Intravaginal LACTIN-V for Prevention of Recurrent Urinary Tract Infections
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Incidence of Urinary Tract Infection
研究概览
简要总结
Recurrent urinary tract infections (RUTIS) continue to be a major health problem in women and are now complicated by increasing antibiotic resistance. New preventive approaches are needed. Because most women with RUTI lack the normal protective Lactobacillus (LB) in their vaginal flora, we hypothesized that restoration of LB would reduce RUTIS. In this trail, women with recent UTI are randomized to receive either LB or placebo vaginal capsules and are followed for side effects, for colonization with LB and for occurrence of RUTI over hte next four months.
详细描述
Purpose: The purpose of this study is to evaluate the safety of the vaginal suppository LACTIN-V (Lactobacillus crispatus CTV-05) as well as the efficacy of LACTIN-V use in preventing recurrent urinary tract infections (RUTI) in women. Study subjects will include pre-menopausal women with a history of frequent RUTI. As part of this study, we will also evaluate growth of lactobacilli and urinary tract infection(UTI)-causing bacteria in the vaginas of women following use of LACTIN-V.
Rationale: LACTIN-V is composed of L. crispatus. L. crispatus is a bacteria found to grow naturally in the vaginas of healthy women. It is felt to be important in preventing vaginal infection and UTI. With regard to prevention of UTI, L. crispatus is thought to prevent the growth of UTI-causing bacteria (such as E. coli) in the vagina, and so prevent these UTI-causing bacteria from being able to enter the female urethra and cause infection in the bladder (cystitis). There is epidemiologic evidence to support this prevention mechanism, as absence of L. crispatus and related lactobacilli from the vagina has been associated with vaginal E. coli growth and with UTI. Scientific evidence supports the ability of lactobacilli to prevent vaginal E. coli growth by out-competing E. coli in vaginal colonization, and through the production of toxins such as lactic acid, hydrogen peroxide, and bacteriocins.
LACTIN-V contains a specific strain of L. crispatus, CTV-05, which was isolated from the vagina of a healthy woman. It was prepared as a vaginal suppository with the purpose of restoring growth of healthy L. crispatus in the vaginas of women who experience frequent RUTI. As indicated above, these women often have a deficiency of healthy vaginal lactobacilli growth, and therefore may not experience the protective function of these natural organisms. It is hoped that use of LACTIN-V will lead to vaginal growth of protective lactobacilli in these women wich will, in turn, prevent the vaginal growth of E. coli and other UTI-causing bacteria. Phase 1 and 2 studies of LACTIN-V to date have shown this "probiotic" to be safe and well tolerated.
The impetus for this study is the urgent need for non-antibiotic strategies to prevent UTI. UTI is one of the most common bacterial infections. It leads to substantial morbidity and health care costs. Frequent use of antibiotics for treatment of and prophylaxis against UTI is contributing to the prevalence of antibiotic resistant bacteria, which are also making it more difficult to treat UTI. Therefore, the potential advantage of LACTIN-V is that it is a natural product that may prevent UTI without the use of antibiotics. If it proves to be efficacious, it could decrease the morbidity and health care costs associated with UTI as well as decrease overall antibiotic use and the corresponding prevalence of antibiotic resistance among UTI-causing bacteria.
Primary Objective: The primary objective is to evaluate the safety of LACTIN-V, compared to placebo, in pre-menopausal women with recurrent uncomplicated UTI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •pre-menopausal woman aged 18-40 years
- •current symptomatic uncomplicated cystitis
- •cystitis is treated with trimethoprim-sulfamethoxazole (TMP-SMX)
- •completion of screening procedures
- •negative screening monolayer Pap smear or hysterectomy
- •history of at least two prior symptomatic UTI's treated within the past 12 months or one pior symptomatic UTI treated in the past six months
- •agree to return for the Randomization Visit (Visit 2)
- •regular menstrual cycles or amenorrheic due to use of a long acting progestin, continuous use of oral contraceptives or hysterectomy
- •willing to insert vaginal capsules without an applicator
- •capable of providing informed consent
- •able to read and understand English
- •agree to abstain from self-medication with antibiotics for UTI symptoms
- •agree to abstain from antibiotic prophylaxis for recurrent UTI
- •agree to abstain from the use of any other intra-vaginal product
- •agree to abstain from sexual intercourse for 24 hours after capsule insertion
- •agree to not use tampons for 24 hours after capsule insertion
- •agree to use an adequate method of birth control
排除标准
- •complicated cystitis or uncomplicated pyelonephritis.
- •cystitis at Visit 1 not treated with TMP-SMX
- •uropathogen resistant to TMP-SMX isolated at Visit 1 and persistent symptoms at Visit 2 or failure to achieve a significant reduction in urine wbc count at Visit 2
- •vaginal or cervical infection, currently or within the past 21 days, with bacterial vaginosis (treated, symptomatic infection), Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis or Herpes Simplex
- •symptomatic bacterial vaginosis at Visit 1
- •high risk for sexually transmitted diseases and/or HIV, including:
- •diagnosis of N. gonorrhoeae, C. trachomatis or T. vaginalis on two or more occasions during the previous six months;
- •sexual intercourse with a homosexual/bisexual male in the last 10 years;
- •sexual intercourse with an injection drug user or sex worker in the last 10 years; or
- •shared needles for injected drugs in the last 10 years.
- •chronic vaginal, urinary or pelvic symptoms not attributable to UTI
- •recurrent bacterial vaginosis (three or more symptomatic, treated infections in the prior 12 months)
- •pregnancy or within two months of last pregnancy
- •lactation
- •antibiotic therapy fewer than three days prior to Randomization Visit
- •antifungal therapy fewer than seven days prior to the Randomization Visit
- •Antibiotics planned within four months
- •abnormal Pap smear requiring a procedure for diagnosis or treatment in the past 12 months
- •use of CTV-05 within one year of the Randomization Visit
- •menopause
- •use of a NuvaRing planned during the course of the study
- •any significant disease or acute illness that in the Investigator's assessment could complicate the evaluation
- •known HIV infection
- •immunosuppressive drug within 60 days
- •known allergy to any component of LACTIN-V or the placebo capsule
- •unavailable for follow-up visits
- •drug or alcohol abuse within past two years
- •any social or medical condition that, in the opinion of the Investigator, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
研究组 & 干预措施
Lactin-V
Vaginal capsule containing Lactobacillus crispatus in high concentration. Self-administered once daily for 5 days during the 1st week. Self-administered once weekly for 10 weeks.
干预措施: Lactin-V (Drug)
Placebo
Vaginal capsule - placebo. Self-administered once daily for 5 days during the 1st week. Self-administered once weekly for 10 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Urinary Tract Infection
时间窗: 10 weeks
Recurrent urinary tract infection after initiation of intervention. Culture-confirmed to contain uropathogen.
次要结局
- Incidence of Vaginal Discharge(4 months)
研究者
Ann Stapleton
Professor
University of Washington