Lactobacillus Probiotic for Prevention of UTI

Study Overview
=================
Brief Summary
-----------------
The purpose of this research is to see whether LACTIN-V (Lactobacillus crispatus CTV-05) is an effective method of preventing recurrent urinary tract infections (UTI's) and to learn the side effects of LACTIN-V. LACTIN-V is a vaginal applicator that contains Lactobacillus crispatus, an organism found naturally in the vaginas of healthy women. Lactobacillus bacteria are thought to help prevent other bacteria such as E. coli from causing UTI's. This is a double blind study comparing active product to a placebo (inactive vaginal applicator without any medicine).

Detailed Description
-----------------
The initial study visit will take about one hour. Participants will read, discuss and sign a consent form. Investigators will have the patient collect a mid-stream urine sample which will be sent to the research lab to confirm the participant has a urinary tract infection (UTI). Participants will than be given Macrobid twice a day for five days for UTI treatment. If the results of the screening show eligibility for this study, investigators will ask the participant to return to the clinic within 3-10 day after completing UTI treatment for a randomization visit (v1). Visit 1 (Randomization Visit): During this visit, the participant will be asked about any urinary or vaginal symptoms. The participant will be asked to provide a urine sample to see if the UTI has resolved and for a pregnancy test. The participant will have a physical exam including a pelvic and speculum exam. A study nurse practitioner will collect vaginal specimens to test for vaginal bacteria and vaginal infections. Next, the participant will be randomly assigned (like flipping a coin) to use LACTIN-V or placebo vaginal applicators. The participant will not be told which product is being used, and the researchers will not know until the end of the study. The participant will not be able to tell which one is being used. Each LACTIN-V applicator contains Lactobacillus crispatus CTV-O5 and other preservatives. Each placebo suppository contains other preservatives. Participants will be instructed how to use the applicators. The participant will also be given written instructions on how to use, store, and handle the applicators, and a diary to record when the participant uses the applicators and any symptoms that may happen during the study. (Participants will be given 15 applicators).The participant will insert 15 applicators during this study. The applicators are to be used daily for five days during the first week and then once per week for 10 weeks starting the second week. To insert an applicator, the participant will hold one applicator between a thumb and finger (like a tampon),insert the applicator into the opening of the vagina, and then push the applicator plunger. The participant will insert the first applicator in the clinic during this visit. The participant will be asked not to have sexual intercourse or use tampons for 24 hours after inserting an applicator. The participant will also be asked not to use spermicidal vaginal products. The participant will also be asked not to use other vaginal products such as creams, gels, foams, sponges, lubricants, or douches or take antibiotics for a UTI during this study unless the participants doctor prescribes it. The visit will take 30-60 minutes. Visits 2-6 The participant will then be asked to return to the Hall Health clinic in 2 weeks and then once a month for the next 4 months, after the randomization visit. During these visits a study nurse practitioner will ask about any side-effects that may have occurred from the study drug or placebo. The study nurse practitioner will also ask if the participant had any UTI's since the last visit. The participant will be asked to give a urine sample for culture. The participant will also have a physical exam, and vaginal tests for infection, lactobacillus (including lactobacillus from LACTIN-V) and E. coli. A speculum exam will only be done at v1 and the last visit unless the participant has symptoms of a vaginal infection. The last visit will include a urine pregnancy test. These visits will take 30 minutes. Other Visits: If the participant has a UTI or vaginal infection during the study, the participant will be seen at Hall Health for treatment. The participant will be treated with a standard medication at no cost.. If a UTI occurs during the study the participant will continue to use the study applicator on schedule.

Official Title
-----------------
Lactobacillus Probiotic for Prevention of UTI

Conditions
-----------------
Urinary Tract Infections (UTI's)

Intervention / Treatment
-----------------
* Drug: Lactobacillus crispatus CTV-05
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: pre-menopausal women present with an acute, uncomplicated, culture confirmed UTI, defined as dysuria, urgency and/or frequency at least one previous medically diagnosed UTI in past 12 months using a reliable method of birth control ie: history of tubal ligation, male partner with vasectomy, steroidal contraception, Nuva-Ring, IUD, use of non spermicidal condoms or abstinence. can provide written consent can understand and read English Exclusion Criteria: history of urogenital infection within the past 30 days, including: UTI, medically diagnosed vaginitis current symptoms suggestive of pyelonephritis (fever>100.4, flank pain of costovertebral angle tenderness, nausea and vomiting history of functional or anatomic urologic abnormalities, urologic surgery of chronic urinary catheterization history of pyelonephritis within the past 6 months diagnosis of N. gonorrhoeae, C. trachomatis or T. vaginalis on two or more occasions during previous six months known HIV infection of seropositivity investigational drug use within 30 days of enrollment visit or current participation in another clinical trial diabetes, other significant medical problem or intercurrent acute illness that in the Nurse Practitioner's and/or Principal 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 objective. At the randomization visit, has any of the following findings on pelvic or other physical examination: unable to visualize cervix clinically significant abnormalities, such as inflammation, erosion and/or petechiae (bleeding under the skin) of external genitalia, vaginal or cervix on visual examination clinically significant tenderness on bimanual examination during the pelvic examination evidence of vaginitis or a sexually-transmitted disease any diagnosis requiring antibiotics

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Applicator with LACTIN-V Treatment<br>Vaginal applicator containing Lactobacillus crispatus CTV-05 | Drug: Lactobacillus crispatus CTV-05<br>* vaginal applicator with medium containing drug<br>* Other names: Lactin-V;|
| Placebo Comparator: Applicator with Placebo<br>Inactive vaginal applicator without any drug | Drug: Placebo<br>* vaginal applicator with medium containing no drug<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UTI Incidence as Described Below, Over the 16 Week Study Period Following Randomization, in the LACTIN-V Treatment Group (Group A) as Compared to the Placebo Group (Group B). | Symptomatic UTI : Comparison of the number (%) of subjects over the 16-week study period following randomization, with at least one symptomatic UTI (as defined above) in the 2 intervention groups | Week 2-18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parameter of Vaginal Colonization | Lactobacillus crispatus positive (as assessed by repPCR) at Weeks 0,2,6,10,14, and 18 in the Lactin-V group as compared to the placebo group | Weeks 0, 2, 6, 10, 14 and18 |