The Association Between the Transfer of Lactobacilli From the Gastrointestinal Tract to the Vagina and the Prevention / Eradication of Abnormal Vaginal Flora in High Risk Pregnancies

Study Overview
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Brief Summary
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Pregnant women at high risk for preterm labor from at least 13 weeks of gestation will be tested to detect abnormal vaginal flora (AVF) or its severe form - bacterial vaginosis (BV) by taking vaginal smear. Treatment will be given according to the results.

Detailed Description
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Pregnant women at high risk for preterm labor from at least 13 weeks of gestation will be tested to detect AVF/BV by taking vaginal smear. Diagnosis will be according to the Nugent score criteria. Treatment will be given according to the results: Patient with a positive smear for AVF- patients tested positive will be treated with either clindamycin or metronidazole. Following treatment another smear will be taken according to which the patients will be divided into 2 research groups: (1) Assessing the effectiveness of probiotic formula to prevent AVF re-infection (secondary infection) - this group includes patients with normal vaginal flora following antibiotic administration. (2) Assessing the effectiveness of probiotic formula to eradicate AVF - this group includes patients with persistent AVF following antibiotic administration (first and second line). In each group the patients will be divided into a research group which will receive the probiotic formula UREX PLUS (containing L. rhamnosus GR-1and L. reuteri RC-14) and a control group which will receive a placebo twice a day until 36.6 weeks of gestation. Patient with a negative smear for AVF - in those patients the effectiveness of probiotic formula will be tested for primary prevention. These patients will be divided into a research group which will receive the probiotic formula UREX PLUS and a control group which will receive a placebo twice a day until 36.6 weeks of gestation. Finally, the colonization of lactobacilli in the vaginal flora will be examined by dividing patients with normal vaginal flora into one group receiving a probiotic capsule containing L. rhamnosus GR-1 and L. reuteri RC-14 twice a day for 2 months and a second group without intervention. After two months the group receiving probiotic capsule will receive no treatment and the second group will receive probiotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14 twice a day for 2 months.

Official Title
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The Association Between the Transfer of Lactobacilli From the Gastrointestinal Tract to the Vagina and the Prevention / Eradication of Abnormal Vaginal Flora in High Risk Pregnancies

Conditions
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Pregnancy

Intervention / Treatment
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* Dietary Supplement: Urex Plus
* Other: Placebo
* Dietary Supplement: Probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pregnant women from at least 13 weeks of gestation with a risk factor for preterm labor Exclusion Criteria: Women with preterm premature rupture of the membranes Immunocompromised women Planned elective preterm birth for reasons other than preterm premature rupture of membranes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary prevention - Urex Plus<br>Patients with Normal vaginal flora in the experimental arm will be treated with UREX PLUS | Dietary Supplement: Urex Plus<br>* Probiotic<br>|
| Placebo Comparator: Primary prevention - Placebo<br>Patients with Normal vaginal flora in the Placebo arm will be treated with a capsule without active ingredient | Other: Placebo<br>* capsule without active ingredient<br>|
| Experimental: Secondary prevention - Urex Plus<br>Patients with abnormal vaginal flora in the experimental arm will be treated with antibiotic (either clindamycin, metronidazole or both if one was not effective), Once AVF/BV was eradicated, the patient will be given UREX PLUS | Dietary Supplement: Urex Plus<br>* Probiotic<br>|
| Placebo Comparator: Secondary prevention - Placebo<br>Patients with abnormal vaginal flora in the Placebo arm will be treated with antibiotic (either clindamycin, metronidazole or both if one was not effective), Once AVF/BV was eradicated, the patient will be given placebo without active ingredient | Other: Placebo<br>* capsule without active ingredient<br>|
| Experimental: Eradication - Urex Plus<br>Patients with persistent abnormal vaginal flora following treatment with clindamycin and metronidazole in the experimental arm will be treated with UREX PLUS | Dietary Supplement: Urex Plus<br>* Probiotic<br>|
| Placebo Comparator: Eradication - Placebo<br>Patients with persistent abnormal vaginal flora following treatment with clindamycin and metronidazole in the placebo arm will be treated with placebo without active ingredient | Other: Placebo<br>* capsule without active ingredient<br>|
| Other: Lactobacilli transfer - probiotic capsule<br>Patients with Normal vaginal flora will be treated with a probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14 for two months afterwhich they will receive no treatment for additional two months. Lactobacili colonization in the vaginal flora will be tested | Dietary Supplement: Probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14<br> <br> |
| Other: Lactobacilli transfer - probiotic capsule after 2 months<br>Patients with Normal vaginal flora will be followed for two months without intervention afterwhich they will receive a probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14 for two months. Lactobacili colonization in the vaginal flora will be tested. | Dietary Supplement: Probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount of lactobacilli in the vaginal | Lactobacilli culture will be made from a vaginal specimen. The pattern of bacterial growth will be used for a semi-quantitative interpretation in a scale of 0-no vaginal colonization to 4-substantial colonization. | once a month until week 36.6 of labor | 
| The rate of women with normal vaginal flora at enrollment, who developed AVF/BV during the study period |  | From date of randomization until the date of first documented episode or until delivery (around 4 months) | 
| The rate of women with AVF/BV at enrollment whose infection was eradicated following antibiotics, who developed AVF/BV during the study period |  | From date of randomization until the date of first documented episode or until delivery (around 4 months) | 
| The rate of women with AVF/BV at enrollment whose infection was not eradicated following antibiotics, who restored the normal vaginal flora during the study period |  | Until delivery (around 4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of time from the beginning of the study until an episode of AVF/BV |  | From date of randomization until the date of first documented episode or until delivery (around 4 months) | 
| The number of episodes of BV/AVF during pregnancy |  | Until delivery (around 4 months) | 
| The rate of women, who suffer from obstetrical outcomes(preterm labor, intrauterine growth restriction, preterm premature rupture of membranes, chorioamnionitis, post-partum fever, post-partum endometritis, neonatal sepsis and neonatal complications) |  | Until delivery (around 4 months) | 
| The rate and type of adverse effects in the probiotic versus placebo groups |  | Until delivery (around 4 months) | 
| Number of urinary tract infections during the study period |  | Until delivery (around 4 months) |