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| Name | Class |
|---|---|
| American Urogynecologic Society Foundation Astellas Research Award | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Premarin | Experimental | 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 | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Premarin | Drug |
|
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Vaginal Wall Composition: Epithelium (Intention to Treat) | Will assess vaginal wall histology - thicknesses of epithelium | Time of surgery, i.e. after 6-8 weeks of intervention |
| Vaginal Wall Composition: Epithelium (Per-Protocol) | Will assess vaginal wall histology - thicknesses of epithelium | Time of surgery, i.e. after 6-8 weeks of intervention |
| Vaginal Wall Composition: Muscularis (Intention to Treat) | Will assess vaginal wall histology - thicknesses of muscularis | Time of surgery, i.e. after 6-8 weeks of intervention |
| Vaginal Wall Composition: Muscularis (Per-Protocol) | Will assess vaginal wall histology - thicknesses of muscularis | Time of surgery, i.e. after 6-8 weeks of intervention |
| hCOL1A1, Per-Protocol | Data represent ratio of total mRNA relative to postmenopausal external control. | Time of surgery, i.e. after 6-8 weeks of intervention |
| Total Collagen Content in Vaginal Muscularis, (Per-Protocol) | Will assess hydroxy-proline assays as index of amount of collagen | Time of surgery, i.e. after 6-8 weeks of intervention |
| Vaginal Wall Degradative Activity, Muscularis, MMP-9 | Will assess zymograms for total matrix metalloprotease (MMP) 9 activity |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Estrone Levels, Baseline | Baseline | |
| Serum Estrone Levels, Surgery | Time of surgery | |
| Serum Estradiol Levels, Baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24947034 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Premarin | 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. Premarin |
| FG001 | Placebo | 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. Placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Premarin | 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. Premarin |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Vaginal Wall Composition: Epithelium (Intention to Treat) | Will assess vaginal wall histology - thicknesses of epithelium | Patients completing surgery with biopsy specimens available for analysis ("intention to treat") | Mean | Standard Error | microns | Time of surgery, i.e. after 6-8 weeks of intervention |
|
6 - 8 weeks of preoperative use of vaginal estrogen (vs placebo) cream
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Premarin | 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. Premarin |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vulvovaginal pain | Reproductive system and breast disorders | Systematic Assessment |
4 patients nonadherent to study protocol in the Premarin arm.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David D. Rahn, M.D. | University of Texas Southwestern Medical Center | 214-648-6430 | david.rahn@utsouthwestern.edu |
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| ID | Term |
|---|---|
| D056887 | Pelvic Organ Prolapse |
| ID | Term |
|---|---|
| D011391 | Prolapse |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D004966 | Estrogens, Conjugated (USP) |
| ID | Term |
|---|---|
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
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| Other |
|
|
| Time of surgery, i.e. after 6-8 weeks of intervention |
| Vaginal Wall Composition: Lamina Propria (Intention to Treat) | Will assess vaginal wall histology - thickness of lamina propria. | Time of surgery, i.e. after 6-8 weeks of intervention |
| Vaginal Wall Composition: Lamina Propria (Per-Protocol) | Will assess vaginal wall histology - thickness of lamina propria | Time of surgery, i.e. 6-8 weeks of intervention |
| hCOL3, (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Time of surgery, i.e. after 6-8 weeks of intervention |
| Lysyl Oxidase (LOX) (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Time of surgery, i.e. after 6-8 weeks of intervention |
| LOXL1 (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Time of surgery, i.e. after 6-8 weeks of intervention |
| Tropoelastin (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Time of surgery, i.e. after 6-8 weeks of intervention |
| TGFB1 (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Time of surgery, i.e. after 6-8 weeks of intervention |
| Vaginal Wall Degradative Activity, Mucosa, MMP-9 | Will assess zymograms for total matrix metalloprotease (MMP) 9 activity | Time of surgery, i.e. after 6-8 weeks of intervention |
| Baseline |
| Serum Estradiol Levels, Surgery | Time of surgery |
| Estimated Blood Loss | Intraoperative estimated blood loss | Time of surgery, i.e. after 6-8 weeks of intervention |
| Protocol Violation |
|
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.
Placebo
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Parity | Median | Inter-Quartile Range | deliveries |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
|
|
|
| Primary | Vaginal Wall Composition: Epithelium (Per-Protocol) | Will assess vaginal wall histology - thicknesses of epithelium | Patients completing surgery with biopsy specimens available for analysis and who were adherent to study medication ("per protocol") | Mean | Standard Error | microns | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | Vaginal Wall Composition: Muscularis (Intention to Treat) | Will assess vaginal wall histology - thicknesses of muscularis | Patients completing surgery with biopsy specimens available for analysis ("intention to treat") | Mean | Standard Error | microns | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | Vaginal Wall Composition: Muscularis (Per-Protocol) | Will assess vaginal wall histology - thicknesses of muscularis | Patients completing surgery with biopsy specimens available for analysis and who were adherent to study medication ("per protocol") | Mean | Standard Error | microns | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | hCOL1A1, Per-Protocol | Data represent ratio of total mRNA relative to postmenopausal external control. | Patients completing surgery with biopsy specimens available for analysis and who were adherent to study medication ("per protocol") | Median | Inter-Quartile Range | ratio | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Secondary | Serum Estrone Levels, Baseline | Mean | Standard Error | pg/mL | Baseline |
|
|
|
|
| Primary | Total Collagen Content in Vaginal Muscularis, (Per-Protocol) | Will assess hydroxy-proline assays as index of amount of collagen | Patients completing surgery with biopsy specimens available for analysis and who were adherent to study medication ("per protocol") | Mean | Standard Error | mg collagen per mg muscularis wet weight | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | Vaginal Wall Degradative Activity, Muscularis, MMP-9 | Will assess zymograms for total matrix metalloprotease (MMP) 9 activity | All specimens with sufficient amount of tissue available for zymography analysis were used. | Mean | Standard Error | Relative Units/mg protein | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Secondary | Serum Estrone Levels, Surgery | Mean | Standard Error | pg/mL | Time of surgery |
|
|
|
|
| Secondary | Serum Estradiol Levels, Baseline | Mean | Standard Error | pg/mL | Baseline |
|
|
|
|
| Secondary | Serum Estradiol Levels, Surgery | Mean | Standard Error | pg/mL | Time of surgery |
|
|
|
|
| Primary | Vaginal Wall Composition: Lamina Propria (Intention to Treat) | Will assess vaginal wall histology - thickness of lamina propria. | Mean | Standard Error | microns | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | Vaginal Wall Composition: Lamina Propria (Per-Protocol) | Will assess vaginal wall histology - thickness of lamina propria | Mean | Standard Error | microns | Time of surgery, i.e. 6-8 weeks of intervention |
|
|
|
|
| Primary | hCOL3, (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Median | Inter-Quartile Range | ratio | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | Lysyl Oxidase (LOX) (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Mean | Standard Error | ratio | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | LOXL1 (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Mean | Standard Error | ratio | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | Tropoelastin (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Mean | Standard Error | ratio | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | TGFB1 (Per-Protocol) | Data represent ratio of total mRNA relative to postmenopausal external control. | Mean | Standard Error | ratio | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Primary | Vaginal Wall Degradative Activity, Mucosa, MMP-9 | Will assess zymograms for total matrix metalloprotease (MMP) 9 activity | All specimens with sufficient amount of tissue available for zymography analysis were used. | Mean | Standard Error | Relative Units/mg protein | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| Secondary | Estimated Blood Loss | Intraoperative estimated blood loss | In both study arms, 13 participants did undergo surgery and, therefore, had an estimated blood loss value available for analysis. However, one patient each from both study arms did not have biopsies taken (technical considerations/ intraoperative decision or conversion from total to supracervical hysterectomy without ability to collect biopsy). | Mean | Standard Deviation | mL | Time of surgery, i.e. after 6-8 weeks of intervention |
|
|
|
|
| 0 |
| 15 |
| 3 |
| 15 |
| EG001 | Placebo | 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. Placebo | 0 | 15 | 0 | 15 |
| Annoyance with cream use | Reproductive system and breast disorders | Systematic Assessment |
|
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| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |