Endometriosis
Conditions
Keywords
resveratrol
Brief summary
This study aims to verify whether the use of 40 mg of resveratrol per day associated with monophasic contraceptive pill (levonorgestrel 0.15mg/ethinyl estradiol 0.03mg) reduces pelvic pain at the end of 2 months of treatment, compared to the use of the pill with placebo.
Detailed description
Endometriosis is a disease that affects 176 million women around the world, and it is present in about 60% of adolescent women with chronic pelvic pain and dysmenorrhea. Some researchers have investigated the antiproliferative effect of resveratrol in endometriosis using animal models and humans. The reduction in the size and activity of the endometriotic implants has been observed with the use of resveratrol. The reduction of pain in patients with endometriosis is an important aspect of the quality of life. The use of a medication with few side effects and the lack of clinical quality trials justify this study, which aims to verify whether the use of 40 mg of resveratrol per day associated with monophasic contraceptive pill reduces pelvic pain at the end of 2 months of treatment, compared to the use of the pill with placebo. This study will be randomized, prospective, double blind with two arms of 22 patients; the CONSORT parameters will be followed. The degree of pain by visual analog scale, prolactin levels (ng / mL) and the carcinoembryonic antigen levels (CA125) (IU / L) will be measured at the begging and at the end of trial. These parameters will be the outcomes.
Interventions
DRUGPlacebo
40mg of starch
DRUGResveratrol
40mg of resveratrol (powder)
Sponsors
Hospital de Clinicas de Porto Alegre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Endometriosis diagnosed by laparoscopy
Exclusion criteria
* Known allergy to resveratrol * Use of gonadotropin or danazol in the last month
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Scores Measured by VAS (Visual Analog Scale) at Day 42. | 42 days | Pain will be measured by VAS (visual analog scale) as baseline and at the end of the study, considering the last 7 days. VAS was used to measuring pain intensity, ranging continuously from 0 (no pain) to 10 (worst imaginable pain). The main outcome compared median pain levels between both arms on day 42. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum CA125 Levels at 42 Days | 42 days | Serum levels of CA125 will be measured after 42 days of treatment in UI/mL. Median levels of CA125 were compared between both groups on day 42, and to baseline values (day 1). |
| Serum Prolactin Levels at 42 Days | 42 days | Serum levels of prolactin will be measured after 42 days of treatment. Median levels of prolactin were compared between both groups on day 42. |
Countries
Brazil
Participant flow
Recruitment details
Between June 18th and November 6th, 2015, 234 women with diagnosis of endometriosis were screened for the study at outpatient clinic of Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Participants by arm
| Arm | Count |
|---|---|
| Resveratrol Patients will take once a day a monophasic pill (ethinylestradiol + levonorgestrel) continuously for 42 days with 40mg of resveratrol
Resveratrol: 40mg of resveratrol (powder) | 22 |
| Placebo Patients will take once a day a monophasic pill (ethinylestradiol + levonorgestrel) continuously for 42 days with 1 pill of placebo (starch)
Placebo: 40mg of starch | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Intense Menstrual bleeding | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Resveratrol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 35.4 years STANDARD_DEVIATION 7.1 | 32.4 years STANDARD_DEVIATION 7 | 33.9 years STANDARD_DEVIATION 7.1 |
| Baseline pain levels (Visual Analog Scale - VAS) day 1 | 5.4 units on a scale STANDARD_DEVIATION 2.6 | 5.7 units on a scale STANDARD_DEVIATION 2 | 5.6 units on a scale STANDARD_DEVIATION 2.3 |
| CA-125 | 14.1 UI/mL | 18.7 UI/mL | 17.04 UI/mL |
| Prolactin | 12.65 ng/mL STANDARD_DEVIATION 5.9 | 14.27 ng/mL STANDARD_DEVIATION 6.6 | 13.13 ng/mL STANDARD_DEVIATION 6.5 |
| Race/Ethnicity, Customized black | 6 participants | 7 participants | 13 participants |
| Race/Ethnicity, Customized white | 16 participants | 15 participants | 31 participants |
| Region of Enrollment Brazil | 22 participants | 22 participants | 44 participants |
| Sex: Female, Male Female | 22 Participants | 22 Participants | 44 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 | — / — | — / — |
| other Total, other adverse events | 10 / 22 | 13 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Pain Scores Measured by VAS (Visual Analog Scale) at Day 42.
Pain will be measured by VAS (visual analog scale) as baseline and at the end of the study, considering the last 7 days. VAS was used to measuring pain intensity, ranging continuously from 0 (no pain) to 10 (worst imaginable pain). The main outcome compared median pain levels between both arms on day 42.
Time frame: 42 days
Population: Intention to treat analysis, patients who were lost on follow-up had their last registry on pain values or plasma levels measurements repeated in the following consultations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Resveratrol | Pain Scores Measured by VAS (Visual Analog Scale) at Day 42. | 3.2 units on a scale |
| Placebo | Pain Scores Measured by VAS (Visual Analog Scale) at Day 42. | 3.9 units on a scale |
Comparison: A sample size of at least 21 patients per arm would be necessary to have a 90% chance of detecting, as significant at the 1% level, a difference of 3 points in a scale of 10 points, between both groups as the primary outcome, after 42 days of treatment.p-value: 0.7Mann-Whitney test
Secondary
Serum CA125 Levels at 42 Days
Serum levels of CA125 will be measured after 42 days of treatment in UI/mL. Median levels of CA125 were compared between both groups on day 42, and to baseline values (day 1).
Time frame: 42 days
Population: One of subjects from the placebo group decided to leave the study after randomization, thus the n = 21 in the CA125 levels.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Resveratrol | Serum CA125 Levels at 42 Days | 11.7 UI/mL |
| Placebo | Serum CA125 Levels at 42 Days | 13.7 UI/mL |
p-value: 0.1Mann-Whitney test
Secondary
Serum Prolactin Levels at 42 Days
Serum levels of prolactin will be measured after 42 days of treatment. Median levels of prolactin were compared between both groups on day 42.
Time frame: 42 days
Population: one of the subjects in the placebo group decided to leave the study after randomization, thus n = 21
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Resveratrol | Serum Prolactin Levels at 42 Days | 12 ng/mL |
| Placebo | Serum Prolactin Levels at 42 Days | 11.1 ng/mL |
p-value: 0.8Mann-Whitney test