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Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen (IMPROVE)

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ClinicalTrials.gov Identifier: NCT02431897
Recruitment Status : Recruiting
First Posted : May 1, 2015
Last Update Posted : May 1, 2018
Sponsor:
Collaborators:
University of Alabama at Birmingham
Women and Infants Hospital of Rhode Island
Pfizer
Information provided by (Responsible Party):
David Rahn, MD, University of Texas Southwestern Medical Center

Brief Summary:
This study randomizes postmenopausal women with symptomatic pelvic organ prolapse planning native tissue transvaginal surgical repair to 6-8 weeks of preoperative and 1-year continued postoperative vaginal estrogen cream compared to placebo cream. This clinical trial and basic science investigation are designed to understand the mechanisms by which local estrogen treatment affects connective tissues of the pelvic floor and determine whether its use before and after prolapse repair will (i) improve success rates of the surgical intervention and minimize prolapse recurrence and (ii) impact favorably upon symptoms of other pelvic floor disorders.

Condition or disease Intervention/treatment Phase
Pelvic Organ Prolapse Urogenital Prolapse Vaginal Vault Prolapse Cystocele Uterine Prolapse Vaginal Prolapse Pelvic Floor Disorders Drug: Conjugated Estrogens Cream Drug: Placebo Cream Phase 4

Detailed Description:
This is a double-blind randomized trial of intravaginal estrogen (conjugated estrogens, 0.625mg/1g cream) vs. placebo in postmenopausal women (n=222 total) with symptomatic prolapse beyond the hymen planning transvaginal native tissue repairs. Medication will be started 6-8 weeks before surgery and continued for 1 year postoperatively, i.e. until scar remodeling is complete. The investigators aim to determine if pre- and postoperative intravaginal estrogen therapy (i) results in anatomic and patient-reported subjective improvement in pelvic organ support, and (ii) impacts other pelvic floor disorders (overactive bladder and incontinence, sexual function and pain, postoperative cystitis), satisfaction, quality of life, and vaginal wound healing. Finally, (iii) the investigators will determine the potential mechanisms by which local estrogen treatment alters pelvic organ support by examining full-thickness vaginal wall biopsies taken at the time of surgery for histologic, connective tissue, and smooth muscle synthesis and degradative changes. The investigators expect this will highlight other novel targets for future therapies in prolapse repair and prevention.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 222 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen
Study Start Date : December 2016
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Estrogen Cream Drug: Conjugated Estrogens Cream
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 6-8 weeks before surgery, then 2x/week for 1 year after surgery.
Other Name: Premarin Vaginal Cream

Placebo Comparator: Placebo Cream Drug: Placebo Cream
1g applied vaginally nightly for 2 weeks then 2x/week for 6-8 weeks before surgery, then 2x/week for 1 year after surgery.




Primary Outcome Measures :
  1. Surgical "success" or "failure" defined by (i) anatomic assessment of prolapse, (ii) presence or absence of bulge symptoms, (iii) retreatment of prolapse [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Condition specific (i.e. pelvic organ prolapse) quality of life as measured by Pelvic Floor Distress Inventory-20 (PFDI-20) questionnaire [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months

  2. Condition specific (i.e. pelvic organ prolapse) quality of life as measured by Pelvic Floor Impact Questionnaire-7 (PFIQ-7) [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months

  3. Generic quality of life as measured by SF-12 questionnaire [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months

  4. Urinary symptoms as measured by urinary subscale questions of the Pelvic Floor Distress Inventory-20 (PFDI-20) questionnaire, i.e. the Urinary Distress Inventory, UDI-6 [ Time Frame: Baseline, time of surgery (8 wk) ]
    Change in questionnaire scores from baseline to time of surgery

  5. Urinary symptoms as measured by urinary subscale questions of the Pelvic Floor Distress Inventory-20 (PFDI-20) questionnaire, i.e. the Urinary Distress Inventory, UDI-6 [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months

  6. Urinary symptoms as measured by urinary subscale questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire [ Time Frame: Baseline, time of surgery (8 wk) ]
    Change in questionnaire scores from baseline to time of surgery

  7. Urinary symptoms as measured by urinary subscale questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months

  8. Sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) [ Time Frame: Baseline, time of surgery (8 wk) ]
    Change in questionnaire scores from baseline to time of surgery

  9. Sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months

  10. Number of participants with adverse events [ Time Frame: through 12 months ]
    Comparison of proportions by treatment group



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Ages Eligible for Study:   48 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Postmenopausal: no menses for >1 year
  • Minimum age: 48 years
  • Symptomatic apical and/or anterior vaginal wall prolapse, stage 2 or greater
  • No estrogen replacement within the last month (may come off current treatment, i.e. wash out, to join the study)
  • Medically fit for elective surgery
  • Physically able to apply/insert the study drug
  • Available for clinic follow-up for minimum 1yr

Exclusion Criteria:

  • Concurrent use of steroid creams for other indications (e.g. lichen sclerosis)
  • BMI >35 kg/m2
  • Recent history (within last month) of vaginal infection or vaginitis
  • Contraindications to estrogen therapy (e.g. spontaneous DVT, stroke, breast or endometrial/ hormone-responsive cancer, genital bleeding of unknown cause)
  • History of connective tissue disease
  • Any oral or transdermal estrogen, SERM, or other medication impacting vaginal milieu
  • History of vaginal irradiation
  • Allergy to Premarin or its constituents
  • Prior apical repair or use of mesh for prolapse repair
  • Current tobacco use

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02431897


Contacts
Contact: David D Rahn, MD 214-648-6430 david.rahn@utsouthwestern.edu
Contact: Agnes Burris, RN 214-645-3833 agnes.burris@utsouthwestern.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35249
Contact: Holly E Richter, PhD, MD       hrichter@uabmc.edu   
Contact: Robin Willingham, RN, BSN    205-934-3904    rwillingham@uabmc.edu   
United States, Rhode Island
Women & Infants Hospital of Rhode Island Recruiting
Providence, Rhode Island, United States, 02905
Contact: Vivan W Sung, MD, MPH       vsung@wihri.org   
Contact: Ann Meers, RN, CCRC    401-276-4869    ameers@wihri.org   
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: David D Rahn, MD    214-648-6430    David.Rahn@UTSouthwestern.edu   
Contact: Agnes Burris, RN    214-645-3833    Agnes.Burris@UTSouthwestern.edu   
Principal Investigator: David D Rahn, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
University of Alabama at Birmingham
Women and Infants Hospital of Rhode Island
Pfizer
Investigators
Principal Investigator: David D Rahn, MD University of Texas Southwestern Medical Center

Responsible Party: David Rahn, MD, Associate Professor, Dept. of Obstetrics & Gynecology, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT02431897     History of Changes
Other Study ID Numbers: AG047290-01
First Posted: May 1, 2015    Key Record Dates
Last Update Posted: May 1, 2018
Last Verified: April 2018

Keywords provided by David Rahn, MD, University of Texas Southwestern Medical Center:
Pelvic Organ Prolapse
Pelvic Floor Disorders
Therapy, Estrogen Replacement
Estrogens, Conjugated

Additional relevant MeSH terms:
Estrogens
Estrogens, Conjugated (USP)
Recurrence
Prolapse
Pelvic Organ Prolapse
Pelvic Floor Disorders
Cystocele
Uterine Prolapse
Disease Attributes
Pathologic Processes
Pathological Conditions, Anatomical
Pregnancy Complications
Urinary Bladder Diseases
Urologic Diseases
Uterine Diseases
Genital Diseases, Female
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs