MOTIF@FRESH: Modifying Organisms Transvaginally in Females @ FRESH (MOTIF@FRESH)
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Sarah M Eisa, MPH
- 電話番号：551-689-4016
- メール：seisa@mgh.harvard.edu
研究連絡先のバックアップ
- 名前：Eyerusalem T Alemu, BA
- 電話番号：619-522-4661
- メール：ealemu@mgh.harvard.edu
研究場所
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-
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Durban、南アフリカ
- FRESH Clinic
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コンタクト：
- Thembelihle Dlamini
- 電話番号：+27 73 318 9320
- メール：lihle.fresh@ragoninsa.org
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コンタクト：
- Sooseela V Pillay
- 電話番号：+27 31- 9060394
- メール：vanessa.fresh@ragoninsa.org
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主任研究者：
- Rosie Mngqbisa, MBChB, MPH
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副調査官：
- Funidiswe Chonco, MD
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副調査官：
- Siphesihle R Ngcobo, MD
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主任研究者：
- Thumbi Ndung'u, PhD
-
-
参加基準
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：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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アクティブコンパレータ：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Evaluate the safety of VMT
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Determine whether VMT will result in a durable change in vaginal microbiota
時間枠：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
時間枠：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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協力者と研究者
スポンサー
捜査官
- 主任研究者：Caroline Mitchell, MD, MPH、Massachusetts General Hospital
- 主任研究者：Douglas S Kwon, MD, PhD、Ragon Institute of MGB, MIT, and Harvard
- 主任研究者：Krista Dong, MD、Ragon Institute of MGB, MIT, and Harvard
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 2026P000260
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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