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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| placebo | Placebo Comparator | Patients will take once a day a monophasic pill (ethinylestradiol + levonorgestrel) continuously for 42 days with 1 pill of placebo (starch) |
|
| resveratrol | Experimental | Patients will take once a day a monophasic pill (ethinylestradiol + levonorgestrel) continuously for 42 days with 40mg of resveratrol |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | 40mg of starch |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 42 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 42 days |
| Serum Prolactin Levels at 42 Days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ricardo F Savaris, MD, PhD | Hospital de ClÃnicas de Porto Alegre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HCPA | Porto Alegre | Rio Grande do Sul | 90035-903 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23528916 | Result | Johnson NP, Hummelshoj L; World Endometriosis Society Montpellier Consortium. Consensus on current management of endometriosis. Hum Reprod. 2013 Jun;28(6):1552-68. doi: 10.1093/humrep/det050. Epub 2013 Mar 25. | |
| 24604232 | Result | Amaya SC, Savaris RF, Filipovic CJ, Wise JD, Hestermann E, Young SL, Lessey BA. Resveratrol and endometrium: a closer look at an active ingredient of red wine using in vivo and in vitro models. Reprod Sci. 2014 Nov;21(11):1362-9. doi: 10.1177/1933719114525271. Epub 2014 Mar 6. |
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Between June 18th and November 6th, 2015, 234 women with diagnosis of endometriosis were screened for the study at outpatient clinic of Hospital de ClÃnicas de Porto Alegre, Porto Alegre, RS, Brazil
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Median | Full Range | units on a scale | 42 days |
|
42 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| headache | Nervous system disorders | MedDRA 10.0 | Systematic Assessment | 6 cases of mild headache |
There were only 42 days of treatment observed, a longer follow-up, for instance 6 months, may impact the results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ricardo Francalacci Savaris | Hospital de ClÃnicas de Porto Alegre, RS | +55 51 33598653 | rsavaris@hcpa.edu.br |
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| ID | Term |
|---|---|
| D004715 | Endometriosis |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D013213 | Starch |
| D000077185 | Resveratrol |
| ID | Term |
|---|---|
| D005936 | Glucans |
| D001704 | Biopolymers |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
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| Resveratrol |
| Drug |
40mg of resveratrol (powder) |
|
Serum levels of prolactin will be measured after 42 days of treatment. Median levels of prolactin were compared between both groups on day 42.
| 42 days |
| 23091400 | Result | Maia H Jr, Haddad C, Pinheiro N, Casoy J. Advantages of the association of resveratrol with oral contraceptives for management of endometriosis-related pain. Int J Womens Health. 2012;4:543-9. doi: 10.2147/IJWH.S36825. Epub 2012 Oct 10. |
| Intense Menstrual bleeding |
|
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
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Baseline pain levels (Visual Analog Scale - VAS) day 1 | A 10 cm slide ruler, marked at regular intervals in millimeters, was used for measuring pain intensity on a Visual Analog Scale. The scale had scores ranging continuously from 0 (no pain) to 10 (worst imaginable pain). | Mean | Standard Deviation | units on a scale |
|
| CA-125 | Median | Full Range | UI/mL |
|
| Prolactin | Mean | Standard Deviation | ng/mL |
|
| OG001 |
| 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 |
|
|
|
| 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). | One of subjects from the placebo group decided to leave the study after randomization, thus the n = 21 in the CA125 levels. | Posted | Median | Full Range | UI/mL | 42 days |
|
|
|
|
| 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. | one of the subjects in the placebo group decided to leave the study after randomization, thus n = 21 | Posted | Median | Full Range | ng/mL | 42 days |
|
|
|
|
| 0 |
| 22 |
| 10 |
| 22 |
| EG001 | 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) | 0 | 22 | 13 | 22 |
|
| Diplopia | Eye disorders | MedDRA 10.0 | Systematic Assessment |
|
| Reduced libido | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| breast tenderness | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
| Hot flushes | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Increased uterine bleeding | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
| candidiasis | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
| dispareunia | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
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| D000091662 | Genital Diseases |
| D004040 |
| Dietary Carbohydrates |
| D002241 | Carbohydrates |
| D011134 | Polysaccharides |
| D000081225 | Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D059808 | Polyphenols |
| D010636 | Phenols |