MOTIF@FRESH: Modifying Organisms Transvaginally in Females @ FRESH (MOTIF@FRESH)
Обзор исследования
Статус
Подробное описание
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.
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 2
Контакты и местонахождение
Контакты исследования
- Имя: Sarah M Eisa, MPH
- Номер телефона: 551-689-4016
- Электронная почта: seisa@mgh.harvard.edu
Учебное резервное копирование контактов
- Имя: Eyerusalem T Alemu, BA
- Номер телефона: 619-522-4661
- Электронная почта: ealemu@mgh.harvard.edu
Места учебы
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Durban, Южная Африка
- FRESH Clinic
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Контакт:
- Thembelihle Dlamini
- Номер телефона: +27 73 318 9320
- Электронная почта: lihle.fresh@ragoninsa.org
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Контакт:
- Sooseela V Pillay
- Номер телефона: +27 31- 9060394
- Электронная почта: vanessa.fresh@ragoninsa.org
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Главный следователь:
- Rosie Mngqbisa, MBChB, MPH
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Младший исследователь:
- Funidiswe Chonco, MD
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Младший исследователь:
- Siphesihle R Ngcobo, MD
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Главный следователь:
- Thumbi Ndung'u, PhD
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
Принимает здоровых добровольцев
Описание
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
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Четырехместный
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Плацебо Компаратор: 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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Активный компаратор: 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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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Evaluate the safety of VMT
Временное ограничение: 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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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Determine whether VMT will result in a durable change in vaginal microbiota
Временное ограничение: 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
Временное ограничение: 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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Соавторы и исследователи
Спонсор
Следователи
- Главный следователь: Caroline Mitchell, MD, MPH, Massachusetts General Hospital
- Главный следователь: Douglas S Kwon, MD, PhD, Ragon Institute of MGB, MIT, and Harvard
- Главный следователь: Krista Dong, MD, Ragon Institute of MGB, MIT, and Harvard
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
- Урогенитальные заболевания
- Генитальные заболевания
- Женские урогенитальные заболевания
- Женские мочеполовые заболевания и осложнения беременности
- Инфекции
- Заболевания половых органов, Женский
- Бактериальные инфекции
- Бактериальные инфекции и микозы
- Вагинит
- Вагинальные заболевания
- Вагиноз, Бактериальный
- Органические химические вещества
- Гетероциклические соединения, 1-кольцо
- Гетероциклические соединения
- Азолы
- Имидазолы
- Нитроимидазолы
- Нитро -соединения
- Метронидазол
Другие идентификационные номера исследования
- 2026P000260
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
продукт, произведенный в США и экспортированный из США.
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