ
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Metronidazole 400 mg PO every 12 hours for 7 days is the concomitant medication.
This antibiotic course is the standard Bacterial Vaginosis (BV) treatment which effectively eliminates microbes associated with BV for a limited time.
Vaginal fluid from healthy donors
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Evaluate the safety of VMT
大体时间：for 23 weeks after intervention
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The primary outcome of the study is to evaluate if VMT increases the proportion of women with a Lactobacillus crispatus-dominant microbiota at any time within the 4 weeks after the first dose as measured by sequencing of the microbial community where Lactobacillus crispatus make up > 50% of detected microbes.
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for 23 weeks after intervention
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Determine whether VMT will result in a durable change in vaginal microbiota
大体时间：2, 12, and 24 weeks after intervention
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Secondary outcome will measure Lactobacillus crispatus dominance across follow-up weeks.
The hypothesis is that antibiotic plus VMT therapy will increase the proportion of women with a Lactobacillus crispatus-dominant microbiota from 5-10% to 50-60%.
The safety, toxicity, and tolerability of VMT will also be assessed via a) follow up pelvic assessments to assess for rash, irritation or infection calls, b) patient symptom questionnaires to assess self-reported symptoms of vulvovaginal discomfort, and c) adverse event reporting.
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2, 12, and 24 weeks after intervention
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Characterize the host clinical and subclinical mucosal inflammatory response before and after VMT
大体时间：24 weeks after intervention
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Additional secondary, exploratory analyses will be done to evaluate mechanisms for increased Lactobacillus prevalence, or lack thereof.
This will include measuring proportions of individual Lactobacillus species (e.g., L. crispatus, L. iners, L. jensenii, L. gasseri), assessing vaginal microbial community type, microbial community diversity measures, individual taxa associated with treatment group, and host mucosal inflammatory immune response.
(e.g., vaginal concentration of IL1beta, IL1alpha, IL1RA, IL6, IL8, TNFa, IFNg)
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24 weeks after intervention
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合作者和调查者
赞助
调查人员
- 首席研究员：Caroline Mitchell, MD, MPH、Massachusetts General Hospital
- 首席研究员：Douglas S Kwon, MD, PhD、Ragon Institute of MGB, MIT, and Harvard
- 首席研究员：Krista Dong, MD、Ragon Institute of MGB, MIT, and Harvard
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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