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Red Clover Isoflavones in Postmenopausal Women With Urge Urinary Incontinence and Overactive Bladder

Primary Purpose

Urge Incontinence, Overactive Bladder

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Red Clover Extract (RCE)
Placebo (PL)
Sponsored by
Vendsyssel Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Urge Incontinence focused on measuring Microbiota, Microbiome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Postmenopausal (more than 5 years since last menstruation)
  • Read and understand Danish

Exclusion Criteria:

  • Participants receive treatment with estrogen both oral, transdermal, and topical within three months prior to inclusion in the study
  • Participants take estrogen-like compounds (isoflavones) three months prior to inclusion in the study
  • Participants take prebiotic and/or probiotic supplements within three months prior to study inclusion
  • Receive antibiotics (any) within three months prior to inclusion in the study
  • Recurrent urinary tract infections (defined as ≥ 2 infections in the last six months or ≥ 3 infections during the last year)
  • Acute urinary tract infection defined as positive urine culture and symptoms of acute cystitis
  • Previous or current diseases of the digestive and/or urinary systems evaluated by PI (including, but not limited to inflammatory bowel disease (IBD) and cancer)
  • Current or prior suffering from breast, ovary, and/or endometrial cancer
  • Use hormone spiral within the last 5 years if they are under 60 years
  • Hysterectomy before cessation of menstrual periods if the women are below the age of 60

Sites / Locations

  • North Denmark Regional Hospital (Vendsyssel Hospital)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Symptomatic RCE

Healthy RCE

Symptomatic PL

Healthy PL

Arm Description

Bladder symptomatic group receiving red clover extract containing the two isoflavones formononetin and biochanin A. Isoflavone amount is 57.45 mg isoflavones daily (55.84 mg aglycones daily), in 70 ml red clover extract (35 ml twice daily, morning and evening with a meal)

Healthy group without bladder symptoms receiving red clover extract containing the two isoflavones formononetin and biochanin A. Isoflavone amount is 57.45 mg isoflavones daily (55.84 mg aglycones daily), in 70 ml red clover extract (35 ml twice daily, morning and evening with a meal)

Bladder symptomatic group receiving placebo

Healthy group without bladder symptoms receiving placebo

Outcomes

Primary Outcome Measures

Change from baseline microbiota composition in women suffering from UUI and OAB at three months follow-up
The microbiota composition is analyzed using sequencing of bacterial DNA. We are investigating the urinary, vaginal and gut microbiota. In women with urge urinary incontinence (UUI) and overactive bladder (OAB) receiving RCE (symptomatic RCE), a possible change in the urinary, vaginal and fecal microbiota composition from baseline to three month follow-up, compared to controls receiving placebo (symptomatic PL) are investigated. Symptomatic RCE from baseline to follow-up vs. Symptomatic PL from baseline to follow-up
Change in baseline microbiota composition at three months follow-up
The microbiota composition is analyzed using sequencing of bacterial DNA. Comparison of healthy women without bladder symptoms receiving RCE (healthy RCE) at baseline to three months follow-up compared to controls (healthy PL) from baseline to follow-up. Healthy RCE from baseline to follow-up vs. Healthy PL from baseline to follow-up
Difference in baseline microbiota composition between women with and without UUI and OAB
The microbiota composition is analyzed using sequencing of bacterial DNA. Is there a difference in the urinary, vaginal and gut microbiota in women with and without urge urinary incontinence (UUI) and overactive bladder (OAB) at baseline? Symptomatic PL baseline vs. Healthy PL baseline

Secondary Outcome Measures

Comparison of the urinary, vaginal, and fecal microbiota
The microbiota composition is analyzed using sequencing of bacterial DNA. This composition is evaluated using alpha-diversity (measured based on number of unique bacteria as well as Shannon diversity and phylogenic diversity) and beta-diversity, as indicated by unifrac distance and bray-Curtis dissimilarity. Comparison of the urinary, vaginal, and fecal microbiota composition at baseline. All the different compartments are measured using the same Units of Measure. Healthy PL baseline urinary vs. Healthy PL baseline vaginal vs. Healthy PL baseline gut
Change in overactive bladder symptoms from baseline in women suffering from UUI and OAB at three months follow-up
Overactive bladder symptoms are measured using the questionnaire International Consultation on Incontinence Questionnaire (ICIQ) Overactive Bladder (ICIQ-OAB). Comparison of symptom scores in women with UUI and OAB before and after treatment with RCE compared to placebo. Symptomatic RCE from baseline to follow-up vs. Symptomatic PL from baseline to follow-up
Change in urinary incontinence symptoms from baseline in women suffering from UUI and OAB at three months follow-up
Urinary incontinence symptoms are measured using the questionnaire International Consultation on Incontinence Questionnaire (ICIQ) Urinary Incontinence Short Form (ICIQ-UI-SF). Comparison of symptom scores in women with UUI and OAB before and after treatment with RCE compared to placebo. Symptomatic RCE from baseline to follow-up vs. Symptomatic PL from baseline to follow-up
Change in blood estrogen levels from baseline to three months follow-up
Blood estrogen levels are measured from serum blood samples. Blood samples are taken at baseline before RCE and PL intake and after three months treatment.
Change in blood isoflavone levels from baseline to three months follow-up
Blood isoflavone levels are measured in ng/mL from plasma blood samples. Blood samples are taken at baseline before RCE and PL intake and after three months treatment.
Change in blood equol levels from baseline to three months follow-up
Blood equol levels are measured in nmol/L from plasma blood samples. Blood samples are taken at baseline before RCE and PL intake and after three months treatment.
Change in gastrointestinal symptoms from baseline to three months follow-up
Gastrointestinal symptoms are measured using Rom IV criteria before and after RCE and PL intake.
Change in Irritable Bowel Syndrome Severity Score Scale from baseline to three months follow-up
Gastrointestinal symptoms are measured using the Irritable Bowel Syndrome Severity Score Scale before and after RCE and PL intake.
Change in Gastrointestinal Symptom Rating Scale from baseline to three months follow-up
Gastrointestinal symptoms are measured using the Gastrointestinal Symptom Rating Scale before and after RCE and PL intake.

Full Information

First Posted
August 3, 2021
Last Updated
April 25, 2023
Sponsor
Vendsyssel Hospital
Collaborators
University of Aarhus
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1. Study Identification

Unique Protocol Identification Number
NCT05013593
Brief Title
Red Clover Isoflavones in Postmenopausal Women With Urge Urinary Incontinence and Overactive Bladder
Official Title
The Effect of Red Clover Isoflavones on Urinary Microbiota Composition and Interaction With the Urothelium in Postmenopausal Women
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
July 15, 2019 (Actual)
Primary Completion Date
October 20, 2021 (Actual)
Study Completion Date
October 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vendsyssel Hospital
Collaborators
University of Aarhus

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to investigate the effect of red clover isoflavones in postmenopausal women with and without urge urinary incontinence and overactive bladder

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urge Incontinence, Overactive Bladder
Keywords
Microbiota, Microbiome

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Double-blinded, randomized, placebo-controlled three-month trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
108 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Symptomatic RCE
Arm Type
Experimental
Arm Description
Bladder symptomatic group receiving red clover extract containing the two isoflavones formononetin and biochanin A. Isoflavone amount is 57.45 mg isoflavones daily (55.84 mg aglycones daily), in 70 ml red clover extract (35 ml twice daily, morning and evening with a meal)
Arm Title
Healthy RCE
Arm Type
Experimental
Arm Description
Healthy group without bladder symptoms receiving red clover extract containing the two isoflavones formononetin and biochanin A. Isoflavone amount is 57.45 mg isoflavones daily (55.84 mg aglycones daily), in 70 ml red clover extract (35 ml twice daily, morning and evening with a meal)
Arm Title
Symptomatic PL
Arm Type
Placebo Comparator
Arm Description
Bladder symptomatic group receiving placebo
Arm Title
Healthy PL
Arm Type
Placebo Comparator
Arm Description
Healthy group without bladder symptoms receiving placebo
Intervention Type
Dietary Supplement
Intervention Name(s)
Red Clover Extract (RCE)
Intervention Description
Red clover extract containing isoflavones Formononetin and biochanin A together with a heterogenous culture of probiotic lactic acid bacteria, and a natural sugar free raspberry/orange flavor. Isoflavone amount is 57.45 mg isoflavones daily (55.84 mg aglycones daily), in 70 ml red clover extract (35 ml twice daily, morning and evening together with a meal)
Intervention Type
Other
Intervention Name(s)
Placebo (PL)
Intervention Description
Placebo containing water, brown coloring, and natural sugar free raspberry/orange flavor.
Primary Outcome Measure Information:
Title
Change from baseline microbiota composition in women suffering from UUI and OAB at three months follow-up
Description
The microbiota composition is analyzed using sequencing of bacterial DNA. We are investigating the urinary, vaginal and gut microbiota. In women with urge urinary incontinence (UUI) and overactive bladder (OAB) receiving RCE (symptomatic RCE), a possible change in the urinary, vaginal and fecal microbiota composition from baseline to three month follow-up, compared to controls receiving placebo (symptomatic PL) are investigated. Symptomatic RCE from baseline to follow-up vs. Symptomatic PL from baseline to follow-up
Time Frame
From baseline to three months follow-up
Title
Change in baseline microbiota composition at three months follow-up
Description
The microbiota composition is analyzed using sequencing of bacterial DNA. Comparison of healthy women without bladder symptoms receiving RCE (healthy RCE) at baseline to three months follow-up compared to controls (healthy PL) from baseline to follow-up. Healthy RCE from baseline to follow-up vs. Healthy PL from baseline to follow-up
Time Frame
From baseline to three months follow-up
Title
Difference in baseline microbiota composition between women with and without UUI and OAB
Description
The microbiota composition is analyzed using sequencing of bacterial DNA. Is there a difference in the urinary, vaginal and gut microbiota in women with and without urge urinary incontinence (UUI) and overactive bladder (OAB) at baseline? Symptomatic PL baseline vs. Healthy PL baseline
Time Frame
Baseline
Secondary Outcome Measure Information:
Title
Comparison of the urinary, vaginal, and fecal microbiota
Description
The microbiota composition is analyzed using sequencing of bacterial DNA. This composition is evaluated using alpha-diversity (measured based on number of unique bacteria as well as Shannon diversity and phylogenic diversity) and beta-diversity, as indicated by unifrac distance and bray-Curtis dissimilarity. Comparison of the urinary, vaginal, and fecal microbiota composition at baseline. All the different compartments are measured using the same Units of Measure. Healthy PL baseline urinary vs. Healthy PL baseline vaginal vs. Healthy PL baseline gut
Time Frame
Baseline
Title
Change in overactive bladder symptoms from baseline in women suffering from UUI and OAB at three months follow-up
Description
Overactive bladder symptoms are measured using the questionnaire International Consultation on Incontinence Questionnaire (ICIQ) Overactive Bladder (ICIQ-OAB). Comparison of symptom scores in women with UUI and OAB before and after treatment with RCE compared to placebo. Symptomatic RCE from baseline to follow-up vs. Symptomatic PL from baseline to follow-up
Time Frame
From baseline to three months follow-up
Title
Change in urinary incontinence symptoms from baseline in women suffering from UUI and OAB at three months follow-up
Description
Urinary incontinence symptoms are measured using the questionnaire International Consultation on Incontinence Questionnaire (ICIQ) Urinary Incontinence Short Form (ICIQ-UI-SF). Comparison of symptom scores in women with UUI and OAB before and after treatment with RCE compared to placebo. Symptomatic RCE from baseline to follow-up vs. Symptomatic PL from baseline to follow-up
Time Frame
From baseline to three months follow-up
Title
Change in blood estrogen levels from baseline to three months follow-up
Description
Blood estrogen levels are measured from serum blood samples. Blood samples are taken at baseline before RCE and PL intake and after three months treatment.
Time Frame
From baseline to three months follow-up
Title
Change in blood isoflavone levels from baseline to three months follow-up
Description
Blood isoflavone levels are measured in ng/mL from plasma blood samples. Blood samples are taken at baseline before RCE and PL intake and after three months treatment.
Time Frame
From baseline to three months follow-up
Title
Change in blood equol levels from baseline to three months follow-up
Description
Blood equol levels are measured in nmol/L from plasma blood samples. Blood samples are taken at baseline before RCE and PL intake and after three months treatment.
Time Frame
From baseline to three months follow-up
Title
Change in gastrointestinal symptoms from baseline to three months follow-up
Description
Gastrointestinal symptoms are measured using Rom IV criteria before and after RCE and PL intake.
Time Frame
From baseline to three months follow-up
Title
Change in Irritable Bowel Syndrome Severity Score Scale from baseline to three months follow-up
Description
Gastrointestinal symptoms are measured using the Irritable Bowel Syndrome Severity Score Scale before and after RCE and PL intake.
Time Frame
From baseline to three months follow-up
Title
Change in Gastrointestinal Symptom Rating Scale from baseline to three months follow-up
Description
Gastrointestinal symptoms are measured using the Gastrointestinal Symptom Rating Scale before and after RCE and PL intake.
Time Frame
From baseline to three months follow-up

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Postmenopausal (more than 5 years since last menstruation) Read and understand Danish Exclusion Criteria: Participants receive treatment with estrogen both oral, transdermal, and topical within three months prior to inclusion in the study Participants take estrogen-like compounds (isoflavones) three months prior to inclusion in the study Participants take prebiotic and/or probiotic supplements within three months prior to study inclusion Receive antibiotics (any) within three months prior to inclusion in the study Recurrent urinary tract infections (defined as ≥ 2 infections in the last six months or ≥ 3 infections during the last year) Acute urinary tract infection defined as positive urine culture and symptoms of acute cystitis Previous or current diseases of the digestive and/or urinary systems evaluated by PI (including, but not limited to inflammatory bowel disease (IBD) and cancer) Current or prior suffering from breast, ovary, and/or endometrial cancer Use hormone spiral within the last 5 years if they are under 60 years Hysterectomy before cessation of menstrual periods if the women are below the age of 60
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Annemarie B Villadsen
Organizational Affiliation
Vendsyssel Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
North Denmark Regional Hospital (Vendsyssel Hospital)
City
Hjørring
ZIP/Postal Code
9800
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual deidentified participant data will be shared upon article publication. Microbiome data (DNA sequences) will be uploaded to the Sequence Read Archive (SRA) at the National Center for Biotechnology Information (NCBI).
IPD Sharing Time Frame
Data will become available upon article publication at NCBI.
IPD Sharing Access Criteria
All will have access to the microbiome data

Learn more about this trial

Red Clover Isoflavones in Postmenopausal Women With Urge Urinary Incontinence and Overactive Bladder

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