Trial Outcomes & Findings for Investigation of the Effect of the Female Urinary Microbiome on Incontinence (NCT NCT02835846)

Last Updated: 2021-09-23

Results Overview

The relative abundance of Lactobacillus to total microbes per sample was measured before and after treatment. The within-participant change in relative abundance of Lactobacillus was calculated subtracting pre-treatment from post-treatment.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

35 participants

Primary outcome timeframe

0, 12 weeks

Results posted on

2021-09-23

Participant Flow

Participant milestones

Participant milestones
Measure	Estrogen Arm The intervention for this study is an estrogen cream (i.e., Premarin Cream®). Women in this study will receive this estrogen cream and apply it to their vagina twice weekly for 12 weeks Estrogen Cream: Participants are provided a vaginal estrogen cream (i.e., Premarin Cream® 0.625 mg conjugated estrogen/gram) and instructed to use 0.5 grams with an applicator twice weekly for 12 weeks.
Overall Study STARTED	35
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Investigation of the Effect of the Female Urinary Microbiome on Incontinence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Estrogen Arm n=35 Participants The intervention for this study is an estrogen cream (i.e., Premarin Cream®). Women in this study will receive this estrogen cream and apply it to their vagina twice weekly for 12 weeks Estrogen Cream: Participants are provided a vaginal estrogen cream (i.e., Premarin Cream® 0.625 mg conjugated estrogen/gram) and instructed to use 0.5 grams with an applicator twice weekly for 12 weeks.
Age, Continuous	69 years n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized White	23 Participants n=5 Participants
Race/Ethnicity, Customized African American	8 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants
Body mass index	28.5 kg/m^2 n=5 Participants
Number of vaginal deliveries	3 deliveries n=5 Participants
Prior hysterectomy Prior hysterectomy	16 Participants n=5 Participants
Prior hysterectomy No prior hysterectomy	19 Participants n=5 Participants
Stage of prolapse 0	9 Participants n=5 Participants
Stage of prolapse 1	11 Participants n=5 Participants
Stage of prolapse 2	15 Participants n=5 Participants
Ovaries removed Ovaries removed	7 Participants n=5 Participants
Ovaries removed Ovaries not removed	26 Participants n=5 Participants
Ovaries removed Unknown	2 Participants n=5 Participants
Previous incontinence surgery Previous incontinence surgery	2 Participants n=5 Participants
Previous incontinence surgery No previous incontinence surgery	33 Participants n=5 Participants
Postvoid residual	40 mL n=5 Participants

PRIMARY outcome

Timeframe: 0, 12 weeks

Population: Participants with catheterized urine samples taken pre-treatment and post-treatment

Outcome measures

Outcome measures
Measure	Estrogen Arm n=18 Participants The intervention for this study is an estrogen cream (i.e., Premarin Cream®). Women in this study will receive this estrogen cream and apply it to their vagina twice weekly for 12 weeks Estrogen Cream: Participants are provided a vaginal estrogen cream (i.e., Premarin Cream® 0.625 mg conjugated estrogen/gram) and instructed to use 0.5 grams with an applicator twice weekly for 12 weeks.
Change in the Relative Abundance of Lactobacillus	0.275 proportion of total microbes Standard Deviation 0.345

SECONDARY outcome

Timeframe: 0, 12 weeks

Population: All participants who completed the OAB symptoms questionnaire at baseline and after treatment

OAB symptoms are measured using the Overactive Bladder Questionnaire (OAB-q). The OAB-q symptom score ranges from 0-100 with higher scores indicating greater symptom severity. A change score is calculated as the post-treatment score minus the pre-treatment score.

Outcome measures

Outcome measures
Measure	Estrogen Arm n=24 Participants The intervention for this study is an estrogen cream (i.e., Premarin Cream®). Women in this study will receive this estrogen cream and apply it to their vagina twice weekly for 12 weeks Estrogen Cream: Participants are provided a vaginal estrogen cream (i.e., Premarin Cream® 0.625 mg conjugated estrogen/gram) and instructed to use 0.5 grams with an applicator twice weekly for 12 weeks.
Change in OAB Symptoms	-21 units on a scale Interval -39.0 to -8.0

SECONDARY outcome

Timeframe: 0, 12 weeks

Population: All participants who completed the OAB symptoms questionnaire and have catheterized urine samples at baseline and after treatment

The investigators will determine whether change in OAB symptoms using the OAB-q before and after treatment is associated with the change in participants' relative abundance of Lactobacillus before and after treatment. The OAB-q symptom score ranges from 0-100 with higher scores indicating greater symptom severity.

Outcome measures

Outcome measures
Measure	Estrogen Arm n=18 Participants The intervention for this study is an estrogen cream (i.e., Premarin Cream®). Women in this study will receive this estrogen cream and apply it to their vagina twice weekly for 12 weeks Estrogen Cream: Participants are provided a vaginal estrogen cream (i.e., Premarin Cream® 0.625 mg conjugated estrogen/gram) and instructed to use 0.5 grams with an applicator twice weekly for 12 weeks.
OAB Symptoms Associated With Relative Abundance of Lactobacillus	-0.32 Spearman's rho

SECONDARY outcome

Timeframe: 0, 12 weeks

Population: Assays were performed on a subset of participants due to resource constraints.

The investigators will compare participants' AMP activity levels before and after treatment. AMP activity level is measured as the diffusion of AMPs in bacterial agar from the center of the well to which the patient's purified biological sample is applied. The diffusion of AMPs in the agar results in the killing of bacteria and a clearing around the well. This clearing of bacterial growth is measured in square millimeters and then normalized to the total peptide concentration. Change is calculated as the post-treatment AMP activity level minus the pre-treatment AMP activity level.

Outcome measures

Outcome measures
Measure	Estrogen Arm n=2 Participants The intervention for this study is an estrogen cream (i.e., Premarin Cream®). Women in this study will receive this estrogen cream and apply it to their vagina twice weekly for 12 weeks Estrogen Cream: Participants are provided a vaginal estrogen cream (i.e., Premarin Cream® 0.625 mg conjugated estrogen/gram) and instructed to use 0.5 grams with an applicator twice weekly for 12 weeks.
Change in Urothelial Antimicrobial Peptide (AMP) Levels	0.14 normalized bacterial growth inhibition Interval 0.07 to 0.22

SECONDARY outcome

Timeframe: 0, 12 weeks

Population: Assays were performed on a subset of participants due to resource constraints.

The investigators will determine whether any change in OAB symptoms using the OAB-q before and after treatment is associated with the change in participants' AMP levels before and after treatment.

Outcome measures

Outcome measures
Measure	Estrogen Arm n=2 Participants The intervention for this study is an estrogen cream (i.e., Premarin Cream®). Women in this study will receive this estrogen cream and apply it to their vagina twice weekly for 12 weeks Estrogen Cream: Participants are provided a vaginal estrogen cream (i.e., Premarin Cream® 0.625 mg conjugated estrogen/gram) and instructed to use 0.5 grams with an applicator twice weekly for 12 weeks.
Change in OAB Symptoms Associated With Change in AMP Levels	-1 Spearman's rho

Adverse Events

Estrogen Arm

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Alan J Wolfe

Loyola University Chicago

Phone: 7082165814

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place