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

This study has been completed.
Sponsor:
Collaborator:
American Urogynecologic Society Foundation Astellas Research Award
Information provided by (Responsible Party):
David Rahn, MD, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01778985
First received: January 23, 2013
Last updated: September 9, 2014
Last verified: September 2014

January 23, 2013
September 9, 2014
December 2012
March 2013   (final data collection date for primary outcome measure)
  • Vaginal Wall Composition: Epithelium (Intention to Treat) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess vaginal wall histology - thicknesses of epithelium
  • Vaginal Wall Composition: Epithelium (Per-Protocol) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess vaginal wall histology - thicknesses of epithelium
  • Vaginal Wall Composition: Muscularis (Intention to Treat) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess vaginal wall histology - thicknesses of muscularis
  • Vaginal Wall Composition: Muscularis (Per-Protocol) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess vaginal wall histology - thicknesses of muscularis
  • hCOL1A1, Per-Protocol [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Data represent ratio of total mRNA relative to postmenopausal external control.
  • Total Collagen Content in Vaginal Muscularis, (Per-Protocol) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess hydroxy-proline assays as index of amount of collagen
  • Vaginal Wall Degradative Activity, Muscularis, MMP-9 [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
  • Vaginal Wall Composition: Lamina Propria (Intention to Treat) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess vaginal wall histology - thickness of lamina propria.
  • Vaginal Wall Composition: Lamina Propria (Per-Protocol) [ Time Frame: Time of surgery, i.e. 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess vaginal wall histology - thickness of lamina propria
  • hCOL3, (Per-Protocol) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Data represent ratio of total mRNA relative to postmenopausal external control.
  • Lysyl Oxidase (LOX) (Per-Protocol) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Data represent ratio of total mRNA relative to postmenopausal external control.
  • LOXL1 (Per-Protocol) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Data represent ratio of total mRNA relative to postmenopausal external control.
  • Tropoelastin (Per-Protocol) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Data represent ratio of total mRNA relative to postmenopausal external control.
  • TGFB1 (Per-Protocol) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Data represent ratio of total mRNA relative to postmenopausal external control.
  • Vaginal Wall Degradative Activity, Mucosa, MMP-9 [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
  • Vaginal wall elastic fiber and collagen: synthesis [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess mRNA levels of collagen I and III, lysyl oxidase (LOX), LOXL1, tropoelastin, and TGF beta
  • Vaginal wall composition [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess vaginal wall histology - relative thicknesses of epithelium, lamina propria, and muscularis; description of elastic fiber morphology
  • Vaginal wall elastic fiber: synthesis [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess western blots for assessment of amounts of lysyl oxidase and fibulin-5 proteins
  • Vaginal wall collagen: synthesis [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess hydroxy-proline assays as index of amount of collagen
  • Vaginal wall elastic fiber and collagen: degradative activity [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Will assess zymograms for matrix metalloprotease (MMP) 2 and 9 activity
Complete list of historical versions of study NCT01778985 on ClinicalTrials.gov Archive Site
  • Serum Estrone Levels, Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Serum Estrone Levels, Surgery [ Time Frame: Time of surgery ] [ Designated as safety issue: No ]
  • Serum Estradiol Levels, Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Serum Estradiol Levels, Surgery [ Time Frame: Time of surgery ] [ Designated as safety issue: No ]
  • Estimated Blood Loss [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
    Intraoperative estimated blood loss
Serum and vaginal mucosa estrone and estradiol levels [ Time Frame: Before and after 6-8 weeks of intervention ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
  • Pelvic Organ Prolapse
  • Menopause
  • Drug: Premarin
    Other Name: Conjugated equine estrogen
  • Other: Placebo
    Other Name: Placebo cream
  • Experimental: 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.
    Intervention: Drug: Premarin
  • Placebo Comparator: 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.
    Intervention: Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
April 2013
March 2013   (final data collection date for primary outcome measure)

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
Female
40 Years to 70 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01778985
STU-042011-101
No
David Rahn, MD, University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center
American Urogynecologic Society Foundation Astellas Research Award
Not Provided
University of Texas Southwestern Medical Center
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP