Alterations in the Vaginal Microenvironment Using a Non-pharmacological Intervention

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03739983
• Collaborator: American Cancer Society, Inc. (Other)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 3.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Breast cancer patients commonly take medications to reduce the risk of recurrence, including aromatase inhibitors (AIs). AIs can cause significant side effects that reduce patient adherence. Early discontinuation of AI therapy results in an increased risk of cancer recurrence and increased risk of breast cancer-related death. Common side effects include vaginal dryness and vulvovaginal atrophy leading to worsening sexual function. To increase AI adherence, the investigators will study a non-pharmaceutical Vaginal Renewal Program (VRP) aimed at stimulating nitric oxide production to consequently increase vaginal lubrication, and improve the symptoms of vulvovaginal atrophy.

Condition or Disease	Intervention/Treatment	Phase
Adherence, Medication	Device: Vaginal Renewal Program	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Prospective Simon two-stage study designProspective Simon two-stage study design
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Alterations in the Vaginal Microenvironment Using a Non-pharmacological Intervention for Breast Cancer Patients Treated With Aromatase Inhibitors
• Actual Study Start Date: Nov 19, 2019
• Actual Primary Completion Date: Mar 10, 2020
• Actual Study Completion Date: Mar 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VRP Therapy All subjects on this study will receive the Vaginal Renewal Program intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time.	Device: Vaginal Renewal Program; Therapeutic vibrating wand.; Other Names: FeMani Vibrating Massage Wand

Outcome Measures

Primary Outcome Measures

1. Percentage of Superficial Vaginal Cells [up to 12 weeks]

   The investigators expect the percentage of superficial vaginal cells to be greater at the post-intervention time point when compared to the pre-intervention time point. If the percentage of superficial vaginal cells is ≥ 4% following the intervention, then the response will be considered positive.

Secondary Outcome Measures

1. Change in Vaginal pH [up to 12 weeks]

   Changes in the vaginal pH will be analyzed to determine the extent to which the changes correlate with changes in the primary outcome and with patient reported outcomes. Given the longitudinal nature of the study, linear and generalized linear mixed effects models will be fit to the data gathered. The restricted maximum likelihood (REML) criterion will be used and 95% semi-parametrically bootstrapped confidence intervals will be obtained for all parameters. All statistical analyses will be conducted using R (R Core Team 2014).

2. Patient Reported Outcomes: Number of Subjects With Improved Anxiety [up to 12 weeks]

   Number of subjects with improved anxiety outcomes per over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Emotional Distress - Anxiety scale measures patient perceived changes in anxiety and includes 8 questions that they answer about their emotional state in the past 7 days. Descriptive answers are scored from 1 (never) to 5 (always). The total possible range of scores is from 8-40, with higher scores indicating a worse outcome.

3. Patient Reported Outcomes: Number of Subjects With Improved Depression [up to 12 weeks]

   Number of subjects with improved depression outcomes over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Emotional Distress - Depression scale measures patient perceived changes in depression and includes 8 questions that they answer about their emotional state in the past 7 days. Descriptive answers are scored from 1 (never) to 5 (always). The total possible range of scores is from 8-40, with higher scores indicating a worse outcome.

4. Patient Reported Outcomes: Number of Subjects With Improved Sexual Function Outcomes [up to 12 weeks]

   Number of subjects with improved sexual function outcomes over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Sexual Function Profile scale measures patient perceived changes in sexual function and includes 10 questions that they answer about their functional state. Descriptive answers include 'Not at all', 'A little bit', 'Somewhat', 'Quite a bit', or 'Very', and will be summarized with descriptive statistics.

5. Patient Reported Outcomes: Number of Subjects With Improved Global Health [up to 12 weeks]

   Number of subjects with improved global health over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Global Health scale measures patient perceived changes in health and includes 10 questions that they answer about their perceived health in the past 7 days. Higher scores indicate a higher perceived level of overall health.

6. Patient Reported Outcomes: Number of Subjects With Improved Sex Life [up to 12 weeks]

   Number of subjects with improved sex life over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Global Satisfaction with Sex Life scale measures patient perceived changes in the satisfaction of their sex life and includes 7 questions that they answer about their perceived state. Descriptive answers include 'Not at all', 'A little bit', 'Somewhat', 'Quite a bit', or 'Very', and will be summarized with descriptive statistics.

Other Outcome Measures

1. Adherence to AI Therapy [up to 12 weeks]

   Adherence to AI therapy will be determined using patient-reported logs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have completed active primary treatment

• defined as surgery chemotherapy and/or radiation for the treatment of breast cancer

• Does not include immunotherapy or other targeted therapies such as trastuzumab, CDK 4/6 or mTOR inhibitors

• Have been receiving AIs for at least 6 months prior to enrollment

• Plan to continue AIs for an additional 3 months

• Amenorrhea for at least 12 months at enrollment

• Participants must be able to read and write in English

• Participants must have < 2% superficial vaginal cells on cytologic evaluation

Exclusion Criteria:

• Pre-existing hypertonic pelvic floor dysfunction identified in the medical record

• Unresolved or recurrent vaginismus identified in the medical record

• Aversion to touching one's own body, including genitals, or using vibration therapy on the genitals

• Currently receiving estrogen therapy, including topical and/or systemic estrogens

• Have received estrogen therapy within 6 months of study enrollment, including topical and/or systemic estrogens

• Any surgical procedure to the vagina or vulva, excluding office biopsies, within the previous 12 months

• Receipt of pelvic or vaginal or vulvar radiation therapy within the 12 months prior to enrollment or if the subject is anticipated to receive radiation targeted to any of these 3 locations within 6 months following enrollment

• Any use of the VRP off study within the last 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• American Cancer Society, Inc.

Investigators

• Principal Investigator: Ryan Spencer, University of Wisconsin, Madison

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 3, 2019

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT03739983
• Other Study ID Numbers: UW17032; 2018-0633; A532820; SMPH/OBSTET & GYNEC/GYNEC ONC; NCI-2018-02729; Protocol Version 10/3/2019
• First Posted: Nov 14, 2018
• Last Update Posted: Oct 20, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Study Results

Participant Flow

Recruitment Details	Participants were recruited with the help of the University of Wisconsin Carbone Cancer Center in November and December 2019. Recruitment was suspended in March 2020 due to the COVID-19 pandemic.

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time. Vaginal Renewal Program: Therapeutic vibrating wand.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time. Vaginal Renewal Program: Therapeutic vibrating wand.
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	2 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Superficial Vaginal Cells
Description	The investigators expect the percentage of superficial vaginal cells to be greater at the post-intervention time point when compared to the pre-intervention time point. If the percentage of superficial vaginal cells is ≥ 4% following the intervention, then the response will be considered positive.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

End of study samples unavailable, decision was made not to analyze primary outcome as it was not powered to produce meaningful results.

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program (VRP) intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time.
Measure Participants	0

2. Secondary Outcome

Title	Change in Vaginal pH
Description	Changes in the vaginal pH will be analyzed to determine the extent to which the changes correlate with changes in the primary outcome and with patient reported outcomes. Given the longitudinal nature of the study, linear and generalized linear mixed effects models will be fit to the data gathered. The restricted maximum likelihood (REML) criterion will be used and 95% semi-parametrically bootstrapped confidence intervals will be obtained for all parameters. All statistical analyses will be conducted using R (R Core Team 2014).
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

No data to analyze.

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program (VRP) intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time.
Measure Participants	0

3. Secondary Outcome

Title	Patient Reported Outcomes: Number of Subjects With Improved Anxiety
Description	Number of subjects with improved anxiety outcomes per over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Emotional Distress - Anxiety scale measures patient perceived changes in anxiety and includes 8 questions that they answer about their emotional state in the past 7 days. Descriptive answers are scored from 1 (never) to 5 (always). The total possible range of scores is from 8-40, with higher scores indicating a worse outcome.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program (VRP) intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time.
Measure Participants	2
Count of Participants [Participants]	1 50%

4. Secondary Outcome

Title	Patient Reported Outcomes: Number of Subjects With Improved Depression
Description	Number of subjects with improved depression outcomes over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Emotional Distress - Depression scale measures patient perceived changes in depression and includes 8 questions that they answer about their emotional state in the past 7 days. Descriptive answers are scored from 1 (never) to 5 (always). The total possible range of scores is from 8-40, with higher scores indicating a worse outcome.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

only 1 participant completed this survey

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program (VRP) intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time.
Measure Participants	1
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Patient Reported Outcomes: Number of Subjects With Improved Sexual Function Outcomes
Description	Number of subjects with improved sexual function outcomes over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Sexual Function Profile scale measures patient perceived changes in sexual function and includes 10 questions that they answer about their functional state. Descriptive answers include 'Not at all', 'A little bit', 'Somewhat', 'Quite a bit', or 'Very', and will be summarized with descriptive statistics.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

Incomplete data, unable to evaluate.

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program (VRP) intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time.
Measure Participants	0

6. Secondary Outcome

Title	Patient Reported Outcomes: Number of Subjects With Improved Global Health
Description	Number of subjects with improved global health over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Global Health scale measures patient perceived changes in health and includes 10 questions that they answer about their perceived health in the past 7 days. Higher scores indicate a higher perceived level of overall health.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program (VRP) intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time.
Measure Participants	2
Count of Participants [Participants]	0 0%

7. Secondary Outcome

Title	Patient Reported Outcomes: Number of Subjects With Improved Sex Life
Description	Number of subjects with improved sex life over baseline. The PROMIS (Patient Reported Outcomes Measurement Information System) Global Satisfaction with Sex Life scale measures patient perceived changes in the satisfaction of their sex life and includes 7 questions that they answer about their perceived state. Descriptive answers include 'Not at all', 'A little bit', 'Somewhat', 'Quite a bit', or 'Very', and will be summarized with descriptive statistics.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

Incomplete data, unable to evaluate.

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program (VRP) intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time.
Measure Participants	0

8. Other Pre-specified Outcome

Title	Adherence to AI Therapy
Description	Adherence to AI therapy will be determined using patient-reported logs.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

No data to analyze

Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program (VRP) intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time.
Measure Participants	0

Adverse Events

Time Frame	up to 3 months
Arm/Group Title	VRP Therapy
Arm/Group Description	All subjects on this study will receive the Vaginal Renewal Program intervention. Enrolled subjects will receive inperson instruction on how to perform the VRP. Subjects will be encouraged to use the device for 3-4 days per week for 5 minutes at a time. Vaginal Renewal Program: Therapeutic vibrating wand.
All Cause Mortality
	VRP Therapy
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	VRP Therapy
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	VRP Therapy
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Reproductive system and breast disorders
Irritation	1/2 (50%)	1
Vulvar Stinging	1/2 (50%)	1
Perineal Chaffing	1/2 (50%)	1

Limitations/Caveats

This study was terminated early with 2 participants due to the COVID-19 pandemic. It is not powered for meaningful results.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.