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Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor (PET)

Primary Purpose

Pelvic Organ Prolapse, Menopause

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Premarin
Placebo
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Pelvic Organ Prolapse focused on measuring Pelvic organ prolapse, Menopause, Estrogen, Premarin

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Women, still with uterus, planning total hysterectomy as part of surgical repair for pelvic organ prolapse
  • Symptomatic anterior and/or apical vaginal prolapse greater than or equal to Stage 2 (i.e., bulge extends to at least 1 cm of the hymen or beyond)
  • Women between 1 and 10 years after menopause. Menopause is defined as one year of amenorrhea or surgical ovariectomy.
  • Age 40-70 years old
  • No estrogen replacement therapy in the last 1 month
  • Physically capable of daily application of vaginal cream

Exclusion Criteria:

  • BMI >35
  • Prior surgical repair of prolapse involving the vaginal cuff.
  • Prior total hysterectomy
  • Premenopausal or postmenopausal >10 years
  • Prior steroid hormone replacement therapy of duration >1 month (oral or vaginal estrogen, testosterone or corticosteroids)
  • History of connective tissue disease (Ehlers-Danlos, Marfan, etc)
  • History of vaginal radiation
  • Contraindications for estrogen replacement therapy (current, or history of, spontaneous deep vein thrombosis, stroke, coronary artery disease, breast or endometrial cancer)
  • Concurrent use of steroid cream for treatment of Lichen sclerosis
  • Recent history (within last month) of vaginal infection or vaginitis
  • Current tobacco use

Sites / Locations

  • University of Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Premarin

Placebo

Arm Description

Premarin cream 0.625mg/1gm. Applied to vagina by applicator as 1gm nightly for 2 weeks then 1gm 2 nights per week for 4-6 weeks or until day of surgery.

Placebo cream, applied to vagina by applicator as 1gm nightly for 2 weeks then 1gm 2 nights per week for 4-6 weeks or until day of surgery.

Outcomes

Primary Outcome Measures

Vaginal Wall Composition: Epithelium (Intention to Treat)
Will assess vaginal wall histology - thicknesses of epithelium
Vaginal Wall Composition: Epithelium (Per-Protocol)
Will assess vaginal wall histology - thicknesses of epithelium
Vaginal Wall Composition: Muscularis (Intention to Treat)
Will assess vaginal wall histology - thicknesses of muscularis
Vaginal Wall Composition: Muscularis (Per-Protocol)
Will assess vaginal wall histology - thicknesses of muscularis
hCOL1A1, Per-Protocol
Data represent ratio of total mRNA relative to postmenopausal external control.
Total Collagen Content in Vaginal Muscularis, (Per-Protocol)
Will assess hydroxy-proline assays as index of amount of collagen
Vaginal Wall Degradative Activity, Muscularis, MMP-9
Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
Vaginal Wall Composition: Lamina Propria (Intention to Treat)
Will assess vaginal wall histology - thickness of lamina propria.
Vaginal Wall Composition: Lamina Propria (Per-Protocol)
Will assess vaginal wall histology - thickness of lamina propria
hCOL3, (Per-Protocol)
Data represent ratio of total mRNA relative to postmenopausal external control.
Lysyl Oxidase (LOX) (Per-Protocol)
Data represent ratio of total mRNA relative to postmenopausal external control.
LOXL1 (Per-Protocol)
Data represent ratio of total mRNA relative to postmenopausal external control.
Tropoelastin (Per-Protocol)
Data represent ratio of total mRNA relative to postmenopausal external control.
TGFB1 (Per-Protocol)
Data represent ratio of total mRNA relative to postmenopausal external control.
Vaginal Wall Degradative Activity, Mucosa, MMP-9
Will assess zymograms for total matrix metalloprotease (MMP) 9 activity

Secondary Outcome Measures

Serum Estrone Levels, Baseline
Serum Estrone Levels, Surgery
Serum Estradiol Levels, Baseline
Serum Estradiol Levels, Surgery
Estimated Blood Loss
Intraoperative estimated blood loss

Full Information

First Posted
January 23, 2013
Last Updated
September 18, 2014
Sponsor
University of Texas Southwestern Medical Center
Collaborators
American Urogynecologic Society Foundation Astellas Research Award
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1. Study Identification

Unique Protocol Identification Number
NCT01778985
Brief Title
Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
Acronym
PET
Official Title
Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
American Urogynecologic Society Foundation Astellas Research Award

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a study to determine how vaginal estrogen cream given for several weeks before pelvic reconstructive therapy will effect elastic fiber assembly in the muscularis layer of the vaginal wall. Postmenopausal women with at least Stage 2 pelvic organ prolapse will receive either estrogen vaginal cream or placebo cream 6-8 weeks prior to reconstructive surgery. At time of surgery, full thickness biopsies will be obtained from a standardized location at the top of vagina. The investigators will measure the thickness of the vaginal muscularis, elastic fiber number and morphology, and analyze if elastic fiber synthesis or degradation is affected by estrogen therapy. The results will provide important data to support a larger clinical trial to determine if preoperative and maintenance estrogen therapy alter long-term success rates of pelvic reconstructive surgery for pelvic organ prolapse.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pelvic Organ Prolapse, Menopause
Keywords
Pelvic organ prolapse, Menopause, Estrogen, Premarin

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Premarin
Arm Type
Experimental
Arm Description
Premarin cream 0.625mg/1gm. Applied to vagina by applicator as 1gm nightly for 2 weeks then 1gm 2 nights per week for 4-6 weeks or until day of surgery.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo cream, applied to vagina by applicator as 1gm nightly for 2 weeks then 1gm 2 nights per week for 4-6 weeks or until day of surgery.
Intervention Type
Drug
Intervention Name(s)
Premarin
Other Intervention Name(s)
Conjugated equine estrogen
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo cream
Primary Outcome Measure Information:
Title
Vaginal Wall Composition: Epithelium (Intention to Treat)
Description
Will assess vaginal wall histology - thicknesses of epithelium
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Vaginal Wall Composition: Epithelium (Per-Protocol)
Description
Will assess vaginal wall histology - thicknesses of epithelium
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Vaginal Wall Composition: Muscularis (Intention to Treat)
Description
Will assess vaginal wall histology - thicknesses of muscularis
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Vaginal Wall Composition: Muscularis (Per-Protocol)
Description
Will assess vaginal wall histology - thicknesses of muscularis
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
hCOL1A1, Per-Protocol
Description
Data represent ratio of total mRNA relative to postmenopausal external control.
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Total Collagen Content in Vaginal Muscularis, (Per-Protocol)
Description
Will assess hydroxy-proline assays as index of amount of collagen
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Vaginal Wall Degradative Activity, Muscularis, MMP-9
Description
Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Vaginal Wall Composition: Lamina Propria (Intention to Treat)
Description
Will assess vaginal wall histology - thickness of lamina propria.
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Vaginal Wall Composition: Lamina Propria (Per-Protocol)
Description
Will assess vaginal wall histology - thickness of lamina propria
Time Frame
Time of surgery, i.e. 6-8 weeks of intervention
Title
hCOL3, (Per-Protocol)
Description
Data represent ratio of total mRNA relative to postmenopausal external control.
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Lysyl Oxidase (LOX) (Per-Protocol)
Description
Data represent ratio of total mRNA relative to postmenopausal external control.
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
LOXL1 (Per-Protocol)
Description
Data represent ratio of total mRNA relative to postmenopausal external control.
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Tropoelastin (Per-Protocol)
Description
Data represent ratio of total mRNA relative to postmenopausal external control.
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
TGFB1 (Per-Protocol)
Description
Data represent ratio of total mRNA relative to postmenopausal external control.
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Title
Vaginal Wall Degradative Activity, Mucosa, MMP-9
Description
Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention
Secondary Outcome Measure Information:
Title
Serum Estrone Levels, Baseline
Time Frame
Baseline
Title
Serum Estrone Levels, Surgery
Time Frame
Time of surgery
Title
Serum Estradiol Levels, Baseline
Time Frame
Baseline
Title
Serum Estradiol Levels, Surgery
Time Frame
Time of surgery
Title
Estimated Blood Loss
Description
Intraoperative estimated blood loss
Time Frame
Time of surgery, i.e. after 6-8 weeks of intervention

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Women, still with uterus, planning total hysterectomy as part of surgical repair for pelvic organ prolapse Symptomatic anterior and/or apical vaginal prolapse greater than or equal to Stage 2 (i.e., bulge extends to at least 1 cm of the hymen or beyond) Women between 1 and 10 years after menopause. Menopause is defined as one year of amenorrhea or surgical ovariectomy. Age 40-70 years old No estrogen replacement therapy in the last 1 month Physically capable of daily application of vaginal cream Exclusion Criteria: BMI >35 Prior surgical repair of prolapse involving the vaginal cuff. Prior total hysterectomy Premenopausal or postmenopausal >10 years Prior steroid hormone replacement therapy of duration >1 month (oral or vaginal estrogen, testosterone or corticosteroids) History of connective tissue disease (Ehlers-Danlos, Marfan, etc) History of vaginal radiation Contraindications for estrogen replacement therapy (current, or history of, spontaneous deep vein thrombosis, stroke, coronary artery disease, breast or endometrial cancer) Concurrent use of steroid cream for treatment of Lichen sclerosis Recent history (within last month) of vaginal infection or vaginitis Current tobacco use
Facility Information:
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24947034
Citation
Rahn DD, Good MM, Roshanravan SM, Shi H, Schaffer JI, Singh RJ, Word RA. Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab. 2014 Oct;99(10):3728-36. doi: 10.1210/jc.2014-1216. Epub 2014 Jun 20.
Results Reference
derived

Learn more about this trial

Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor

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