Trial Outcomes & Findings for Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy (NCT NCT03996603)

NCT ID: NCT03996603

Last Updated: 2024-05-07

Results Overview

The relative abundance of the Lactobacillus genus, as measured by 16S ribosomal RNA (rRNA) gene sequencing, is the proportion of Lactobacillus genus among the total vaginal microbiome. After analysis of the gene sequencing, the total yield of bacteria at the genus level equals 1. The quantitative change in relative abundance of Lactobacillus among the community composition of bacteria in the vagina will be assessed from baseline to 8 weeks. The investigators hypothesize that a pre-specified statistically significant quantitative increase in the relative abundance of Lactobacillus will be seen among the participants that receive treatment.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

25 participants

Primary outcome timeframe

Baseline, 8 weeks

Results posted on

2024-05-07

Participant Flow

Participant milestones

Participant milestones
Measure
Conjugated Estrogens Cream
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
Control Cohort
No intervention will be given.
Overall Study
STARTED
20
5
Overall Study
COMPLETED
16
5
Overall Study
NOT COMPLETED
4
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Conjugated Estrogens Cream
n=20 Participants
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
Control Cohort
n=5 Participants
No intervention will be given.
Total
n=25 Participants
Total of all reporting groups
Age, Continuous
65.5 years
n=5 Participants
71 years
n=7 Participants
66 years
n=5 Participants
Sex: Female, Male
Female
20 Participants
n=5 Participants
5 Participants
n=7 Participants
25 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
5 Participants
n=5 Participants
2 Participants
n=7 Participants
7 Participants
n=5 Participants
Race (NIH/OMB)
White
14 Participants
n=5 Participants
3 Participants
n=7 Participants
17 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
20 Participants
n=5 Participants
5 Participants
n=7 Participants
25 Participants
n=5 Participants
Body Mass Index
27.3 kg/m^2
n=5 Participants
30.9 kg/m^2
n=7 Participants
27.3 kg/m^2
n=5 Participants
Parity
2 births
n=5 Participants
2 births
n=7 Participants
2 births
n=5 Participants
Spontaneous Vaginal Delivery
2 deliveries
n=5 Participants
1 deliveries
n=7 Participants
2 deliveries
n=5 Participants
Hysterectomy
10 Participants
n=5 Participants
2 Participants
n=7 Participants
12 Participants
n=5 Participants
Prior Prolapse Surgery
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Prior SUI Surgery
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Recurrent UTIs
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Diabetes Mellitus
4 Participants
n=5 Participants
0 Participants
n=7 Participants
4 Participants
n=5 Participants
Currently on OAB/UUI Medication(s)
3 Participants
n=5 Participants
2 Participants
n=7 Participants
5 Participants
n=5 Participants
Currently Sexually Active
12 Participants
n=5 Participants
2 Participants
n=7 Participants
14 Participants
n=5 Participants
Vaginal pH
6.8 pH
n=5 Participants
7 pH
n=7 Participants
7 pH
n=5 Participants
Vaginal Maturation Index
37.5 units on a scale
n=5 Participants
40 units on a scale
n=7 Participants
40 units on a scale
n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 8 weeks

The relative abundance of the Lactobacillus genus, as measured by 16S ribosomal RNA (rRNA) gene sequencing, is the proportion of Lactobacillus genus among the total vaginal microbiome. After analysis of the gene sequencing, the total yield of bacteria at the genus level equals 1. The quantitative change in relative abundance of Lactobacillus among the community composition of bacteria in the vagina will be assessed from baseline to 8 weeks. The investigators hypothesize that a pre-specified statistically significant quantitative increase in the relative abundance of Lactobacillus will be seen among the participants that receive treatment.

Outcome measures

Outcome measures
Measure
Conjugated Estrogens Cream
n=20 Participants
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
Control Cohort
n=5 Participants
No intervention will be given.
Quantitative Change in Relative Abundance of Lactobacillus Among the Community Composition of Bacteria in the Vagina
Baseline
0.07 Relative abundance
Interval 0.02 to 0.14
0.09 Relative abundance
Interval 0.03 to 0.45
Quantitative Change in Relative Abundance of Lactobacillus Among the Community Composition of Bacteria in the Vagina
8 weeks
0.12 Relative abundance
Interval 0.06 to 0.96
0.04 Relative abundance
Interval 0.04 to 0.2

SECONDARY outcome

Timeframe: Baseline, 8 weeks

The maturation value (MV) is calculated with the following formula: MV = % surface cells + (0.5 × % intermediate cells). The outcome data is reported as the delta change from baseline to 8 weeks. The data for the primary outcome has been entered using the "measure type - NUMBER" because the outcome is a delta or change in the vaginal maturation index.

Outcome measures

Outcome measures
Measure
Conjugated Estrogens Cream
n=20 Participants
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
Control Cohort
n=5 Participants
No intervention will be given.
Change in Vaginal Maturation Index (VMI)
Baseline
35 Change in vaginal maturation index value
Interval 10.0 to 47.5
42.5 Change in vaginal maturation index value
Interval 17.5 to 50.0
Change in Vaginal Maturation Index (VMI)
8 weeks
60 Change in vaginal maturation index value
Interval 50.0 to 65.0
47.5 Change in vaginal maturation index value
Interval 45.0 to 52.5

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Change in the vaginal pH from baseline to 8 weeks

Outcome measures

Outcome measures
Measure
Conjugated Estrogens Cream
n=20 Participants
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
Control Cohort
n=5 Participants
No intervention will be given.
Change in Vaginal pH
Baseline
7.25 Vaginal pH
Interval 6.5 to 7.5
7 Vaginal pH
Interval 5.5 to 8.0
Change in Vaginal pH
8 weeks
5 Vaginal pH
Interval 4.5 to 5.5
7 Vaginal pH
Interval 5.5 to 7.5

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Only one specimen resulted in a value for IL-10 post-treatment.

Change in the vaginal inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF from baseline to 8 weeks

Outcome measures

Outcome measures
Measure
Conjugated Estrogens Cream
n=20 Participants
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
Control Cohort
n=5 Participants
No intervention will be given.
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
IL-1b BASELINE
44.4 pg/mg
Interval 5.9 to 84.9
132.9 pg/mg
Interval 28.8 to 236.9
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
IL-1b 8 WEEKS
10.8 pg/mg
Interval 4.0 to 26.0
373.6 pg/mg
Interval 10.2 to 737.1
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
IL-4 BASELINE
10.0 pg/mg
Interval 5.3 to 23.1
18.1 pg/mg
Interval 2.3 to 33.8
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
IL-4 8 WEEKS
2.1 pg/mg
Interval 1.3 to 4.2
11.1 pg/mg
Interval 5.0 to 17.2
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
IL-8 BASELINE
3158.2 pg/mg
Interval 1956.2 to 8087.5
3724.3 pg/mg
Interval 2254.4 to 5194.2
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
IL-8 8 WEEKS
757.5 pg/mg
Interval 260.0 to 1980.3
7941.0 pg/mg
Interval 2247.8 to 13643.2
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
IL-10 BASELINE
22.5 pg/mg
Interval 14.9 to 38.2
12.7 pg/mg
Interval 1.7 to 22.1
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
IL-10 8 WEEKS
640.7 pg/mg
Only one specimen resulted a value for IL-10 post treatment.
7.0 pg/mg
Interval 5.1 to 14.3
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
TNF-a BASELINE
9.3 pg/mg
Interval 8.9 to 56.9
11.6 pg/mg
Interval 6.1 to 39.7
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
TNF-a 8 WEEKS
7.1 pg/mg
Interval 6.5 to 10.1
12.0 pg/mg
Interval 7.2 to 30.5
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
MCP-1 BASELINE
102.5 pg/mg
Interval 22.1 to 232.1
29.1 pg/mg
Interval 24.4 to 186.7
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
MCP-1 8 WEEKS
6.7 pg/mg
Interval 3.3 to 31.3
59.0 pg/mg
Interval 19.8 to 79.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 8 weeks

Population: There was only one participant and there was no range.

Quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) from baseline to 8 weeks.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 8 weeks

Population: This data was never collected.

Quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) from baseline to 8 weeks.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 8 weeks

Population: This data was never collected.

Change in the concentration of bladder inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF from baseline to 8 weeks

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 8 weeks

Population: This data was never collected.

Change in the concentration of rectal inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF from baseline to 8 weeks

Outcome measures

Outcome data not reported

Adverse Events

Conjugated Estrogens Cream

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Control Cohort

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

Kyle Norris, MD Principal Investigator

University of Alabama at Birmingham

Phone: (205) 934-1704

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place