To evaluate the effectiveness of Silymarin (Livergol) on IL-6 levels and size of endometrioma lesions in women with ovarian endometriosis: a randomized, double-blind placebo-controlled trial
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Protocol summary
Evaluation and comparison of the effect of silymarin tablet (Levergel) on endometrial lesion volume and interleukin-6 inflammatory factor levels in women before and after intervention
Evaluation and comparison of the effectiveness of silymarin tablet (Levergol) on size of endometrioma lesions and interleukin-6 level in women with ovarian endometriosis before and after intervention
Evaluation and comparison of the effecteffectiveness of silymarin tablet (LevergelLevergol) on endometrial lesion volumesize of endometrioma lesions and interleukin-6 inflammatory factor levelslevel in women with ovarian endometriosis before and after intervention
Gynecologists perform in hospitals and offices.
For this purpose, Levergel tablets and placebo are coded by a research center. The lead researcher treats patients in a double-blind manner based on the drug package code. The code for the drug package is recorded on the personal information form and the researcher who completes the information form will not be informed of the type of treatment.
Gynecologists perform in hospitals and offices.
For this purpose, Levergol tablets and placebo are coded by a research center. The lead researcher treats patients in a double-blind manner based on the drug package code. The code for the drug package is recorded on the personal information form and the researcher who completes the information form will not be informed of the type of treatment.
Gynecologists perform in hospitals and offices. For this purpose, LevergelLevergol tablets and placebo are coded by a research center. The lead researcher treats patients in a double-blind manner based on the drug package code. The code for the drug package is recorded on the personal information form and the researcher who completes the information form will not be informed of the type of treatment.
Married Women of Iranian Fertility (15-49)
No chronic disease (diabetes, hypertension, liver and kidney disease, previous venous embolism ...) based on medical records
Endometrioma based on gynecologist's diagnosis according to ultrasound and marker CA125
Be willing to participate in the study
Iranian married women of reproductive age (15-49); with a confirmed diagnosis of ovarian endometriosis via transvaginal ultrasonography performed by a single sonologist and CA125 level;
No chronic disease based on medical records; without taking specific medications or anti-inflammatory supplements with a specified wash-out period for each one
Married WomenIranian married women of Iranian Fertilityreproductive age (15-49); with a confirmed diagnosis of ovarian endometriosis via transvaginal ultrasonography performed by a single sonologist and CA125 level; No chronic disease (diabetes, hypertension, liver and kidney disease, previous venous embolism ...) based on medical records Endometrioma based on gynecologist's diagnosis according to ultrasound and marker CA125 Be willing to participate in the study; without taking specific medications or anti-inflammatory supplements with a specified wash-out period for each one
زنان متأهل در سنین باروری (15-49) ایرانی
عدم ابتلا به بیماری های مزمن (دیابت، فشارخون بالا، بیماری کبد و کلیه، آمبولی وریدی قبلی...) بر اساس پرونده پزشکی
ابتلا به اندومتریوما بر اساس تشخیص متخصص زنان با توجه به سونوگرافی و مارکر CA125
افراد متمایل به شرکت در مطالعه باشند
زنان متاهل ایرانی در سنین باروری (49-15)؛ با تشخیص تایید شده اندومتریوز تخمدان از طریق سونوگرافی ترانس واژینال انجام شده توسط یک سونولوژیست و سطح CA125.
عدم وجود بیماری مزمن بر اساس سوابق پزشکی؛ و عدم مصرف داروهای خاص یا مکمل های ضد التهابی با دوره washout مشخص برای هر یک
زنان متأهلمتاهل ایرانی در سنین باروری (49-15-49) ایرانی؛ با تشخیص تایید شده اندومتریوز تخمدان از طریق سونوگرافی ترانس واژینال انجام شده توسط یک سونولوژیست و سطح CA125. عدم ابتلا بهوجود بیماری های مزمن (دیابت، فشارخون بالا، بیماری کبد و کلیه، آمبولی وریدی قبلی...) بر اساس پروندهسوابق پزشکی ابتلا به اندومتریوما بر اساس تشخیص متخصص زنان؛ و عدم مصرف داروهای خاص یا مکمل های ضد التهابی با توجه به سونوگرافی و مارکر CA125 افراد متمایل به شرکت در مطالعه باشنددوره washout مشخص برای هر یک
Those in the intervention group received Liverpool 140 mg twice daily for three months, and those in the control group received placebo for exactly three months with exactly the same appearance as the Liverpool tablet and with the same order. All people receive this drug along with their usual treatments (which include painkillers such as NSAIDs or a variety of hormonal compounds including estrogen and progesterone (LD tablets)) with the same treatment protocol according to the treatment of endometrial lesions. There is no drug between conventional endometrioma treatment and Liverpool treatment.
All participants in the intervention group will receive a dose of 280 mg silymarin including two tablets of Livergol 140 mg, Goldaru Pharma Co. Isfahan-Iran) and women in the control group will receive placebo tablets (Goldaru Pharma Co. Isfahan-Iran) daily in two meals (after breakfast and dinner) for 12 weeks along with standard treatment of endometrioma (dienogest 2mg/day, NSAIDs, estrogen and progesterone). The therapeutic doses of silymarin have been considered safe and well-tolerated in humans without any interaction with endometriosis treatment
ThoseAll participants in the intervention group received Liverpoolwill receive a dose of 280 mg silymarin including two tablets of Livergol 140 mg twice daily for three months, Goldaru Pharma Co. Isfahan-Iran) and thosewomen in the control group receivedwill receive placebo for exactly three months with exactly the same appearance as the Liverpool tablettablets (Goldaru Pharma Co. Isfahan-Iran) daily in two meals (after breakfast and with the same order. All people receive this drugdinner) for 12 weeks along with their usual treatments (which include painkillers such as NSAIDs or a varietystandard treatment of hormonal compounds includingendometrioma (dienogest 2mg/day, NSAIDs, estrogen and progesterone (LD tablets)). The therapeutic doses of silymarin have been considered safe and well-tolerated in humans without any interaction with the sameendometriosis treatment protocol according to the treatment of endometrial lesions. There is no drug between conventional endometrioma treatment and Liverpool treatment.
Lesion volume; Interleukin 6 levels
the size of endometrioma lesions; Interleukin 6 levels
Lesion volumethe size of endometrioma lesions; Interleukin 6 levels
General information
To evaluate the effect of Silymarin (Livergol) on IL-6 levels and endometrioma lesions: A Randomized Double-blind Placebo-controlled Trial
To evaluate the effectiveness of Silymarin (Livergol) on IL-6 levels and size of endometrioma lesions
To evaluate the effecteffectiveness of Silymarin (Livergol) on IL-6 levels and size of endometrioma lesions: A Randomized Double-blind Placebo-controlled Trial
To evaluate the effect of Silymarin (Livergol) on IL-6 levels and endometrioma lesions: A Randomized Double-blind Placebo-controlled Trial
To evaluate the effectiveness of Silymarin (Livergol) on IL-6 levels and size of endometrioma lesions in women with ovarian endometriosis: a randomized, double-blind placebo-controlled trial
To evaluate the effecteffectiveness of Silymarin (Livergol) on IL-6 levels and size of endometrioma lesions in women with ovarian endometriosis: A Randomized Doublea randomized, double-blind Placeboplacebo-controlled Trialtrial
Iranian Married Women in Fertility range (15-49)
No chronic disease (diabetes, hypertension, liver and kidney disease, previous venous embolism ...) based on medical records
Endometrioma based on gynecologist's diagnosis according to ultrasound sonography and marker CA125
People are willing to participate in the study
Iranian married women of reproductive age (15-49)
No chronic disease (diabetes, hypertension, liver and kidney disease, previous venous embolism ...) based on medical records
Women with a confirmed diagnosis of ovarian endometriosis via transvaginal ultrasonography performed by a single sonologist and CA125 level
People are willing to participate in the study
Iranian Married Women in Fertility rangemarried women of reproductive age (15-49) No chronic disease (diabetes, hypertension, liver and kidney disease, previous venous embolism ...) based on medical records Endometrioma based on gynecologist'sWomen with a confirmed diagnosis according to ultrasound sonographyof ovarian endometriosis via transvaginal ultrasonography performed by a single sonologist and marker CA125 level People are willing to participate in the study
People with drug side effects.
Individuals unwilling to continue to participate in the study
Failure to comply with treatment protocol
participants suffering from the side effects of silymarin
Individuals unwilling to continue participating in the study
Failure to comply with treatment protocol
Taking specific medications such as anti-depressant, GnRH analogues, systemic glucocorticoids, or other milk thistle products and anti-inflammatory supplements with a specified wash-out period for each one
People with drugparticipants suffering from the side effects. of silymarin Individuals unwilling to continue to participateparticipating in the study Failure to comply with treatment protocol Taking specific medications such as anti-depressant, GnRH analogues, systemic glucocorticoids, or other milk thistle products and anti-inflammatory supplements with a specified wash-out period for each one
افرادی که دچار عوارض مصرف دارو می شوند
دم تمایل افراد به ادامه شرکت در مطالعه
عدم رعایت پروتکل درمانی
افرادی که دچار عوارض مصرف دارو می شوند
عدم تمایل افراد به ادامه شرکت در مطالعه
عدم رعایت پروتکل درمانی
مصرف داروهای خاص مانند ضد افسردگی، آنالوگ های GnRH، گلوکوکورتیکوئیدهای سیستمیک، یا سایر محصولات گیاه خار مریم و مکمل های ضد التهابی با دورهwash-out مشخص برای هر کدام
افرادی که دچار عوارض مصرف دارو می شوند دمعدم تمایل افراد به ادامه شرکت در مطالعه عدم رعایت پروتکل درمانی مصرف داروهای خاص مانند ضد افسردگی، آنالوگ های GnRH، گلوکوکورتیکوئیدهای سیستمیک، یا سایر محصولات گیاه خار مریم و مکمل های ضد التهابی با دورهwash-out مشخص برای هر کدام
This study is randomized using permuted block randomization contains 4th block (two participants in experimental group and two participants in placebo group) by the Random allocation software .
Simple randomization will be done according to a computer-generated list of random number groups prepared using Statistical Analysis System Software Version 9.2 (SAS Institute Inc., Cary, NC, USA). All participants will be randomly allocated to each arm and given the tablets based on a computer-generated randomization list by the investigator.
This study is randomizedSimple randomization will be done according to a computer-generated list of random number groups prepared using permuted blockStatistical Analysis System Software Version 9.2 (SAS Institute Inc., Cary, NC, USA). All participants will be randomly allocated to each arm and given the tablets based on a computer-generated randomization contains 4th block (two participants in experimental group and two participants in placebo group)list by the Random allocation software investigator.
دراین مطالعه از روش تصادفی سازی بلوکی شامل بلوکهای 4 تایی(2 شرکت کننده در گروه مداخله و 2 شرکت کننده در گروه کنترل)با استفاده از نرم افزار تولید توالی تصادفی استفاده شده است.
تصادفیسازی ساده بر اساس فهرستی از گروههای اعداد تصادفی تولید شده توسط رایانه که با استفاده از نرمافزار سیستم تحلیل آماری نسخه 9.2 (SAS Institute Inc., Cary, NC, USA) تهیه شده است، انجام خواهد شد. همه شرکتکنندگان بهطور تصادفی به هر بازو اختصاص داده میشوند و براساس فهرست تصادفیسازی رایانهای توسط محقق، قرصها به آنها داده میشود.
دراین مطالعهتصادفیسازی ساده بر اساس فهرستی از روشگروههای اعداد تصادفی سازی بلوکی شامل بلوکهای 4 تایی(2 شرکت کننده در گروه مداخله و 2 شرکت کننده در گروه کنترل)باتولید شده توسط رایانه که با استفاده از نرمافزار تولید توالی تصادفی استفادهسیستم تحلیل آماری نسخه 9.2 (SAS Institute Inc., Cary, NC, USA) تهیه شده است، انجام خواهد شد. همه شرکتکنندگان بهطور تصادفی به هر بازو اختصاص داده میشوند و براساس فهرست تصادفیسازی رایانهای توسط محقق، قرصها به آنها داده میشود.
The researcher and patient will be unaware of the treatment and grouping of the study. For this purpose, Levergel tablets and placebo are coded by a research center. The lead researcher treats patients in a double-blind manner based on the drug package code. The code for the drug package is recorded on the personal information form, and the researcher who completes the information form will not be informed of the type of treatment.
The researcher and patients will be unaware of the treatment and grouping of the study. For this purpose, Levergol tablets and placebo are coded by a research center. The lead researcher treats patients in a double-blind manner based on the drug package code. The code for the drug package is recorded on the personal information form, and the researcher who completes the information form will not be informed of the type of treatment.
The researcher and patientpatients will be unaware of the treatment and grouping of the study. For this purpose, LevergelLevergol tablets and placebo are coded by a research center. The lead researcher treats patients in a double-blind manner based on the drug package code. The code for the drug package is recorded on the personal information form, and the researcher who completes the information form will not be informed of the type of treatment.
Protocol summary
Study aim
Evaluation and comparison of the effectiveness of silymarin tablet (Levergol) on size of endometrioma lesions and interleukin-6 level in women with ovarian endometriosis before and after intervention
Design
they are randomly divided into two groups: A (intervention group) and B (control group).
The sample size required is pilot study of at least 10 patients in each group as a pilot study in Phase II of the clinical trial.
Settings and conduct
Gynecologists perform in hospitals and offices.
For this purpose, Levergol tablets and placebo are coded by a research center. The lead researcher treats patients in a double-blind manner based on the drug package code. The code for the drug package is recorded on the personal information form and the researcher who completes the information form will not be informed of the type of treatment.
Participants/Inclusion and exclusion criteria
Iranian married women of reproductive age (15-49); with a confirmed diagnosis of ovarian endometriosis via transvaginal ultrasonography performed by a single sonologist and CA125 level;
No chronic disease based on medical records; without taking specific medications or anti-inflammatory supplements with a specified wash-out period for each one
Intervention groups
All participants in the intervention group will receive a dose of 280 mg silymarin including two tablets of Livergol 140 mg, Goldaru Pharma Co. Isfahan-Iran) and women in the control group will receive placebo tablets (Goldaru Pharma Co. Isfahan-Iran) daily in two meals (after breakfast and dinner) for 12 weeks along with standard treatment of endometrioma (dienogest 2mg/day, NSAIDs, estrogen and progesterone). The therapeutic doses of silymarin have been considered safe and well-tolerated in humans without any interaction with endometriosis treatment
Main outcome variables
the size of endometrioma lesions; Interleukin 6 levels
General information
Reason for update
Completion of the sampling process and statistical analysis led us to update the recorded information of different sections of this trial in IRCT. As we have believed that this study might hold enormous potential for improving promising therapeutic agents to benefit patients who are suffering from various manifestations of endometriosis, especially endometrioma.
Unfortunately, while updating the information related to the actual recruitment start/end dates, we noticed an inadvertent error in recording the expected recruitment start and end dates of the sampling, and a need has been felt on the imperative for transparency, accountability in order to fix that error and explain its causes to re-establish researchers’ trust in this clinical trial’s accuracy and reliability.
All available evidence, including the date of approval of this clinical trial in the ethics committee of Tarbiat Modares University (IR.MODARES.REC.1398.143) and the date of entry of the researcher to the master's degree (1397-98 academic year) indicate an inadvertent error in the registration of this study and make the possibility of conducting this study in that time (before registration) unfeasible. We take full responsibility for the situation and all of patients’ consents and questionnaire forms with detailed for the current study are available upon any requests.
In addition, the simultaneous recruiting of patients and the coronavirus pandemic and its lockdown resulted in study participants’ inaccessibility and trial personnel for in-person scheduled study visits and/or follow-up led to prolong sampling process and its postponement.
Acronym
IRCT registration information
IRCT registration number:IRCT20150905023897N5
Registration date:2020-02-04, 1398/11/15
Registration timing:prospective
Last update:2022-02-23, 1400/12/04
Update count:2
Registration date
2020-02-04, 1398/11/15
Registrant information
Name
ِDr. Shahideh Jahanian Sadatmahalleh
Name of organization / entity
Tarbiat Modares University
Country
Iran (Islamic Republic of)
Phone
+98 21 8288 4826
Email address
shahideh.jahanian@modares.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-02-07, 1398/11/18
Expected recruitment end date
2021-03-14, 1399/12/24
Actual recruitment start date
2020-03-02, 1398/12/12
Actual recruitment end date
2021-05-18, 1400/02/28
Trial completion date
2021-08-21, 1400/05/30
Scientific title
To evaluate the effectiveness of Silymarin (Livergol) on IL-6 levels and size of endometrioma lesions in women with ovarian endometriosis: a randomized, double-blind placebo-controlled trial
Public title
To evaluate the effectiveness of Silymarin (Livergol) on IL-6 levels and size of endometrioma lesions
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Iranian married women of reproductive age (15-49)
No chronic disease (diabetes, hypertension, liver and kidney disease, previous venous embolism ...) based on medical records
Women with a confirmed diagnosis of ovarian endometriosis via transvaginal ultrasonography performed by a single sonologist and CA125 level
People are willing to participate in the study
Exclusion criteria:
participants suffering from the side effects of silymarin
Individuals unwilling to continue participating in the study
Failure to comply with treatment protocol
Taking specific medications such as anti-depressant, GnRH analogues, systemic glucocorticoids, or other milk thistle products and anti-inflammatory supplements with a specified wash-out period for each one
Age
From 15 years old to 49 years old
Gender
Female
Phase
2
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Data and Safety Monitoring Board
Sample size
Target sample size:
60
Actual sample size reached:
70
Randomization (investigator's opinion)
Randomized
Randomization description
Simple randomization will be done according to a computer-generated list of random number groups prepared using Statistical Analysis System Software Version 9.2 (SAS Institute Inc., Cary, NC, USA). All participants will be randomly allocated to each arm and given the tablets based on a computer-generated randomization list by the investigator.
Blinding (investigator's opinion)
Double blinded
Blinding description
The researcher and patients will be unaware of the treatment and grouping of the study. For this purpose, Levergol tablets and placebo are coded by a research center. The lead researcher treats patients in a double-blind manner based on the drug package code. The code for the drug package is recorded on the personal information form, and the researcher who completes the information form will not be informed of the type of treatment.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Tarbiat Modares university
Street address
Jalal AleAhmad-Nasr, Tarbiat Modares University
City
Tehran
Province
Tehran
Postal code
11114115
Approval date
2019-10-22, 1398/07/30
Ethics committee reference number
IR.MODARES.REC.1398.143
Health conditions studied
1
Description of health condition studied
Endometrioma lesions
ICD-10 code
N80.1
ICD-10 code description
Endometriosis of ovary
Primary outcomes
1
Description
Interleukin 6 levels
Timepoint
At the beginning of the study and three months after starting the Livergol pill
Method of measurement
Using the ELISA method in pg / ml
2
Description
Endometrial lesion volume measurement
Timepoint
At the beginning of the study and three months after starting the Livergol pill
Method of measurement
ultrasound or laparoscopy in millimeters
3
Description
Sexual function
Timepoint
At the beginning of the study and three months after starting the Livergol pill
Method of measurement
Using the FSFI questionnaire
4
Description
Quality of Life
Timepoint
At the beginning of the study and three months after starting the Livergol pill
Method of measurement
Using the SF-12 questionnaire
5
Description
Pelvic pain
Timepoint
At the beginning of the study and three months after starting the Livergol pill
Method of measurement
VAS visual analog scale
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: People in the intervention group receive Liverpool 140 mg tablets at the pharmaceutical company twice daily for three months.
Category
Treatment - Drugs
2
Description
Control group: People in the control group used the placebo for exactly three months with exactly the same appearance of the Levergel tablet twice a day for three months.