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: August 31, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Pelvic Organ Prolapse
Menopause
Drug: Premarin
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Enrollment: 30
Study Start Date: December 2012
Study Completion Date: April 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Premarin
Other Name: Conjugated equine estrogen
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.
Other: Placebo
Other Name: Placebo cream

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01778985

Locations
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
American Urogynecologic Society Foundation Astellas Research Award
  More Information

No publications provided

Responsible Party: David Rahn, MD, Assistant Professor, Dept. of Obstetrics & Gynecology, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01778985     History of Changes
Other Study ID Numbers: STU-042011-101
Study First Received: January 23, 2013
Results First Received: May 20, 2014
Last Updated: August 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:
Pelvic organ prolapse
Menopause
Estrogen
Premarin

Additional relevant MeSH terms:
Prolapse
Pelvic Organ Prolapse
Pathological Conditions, Anatomical
Estrogens
Estrogens, Conjugated (USP)
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014