Pelvic Organ Prolapse
Conditions
Keywords
Pelvic organ prolapse, Pelvic floor physical therapy, Vaginal estrogen, Placebo
Brief summary
This is a randomized controlled trial in which women with symptomatic mild pelvic organ prolapse undergoing Pelvic Floor Physical Therapy (PFPT) receive vaginal estrogen versus placebo to see if a combined approach to treatment leads to improvement in clinical outcomes. The investigators predict that PFPT in combination with vaginal estrogen will lead to decreased pelvic floor symptoms and improved anatomical support corroborated by biomarker data.
Detailed description
The pathogenesis of pelvic organ prolapse (POP) is unknown. Few studies have correlated patient symptoms and amount of prolapse with biomarkers. POP has traditionally been managed with a pessary or surgery. Recent studies suggest a reduction in POP symptoms following Pelvic Floor Physical Therapy (PFPT). Vaginally delivered hormones are also commonly used to treat prolapse symptoms, with little evidence supporting a clinical benefit. The investigators hypothesize that the optimal approach to improving prolapse symptoms in the patient with mild prolapse requires re-alignment and strengthening of levator muscles via PFPT, and optimization of tissue integrity via local estrogen therapy. The investigators propose to test this hypothesis in a randomized controlled trial in which women with symptomatic mild prolapse opting for PFPT, receive treatment with PFPT in combination with vaginal estrogen versus placebo. The investigators predict that the combined approach will lead to decreased symptoms and improved anatomical support corroborated by biomarker data.
Interventions
DRUGVaginal estrogen
1 gram vaginally for 7 days, followed by 1 gram vaginally twice weekly thereafter
DRUGPlacebo
1 gram vaginally for 7 days, followed by 1 gram vaginally twice weekly thereafter
Sponsors
American Urogynecologic Society
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Pfizer
Pamela Moalli
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Women in good health aged 40-80 * Has symptoms of pelvic organ prolapse; answers yes to at least 1 of the following questions: Do you feel or see a vaginal bulge? Do you feel pressure in the vagina? * Meets POP-Q criteria on exam for stage I, II, or III prolapse * Interested in PFPT for management of POP * Normal mammogram within 1 year of enrollment
Exclusion criteria
* Prior surgery for prolapse or incontinence * Other prior interventions for prolapse (e.g. pessary, PFPT) * Previous bilateral salpingo-oophorectomy (women with 1 ovary will be eligible) * Known liver dysfunction * Connective tissue diseases known to affect collagen or elastin remodeling (including: Lupus, Rheumatoid Arthritis, Scleroderma, Sjogrens syndrome, Marfan syndrome, and Ehlers-Danlos syndrome) * Unevaluated abnormal vaginal bleeding or abnormal pap smear in the previous year * BMI \> 35 kg/m2 * Estrogen therapy (including birth control) in the previous year * Current or prior breast or pelvic malignancy (ovarian, tubal, uterine, cervical or vaginal) * Contraindication to hormone use (i.e. thromboembolic disorder, use of anti-coagulants, coronary artery disease, history of stroke)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Improvement | 6 months after starting vaginal cream | The Patient Global Impression of Improvement (PGI-I) is a global index that may be used to rate the response of a condition to a therapy (transition scale). It is a simple, direct, easy to use scale that is intuitively understandable to clinicians. Potential Responses: 1. Very Much Better 2. Much Better 3. A Little Better 4. No Change 5, A Little Worse 6\. Much Worse 7. Very Much Worse Lower scores indicate more imiprovment / better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pelvic Floor Symptoms | 6 months | Pelvic Floor Symptoms, using the PFDI-20. The Pelvic Floor Distress Inventory is a condition specific quality of life instrument that assesses distress from pelvic organ prolapse, colorectal-anal, and urinary symptoms. Higher scores indicate greater disease burden. Range: 0 to 300 |
| General Quality of Life | 6 months | Quality of Life, using the PFIQ-7 The Pelvic Floor Impact Questionnaire assesses how bladder, bowel, and vaginal symptoms affect activity, relationships, ad feelings. Higher numbers indicate greater disease burden. Score range: 0 to 300 |
| Pelvic Organ Prolapse Stage | 6 months | Pelvic Organ Prolapse Stage, using the POP-Q exam. The Pelvic Organ Prolapse Quantification System use 9 measurements in the vagina to assess prolapse stage. Higher stage indicates greater prolapse. Range: 0 to 4 |
| Collagenase Activity | 6 months | Collagenase Activity, via vaginal swabs collected from the posterior fornix will be used for biochemical analysis. |
| Sexual Function | 6 months | Sexual Function, using the PISQ-12 The Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire evaluates sexual function in patients with incontinence and/or vaginal prolapse. Higher scores indicate greater disease burden. Scale: 0 to 48 |
Countries
United States
Participant flow
Pre-assignment details
One subject was ineligible prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Vaginal Estrogen Patients in the experimental group will receive vaginal estrogen cream
Vaginal estrogen: 1 gram vaginally for 7 days, followed by 1 gram vaginally twice weekly thereafter | 9 |
| Placebo Cream Patients in the comparison group will receive placebo vaginal cream
Placebo: 1 gram vaginally for 7 days, followed by 1 gram vaginally twice weekly thereafter | 11 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo Cream | Total | Vaginal Estrogen |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 17 Participants | 8 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 11 participants | 20 participants | 9 participants |
| Sex: Female, Male Female | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 11 |
| other Total, other adverse events | 0 / 9 | 0 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 11 |
Outcome results
Primary
Patient Global Impression of Improvement
The Patient Global Impression of Improvement (PGI-I) is a global index that may be used to rate the response of a condition to a therapy (transition scale). It is a simple, direct, easy to use scale that is intuitively understandable to clinicians. Potential Responses: 1. Very Much Better 2. Much Better 3. A Little Better 4. No Change 5, A Little Worse 6\. Much Worse 7. Very Much Worse Lower scores indicate more imiprovment / better outcome.
Time frame: 6 months after starting vaginal cream
Population: Subjects who completed surveys at 6 months post treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vaginal Estrogen | Patient Global Impression of Improvement | 2.3 score on a scale |
| Placebo Cream | Patient Global Impression of Improvement | 3.0 score on a scale |
Secondary
Collagenase Activity
Collagenase Activity, via vaginal swabs collected from the posterior fornix will be used for biochemical analysis.
Time frame: 6 months
Population: Data not available. Vaginal swabs were collected from participants. However, the lab was unable to analyze collagenase activity because there was not enough protein isolated from the samples.
Secondary
General Quality of Life
Quality of Life, using the PFIQ-7 The Pelvic Floor Impact Questionnaire assesses how bladder, bowel, and vaginal symptoms affect activity, relationships, ad feelings. Higher numbers indicate greater disease burden. Score range: 0 to 300
Time frame: 6 months
Population: Subjects who completed surveys at 6 months post treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vaginal Estrogen | General Quality of Life | 6.1 score on a scale |
| Placebo Cream | General Quality of Life | 19.9 score on a scale |
Secondary
Pelvic Floor Symptoms
Pelvic Floor Symptoms, using the PFDI-20. The Pelvic Floor Distress Inventory is a condition specific quality of life instrument that assesses distress from pelvic organ prolapse, colorectal-anal, and urinary symptoms. Higher scores indicate greater disease burden. Range: 0 to 300
Time frame: 6 months
Population: Subjects who completed surveys at 6 months post treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vaginal Estrogen | Pelvic Floor Symptoms | 16.9 score on a scale |
| Placebo Cream | Pelvic Floor Symptoms | 48 score on a scale |
Secondary
Pelvic Organ Prolapse Stage
Pelvic Organ Prolapse Stage, using the POP-Q exam. The Pelvic Organ Prolapse Quantification System use 9 measurements in the vagina to assess prolapse stage. Higher stage indicates greater prolapse. Range: 0 to 4
Time frame: 6 months
Population: Subjects who underwent POP-Q measurements at 6 months post treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vaginal Estrogen | Pelvic Organ Prolapse Stage | 2 units on a scale |
| Placebo Cream | Pelvic Organ Prolapse Stage | 2 units on a scale |
Secondary
Sexual Function
Sexual Function, using the PISQ-12 The Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire evaluates sexual function in patients with incontinence and/or vaginal prolapse. Higher scores indicate greater disease burden. Scale: 0 to 48
Time frame: 6 months
Population: Subjects who completed surveys at 6 months post treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vaginal Estrogen | Sexual Function | 12.8 score on a scale |
| Placebo Cream | Sexual Function | 14 score on a scale |