Bacterial Composition and Recurrent Cystitis in Postmenopausal Women After Treatment With Lactobacilli.

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about the effect on the bacterial composition in the microbiome (the body's own bacteria) of urine, vagina and faeces after treatment with lactobacilli (lactobacilli's are a part of the microbiome), and its influence on repeated cystitis in postmenopausal women. The main questions it aims to answer are: Does treatment with lactobacilli change the composition of the urine microbiome in postmenopausal women? Does treatment with lactobacilli prevent repeated cystitis in postmenopausal women? Participants will be followed for 6 months. They will for 3 months receive a look-alike substance that contains no active drug and for the other 3 months tablets with lactobacilli. A computer program will decide what treatment the participant will begin with, and after 3 months she will be receiving the tablets, she did not get first. This way all participants receive both type of tablets and can be their own control. What type of tablet the participants is taking is unknown to both clinical staff and participants. The participants will come to the hospital for start-up, and every 1,5 moths for the next 6 months. They deliver faeces sample urine tests vaginal swab each time they are seen. When entering the study, they also complete health care questions on medication, earlier surgery, alcohol, tobacco, childbirths, weight, height etc. They make a drinking and voiding diary 3 times over the 6 months. When the study is over, alle the samples of faeces, urine and the vaginal swab will undergo analyzation for the bacterial composition in the microbiome, and differences in the microbiome when taking lactobacilli or not will be examined. The urine sample is controlled for bacteria known to give cystitis, and the influence on repeated cystitis will also be examined.

Official Title
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The Effect on Bacterial Composition in Urine, Vagina and Faces After Treatment With Lactobacilli and Its Influence on Recurrent Cystitis in Postmenopausal Women.

Conditions
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Cystitis Recurrent, Lactobacillus Infection

Intervention / Treatment
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* Dietary Supplement: FEMIDUR®
* Other: Placebo Z Cap V-3 Pla


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: postmenopausal women if hysterectomy before menopause, then age of >60 years verified diagnose of recurrent cystitis. (two in 6 months or 3 in a year, verified by cultivation) able to speak and write Danish Exclusion Criteria: vaginal prolapse with symptoms residual urine over 150 ml bladder diseases profylactic antibiotics probiotics bladder cancer genital cancer.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: double blinded prospective, randomized cross-over study. Taking place over 6 months with 5 clinical visits.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>As it is blinded, no one knows which arm participants enter. After 3 months the other arm is entered. | Other: Placebo Z Cap V-3 Pla<br>* Consist mainly of maltodextrin. One tablet a day.<br>|
| Active Comparator: Femidur<br>As it is blinded, no one knows which arm participants enter. After 3 months the other arm is entered. | Dietary Supplement: FEMIDUR®<br>* Femidur® consist of 2 vaginal lactobacillis; Lactobacillus rhamnosus GR-1® and Lactobacillus reuteri RC-14®. One tablet a day. Placebo Z Cap V-3 Pla; mainly maltodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the urine microbiome among postmenopausal women when treated with lactobacillis | The micobiom will be analysed by 16s rRNA sequencing. | after study completion, an average of 1.5 year | 
| The change in the urine microbiome among postmenopausal women when treated with lactobacillis | Operational taxonomic unit (OTU) richness | after study completion, an average of 1.5 year | 
| The change in the urine microbiome among postmenopausal women when treated with lactobacillis | Shannon Index, as expression for the alpha diversity | after study completion, an average of 1.5 year | 
| The change in the urine microbiome among postmenopausal women when treated with lactobacillis | Beta diversity by means of PCA plots | after study completion, an average of 1.5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| episodes of UTI | in numbers over time. | after study completion, an average of 2 months | 
| changes in vaginal micobiome | The micobiom will be analysed by 16s rRNA sequencing. | after study completion, an average of 1.5 year | 
| changes in vaginal micobiome | Operational taxonomic unit (OTU) richness | after study completion, an average of 1.5 year | 
| changes in vaginal micobiome | Shannon Index, as expression for the alpha diversity | after study completion, an average of 1.5 year | 
| changes in vaginal micobiome | Beta diversity by means of PCA plots | after study completion, an average of 1.5 year | 
| Changes in fecal microbiome | The micobiom will be analysed by 16s rRNA sequencing. | after study completion, an average of 1.5 year | 
| Changes in fecal microbiome | Operational taxonomic unit (OTU) richness | after study completion, an average of 1.5 year | 
| Changes in fecal microbiome | Shannon Index, as expression for the alpha diversity | after study completion, an average of 1.5 year | 
| Changes in fecal microbiome | Beta diversity by means of PCA plots | after study completion, an average of 1.5 year |