Pelvic Organ ProlapsePhase 4PETNCT01778985

Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor

A Phase 4 study testing Premarin in people with Pelvic Organ Prolapse and Menopause, run by University of Texas Southwestern Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 to 70 years, women onlyHealthy volunteers can take part
Conditions the study is for: Pelvic Organ Prolapse, Menopause
What is being tested?: Premarin
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 30 participants
Where: 1 siteUnited States
Study dates: Dec 2012to Apr 2013
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 70 years
Women only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Show all 11Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Texas Southwestern Medical Center
Dallas, Texas, 75390

Other trials in United States

About this study

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.

Conditions: Pelvic Organ Prolapse, Menopause
Being tested: Premarin, Placebo
Keywords: Pelvic organ prolapse, Menopause, Estrogen, Premarin
Medical subject headings: Pelvic Organ Prolapse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PremarinDrug
Also called Conjugated equine estrogen
PlaceboOther
Also called Placebo cream

Study groups in NCT01778985
Study group	Role	What they receive
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. Receives: Drug: Premarin
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. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Vaginal Wall Composition: Epithelium (Intention to Treat)
Will assess vaginal wall histology - thicknesses of epithelium
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: Time of surgery, i.e. 6-8 weeks of intervention
hCOL3, (Per-Protocol)
Data represent ratio of total mRNA relative to postmenopausal external control.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Time of surgery, i.e. after 6-8 weeks of intervention

Secondary outcomes (5)

Serum Estrone Levels, Baseline
Measured: Baseline
Serum Estrone Levels, Surgery
Measured: Time of surgery
Serum Estradiol Levels, Baseline
Measured: Baseline
Serum Estradiol Levels, Surgery
Measured: Time of surgery
Estimated Blood Loss
Intraoperative estimated blood loss
Measured: Time of surgery, i.e. after 6-8 weeks of intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2012Apr 2013

First posted29 Jan 2013 (estimated)
Study startDec 2012
Primary completionMar 2013
Study completionApr 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pelvic Organ ProlapseStudies of the same condition, open and under way.
More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01778985
Sponsor's protocol ID: STU-042011-101
Acronym: PET
Status last verified: Sep 2014
First submitted: 23 Jan 2013
Last updated: 2 Oct 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 24947034

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Recruiting
Safety and Performance of a Pelvic Floor Mesh Implant for Laparoscopic Sacrocolpopexy (ProGYNious)
Pelvic Organ Prolapse (POP), Synthetic Mesh
Recruiting
Pelvic Floor Muscle Training During Pregnancy
Urinary Incontinence, Anal Incontinence
Not yet recruiting
Perineal Protection Device for Reducing Perineal Trauma During Vaginal Delivery in First-time Mothers: a Multicenter Randomized Controlled Trial
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All Pelvic Organ Prolapse trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
ClinicalTrials.gov ID: NCT01778985
Acronym / sponsor ID: PET / STU-042011-101
Conditions: Pelvic Organ Prolapse, Menopause
Keywords: Pelvic organ prolapse, Menopause, Estrogen, Premarin
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: University of Texas Southwestern Medical CenterUniversity, hospital or other
Collaborators: American Urogynecologic Society Foundation Astellas Research Award
Study start: Dec 2012
Primary completion: Mar 2013 (actual)
Study completion: Apr 2013 (actual)
First posted: 29 Jan 2013 (estimated)
Results: Posted 10 Sep 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Premarin	Experimental	Drug: PremarinPremarin 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	Other: PlaceboPlacebo 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.

Who may qualify

Ages: 40 to 70 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (11 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PremarinAlso: Conjugated equine estrogen	Drug	Premarin
PlaceboAlso: Placebo cream	Other	Placebo

Primary outcome

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

5 secondary outcomes

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

Results and safety

Results posted to the registry on 10 Sep 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Premarin	15	8
Placebo	15	12

Primary outcome: Vaginal Wall Composition: Epithelium (Intention to Treat)

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention. Mean (Standard Error). Unit: microns

Measure	Premarin n = 12	Placebo n = 12
Value	413.9 (63.7)	314.1 (42.6)

Premarin vs Placebo: p = 0.21, t-test, 2 sided

Population analysed: Patients completing surgery with biopsy specimens available for analysis ("intention to treat")

Primary outcome: Vaginal Wall Composition: Epithelium (Per-Protocol)

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention. Mean (Standard Error). Unit: microns

Measure	Premarin n = 8	Placebo n = 12
Value	550.5 (45.1)	314.1 (42.6)

Premarin vs Placebo: p = 0.002, t-test, 2 sided

Population analysed: Patients completing surgery with biopsy specimens available for analysis and who were adherent to study medication ("per protocol")

Primary outcome: Vaginal Wall Composition: Muscularis (Intention to Treat)

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention. Mean (Standard Error). Unit: microns

Measure	Premarin n = 12	Placebo n = 12
Value	5670.4 (2154.7)	2807.1 (622.5)

Premarin vs Placebo: p = 0.22, t-test, 2 sided

Population analysed: Patients completing surgery with biopsy specimens available for analysis ("intention to treat")

Primary outcome: Vaginal Wall Composition: Muscularis (Per-Protocol)

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention. Mean (Standard Error). Unit: microns

Measure	Premarin n = 8	Placebo n = 12
Value	7570.7 (3193.1)	2807.1 (622.5)

Premarin vs Placebo: p = 0.088, t-test, 2 sided

Population analysed: Patients completing surgery with biopsy specimens available for analysis and who were adherent to study medication ("per protocol")

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 - 8 weeks of preoperative use of vaginal estrogen (vs placebo) cream. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Premarin	0 of 15 (0%)	3 of 15 (20%)	Not reported
Placebo	0 of 15 (0%)	0 of 15 (0%)	Not reported

Limitations and caveats (from the sponsor): 4 patients nonadherent to study protocol in the Premarin arm.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24947034Rahn 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.

Related trials for Pelvic Organ Prolapse

Active, not recruitingObservational study
Return to Physical Activity After Retropublic Transvaginal Sling and Laparoscopic Sacrocolpopexy
Stress Urinary Incontinence, Pelvic Organ Prolapse
Active, not recruitingObservational study
i-Stitch for Bilateral Sacrospinous Ligament Fixation (SSLF)
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Recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Premarin in people with Pelvic Organ Prolapse and Menopause, run by University of Texas Southwestern Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Vaginal Wall Composition: Epithelium (Intention to Treat) (time frame: Time of surgery, i.e. after 6-8 weeks of intervention). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01778985, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2014.