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

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ClinicalTrials.gov Identifier: NCT01778985
Recruitment Status : Completed
First Posted : January 29, 2013
Results First Posted : September 10, 2014
Last Update Posted : October 2, 2014
Sponsor:
Collaborator:
American Urogynecologic Society Foundation Astellas Research Award
Information provided by (Responsible Party):
David Rahn, MD, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE January 23, 2013
First Posted Date  ICMJE January 29, 2013
Results First Submitted Date  ICMJE May 20, 2014
Results First Posted Date  ICMJE September 10, 2014
Last Update Posted Date October 2, 2014
Study Start Date  ICMJE December 2012
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2014)
  • Vaginal Wall Composition: Epithelium (Intention to Treat) [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ]
    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 ]
    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 ]
    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 ]
    Will assess vaginal wall histology - thicknesses of muscularis
  • hCOL1A1, Per-Protocol [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
Original Primary Outcome Measures  ICMJE
 (submitted: January 25, 2013)
  • Vaginal wall composition [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ]
    Will assess vaginal wall histology - relative thicknesses of epithelium, lamina propria, and muscularis; description of elastic fiber morphology
  • Vaginal wall elastic fiber and collagen: synthesis [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ]
    Will assess mRNA levels of collagen I and III, lysyl oxidase (LOX), LOXL1, tropoelastin, and TGF beta
  • Vaginal wall collagen: synthesis [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ]
    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 ]
    Will assess zymograms for matrix metalloprotease (MMP) 2 and 9 activity
  • Vaginal wall elastic fiber: synthesis [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ]
    Will assess western blots for assessment of amounts of lysyl oxidase and fibulin-5 proteins
Change History Complete list of historical versions of study NCT01778985 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2014)
  • Serum Estrone Levels, Baseline [ Time Frame: Baseline ]
  • Serum Estrone Levels, Surgery [ Time Frame: Time of surgery ]
  • Serum Estradiol Levels, Baseline [ Time Frame: Baseline ]
  • Serum Estradiol Levels, Surgery [ Time Frame: Time of surgery ]
  • Estimated Blood Loss [ Time Frame: Time of surgery, i.e. after 6-8 weeks of intervention ]
    Intraoperative estimated blood loss
Original Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2013)
Serum and vaginal mucosa estrone and estradiol levels [ Time Frame: Before and after 6-8 weeks of intervention ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
Official Title  ICMJE Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE
  • Pelvic Organ Prolapse
  • Menopause
Intervention  ICMJE
  • Drug: Premarin
    Other Name: Conjugated equine estrogen
  • Other: Placebo
    Other Name: Placebo cream
Study Arms  ICMJE
  • 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
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 25, 2013)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2013
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 40 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01778985
Other Study ID Numbers  ICMJE STU-042011-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party David Rahn, MD, University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE American Urogynecologic Society Foundation Astellas Research Award
Investigators  ICMJE Not Provided
PRS Account University of Texas Southwestern Medical Center
Verification Date September 2014

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