Role of Oral Lactobacilli on Vaginal Flora of Pregnant Women
Primary Purpose
Bacterial Vaginosis
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Lactobacilli rhamnosus GR-1 and Lactobacilli fermentum RC-14
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Bacterial Vaginosis
Eligibility Criteria
Inclusion Criteria:
- Pregnant women <18 weeks gestational age
- >18 years old and able provide informed consent
- No clinical bacterial vaginosis requiring anti-microbial treatment
- BV Blue test positive on screening
- Planned or probable delivery at UTMB, Galveston
Exclusion Criteria:
- Taking antibiotics or any other microbial at the time of recruitment
- Documented need for cervical cerclage
- Multi fetal pregnancy
- Known aneuploidy or lethal fetal anomalies
- Illicit drug use
Serious maternal medical conditions
- Renal insufficiency with serum creatinine >1.5, known proteinuria >300mg/24 hours or receiving dialysis.
- Chronic liver disease with liver transaminases >2 times the upper limit of the normal range
- Organ transplant recipients.
- Severe pulmonary disorder (such as significant obstructive/restrictive disorder, pulmonary hypertension, cystic fibrosis, and chronic oxygen requirement).
- Severe heart disease (such as cardiomyopathy with decreased left ventricular ejection fraction, obstructive valvular disease, replaced heart valve, uncorrected aortic coarctation or tetrology).
- Established lupus anticoagulant syndrome or antiphospholipid syndrome).
- Diabetes class C and greater
- Chronic conditions requiring medications for control (such as chronic hypertension, SLE, inflammatory bowel disease, and asthma).
- Acquired Immunodeficiency Syndrome or HIV infection without AIDS.
Medical complications of pregnancy
- Pre-eclampsia
- Thrombophilia
- Pregnancy induced hypertension
- Gestational diabetes
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Lactobacilli
Placebo
Arm Description
Lactobacilli rhamnosus GR-1 and Lactobacilli fermentum RC-14 Lactobacilli rhamnosus GR-1 and Lactobacilli fermentum RC-14
Receives placebo
Outcomes
Primary Outcome Measures
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
This number will determine if oral supplementation of lactobacilli is safe and tolerated by pregnant women.
Secondary Outcome Measures
Number of participants with incidence and severity of Bacterial Vaginosis during pregnancy assessing for positive lab results screening for Bacterial Vaginiosis
BV Blue test
Nugent scoring
Amsel clinical criteria
Number of Preterm deliveries
Preterm delivery (<37 weeks gestation)
Measure the inflammatory markers in the vaginal secretions
IL1β
IL6
IL8
TNF-α
GmCSF
Full Information
NCT ID
NCT04638257
First Posted
October 5, 2015
Last Updated
November 19, 2020
Sponsor
The University of Texas Medical Branch, Galveston
1. Study Identification
Unique Protocol Identification Number
NCT04638257
Brief Title
Role of Oral Lactobacilli on Vaginal Flora of Pregnant Women
Official Title
A Phase I, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Effects of Probiotic Lactobacilli on Vaginal Flora of Pregnant Women
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Medical Branch, Galveston
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Bacterial vaginosis (BV) occurs in about 20% of pregnancies and responsible for up to 25% of visits to gynecological clinics. BV is characterized by a shift in vaginal bacterial flora from lactobacilli to pathogenic bacterial flora like Gardnerella and Mycoplasma. Risk factors for the development of BV include douching, use of intrauterine contraceptive devices, new or multiple sexual partners, smoking and African American background.
Detailed Description
Diagnosis of BV based on Amsel's criteria and Nugent's scoring. In Amsel's criteria include: presence of thin vaginal discharge, clue cells, vaginal fluid pH >4.5 and positive whiff test. The Nugent score is derived from gram-stained vaginal smear; yielding a score between 0 - 10. A score of, 4 is normal, 4 - 6 is intermediate and a score >7 represents BV. CDC recommends diagnosis of BV on the presence of >3 Amsel criteria and a Nugent score >7. FDA recommends, verification of BV cure should be conducted 21 - 30 days after the initiation of therapy (absence of Amsel's criteria and Nugent score <4).
Cure rate of BV with conventional anti-microbial agents have been disappointing due to high recurrence rate of BV. Recurrence of BV results in repeated exposure to anti-microbial agents which may lead to emergence of drug-resistance strains & the potential for adverse reactions. This suggests a need for alternative therapeutic measures of BV.
Lactobacilli rhamnosus GR-1 and Lactobacilli fermentum RC-14 are H2O2 producing lactobacilli which are toxic to bacteria causing BV by antagonizing the growth and adhesion of pathologic bacteria causing BV. In non-pregnant women, oral administrations of these strains of lactobacilli are safe, and reduce the risk of BV by restoring predominant lactobacilli, the normal vaginal bacterial flora.
Bacterial vaginosis is associated with increased incidence of preterm delivery. For pregnant women, restoration of lactobacilli in the genital tract could be very important to prevent BV and may lower the risk of preterm labor. At present, the safety, tolerability and efficacy of lactobacilli use during pregnancy is not well known for the fetus and the pregnant women. The investigators plan to do a phase I trial to evaluate the safety, tolerability, and efficacy of oral lactobacilli on vaginal flora of pregnant women and follow up their infants for any side effect up to 6 months of age.
In summary, treatment failure and recurrence of BV following anti-microbial treatment is frustrating. During pregnancy, probiotics may be the next step to treat BV and restore normal vaginal micro flora. But the safety of lactobacilli use during pregnancy is not established. The investigators will do phase I trial to evaluate safety of oral lactobacilli in pregnant women along with their infants up to 6 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacterial Vaginosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lactobacilli
Arm Type
Experimental
Arm Description
Lactobacilli rhamnosus GR-1 and Lactobacilli fermentum RC-14 Lactobacilli rhamnosus GR-1 and Lactobacilli fermentum RC-14
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Receives placebo
Intervention Type
Biological
Intervention Name(s)
Lactobacilli rhamnosus GR-1 and Lactobacilli fermentum RC-14
Intervention Description
Daily oral Lactobacilli starting at =<18 weeks of gestation in singleton pregnancy
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Daily oral placebo starting at =<18 weeks of gestation in singleton pregnancy
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
This number will determine if oral supplementation of lactobacilli is safe and tolerated by pregnant women.
Time Frame
Pregnancy (<18 weeks gestation) for 60 days
Secondary Outcome Measure Information:
Title
Number of participants with incidence and severity of Bacterial Vaginosis during pregnancy assessing for positive lab results screening for Bacterial Vaginiosis
Description
BV Blue test
Nugent scoring
Amsel clinical criteria
Time Frame
baseline up until 8 (after starting the study drug)
Title
Number of Preterm deliveries
Description
Preterm delivery (<37 weeks gestation)
Time Frame
baseline up until 36 weeks gestation
Title
Measure the inflammatory markers in the vaginal secretions
Description
IL1β
IL6
IL8
TNF-α
GmCSF
Time Frame
baseline up until 8 (after starting the study drug)
10. Eligibility
Sex
Female
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pregnant women <18 weeks gestational age
>18 years old and able provide informed consent
No clinical bacterial vaginosis requiring anti-microbial treatment
BV Blue test positive on screening
Planned or probable delivery at UTMB, Galveston
Exclusion Criteria:
Taking antibiotics or any other microbial at the time of recruitment
Documented need for cervical cerclage
Multi fetal pregnancy
Known aneuploidy or lethal fetal anomalies
Illicit drug use
Serious maternal medical conditions
Renal insufficiency with serum creatinine >1.5, known proteinuria >300mg/24 hours or receiving dialysis.
Chronic liver disease with liver transaminases >2 times the upper limit of the normal range
Organ transplant recipients.
Severe pulmonary disorder (such as significant obstructive/restrictive disorder, pulmonary hypertension, cystic fibrosis, and chronic oxygen requirement).
Severe heart disease (such as cardiomyopathy with decreased left ventricular ejection fraction, obstructive valvular disease, replaced heart valve, uncorrected aortic coarctation or tetrology).
Established lupus anticoagulant syndrome or antiphospholipid syndrome).
Diabetes class C and greater
Chronic conditions requiring medications for control (such as chronic hypertension, SLE, inflammatory bowel disease, and asthma).
Acquired Immunodeficiency Syndrome or HIV infection without AIDS.
Medical complications of pregnancy
Pre-eclampsia
Thrombophilia
Pregnancy induced hypertension
Gestational diabetes
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sunil K Jain, MD
Organizational Affiliation
University of Texas Medical Branch at Galveston
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Role of Oral Lactobacilli on Vaginal Flora of Pregnant Women
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