Ignite Creation Date:
2024-05-06 @ 10:37 AM
Last Modification Date:
2024-10-26 @ 12:33 PM
Study NCT ID:
NCT03306745
Status:
COMPLETED
Last Update Posted:
2018-09-06
First Post:
2017-07-16
Brief Title:
Micronutrient Supplementation in PCO-syndrome
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
Official Title:
Micronutrient Supplementation for Women With PCO-syndrome - Influence of Nutrition and Physiology on the Development of PCOS-typical Parameters
Status:
COMPLETED
Status Verified Date:
2018-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The role of micronutrients in fertility has recently gained increased attention In women who suffer from polycystic ovary syndrome PCOS and infertility we aim to test the impact of a standardized multinutrient supplementation on the course of PCOS-specific parameters namely anti-Mullerian hormone AMH testosterone and androstenedione A total of 60 infertile women with PCOS previously untreated will be randomized to receive either a combined standardized multinutrient supplementation containing folic acid selenium vitamin E catechins glycyrrhizin coenzyme Q10 and omega-3-fatty acids study group or folic acid alone control group in a double-blinded randomized manner These study medications will be provided for 3 months and pre- to posttreatment levels of AMH testosterone and AMH will be analysed The study will be performed at the Clinical Division of Gynecologic Endocrinology and Reproductive Medicine of the Medical University of Vienna
Detailed Description:
Introduction and scientific background
In the Western world malnutrition and subfertility have become increasingly common problems affecting both men and women A recent study showed that conforming to nutritional recommendations significantly increased the probability of a clinical pregnancy following vitro fertilisation IVF intracytoplasmatic sperm injection ICSI They included fruit vegetables certain types of meat fish whole-grain products and specific fats according to the Netherlands Nutrition Centre Foundation Another study specifically analysed preconceptional consumption of unsaturated fatty acids by women before IVFICSI It discovered a positive effect on the embryos morphology
The effect of micronutrients on female fertility is currently under investigation A 2012 review on the subject included 13 studies with more than 90000 female participants and provided no generalised recommendations but allowed the authors to deduce a certain positive effect of supplementation with certain micronutrients on female fertility
This current study will test the effect of a currently available micronutrient supplementation in women suffering from polycystic ovary PCO-syndrome and sterility The product PROfertil female Lenus Pharma Seeböckgasse 59 1160 Vienna Austria is based on several studies that showed i an increased need for these micronutrients of women with a desire to have a child or currently pregnant andor ii a positive effect on female fertility PROfertil female is a micronutrient supplement containing selenium vitamin E catechins glycyrrhizin co-enzyme Q10 folic acid and omega-3 fatty acids
This study seems of impact from a scientific perspective Clinical experience with PROfertil female suggests that patients suffering from PCO-syndrome experience an increase of anti-müllerian hormone and androgen levels The reductive effect of PCO-typical serum parameters can be explained pathophysiologically A chronic low-level pro-inflammatory state - both locally in the ovary and systemically - appears to be among the central pathophysiological correlates of PCO-syndrome PROfertil female contains a mix of several antioxidative agents A favourable effect on PCO-syndrome is expected Metformin is an anti-inflammatory substance commonly used to treat PCO-syndrome The anti-inflammatory effect is seen as positive This explains why women suffering from PCO-syndrome without insulin-glucose balance problems react positively to treatment with metformin
The aim of this study is to perform a prospective randomized test comparing PROfertil female to supplementation with folic acid alone for female patients suffering from PCO-syndrome and infertility Supplementation with folic acid is the current state of the art in micronutrient supplementation of infertile women
Study aims The primary aim of this study is to analyse the effects of three months of treatment with PROfertil female compared to a supplementation with 400µg of folic acid for women suffering from PCO-syndrome sterility anovulation The study will examine the parameters typical for PCO-syndrome anti-müllerian hormone total testosterone androstenedione
The secondary goal is to document the individual course of further fertility treatment
The products being administered to the patients for four weeks are
PROfertil female Lenus Pharma Gesellschaft mit beschränkter Haftung GesmbH Seeböckgasse 59 1160 Vienna treatment group - one soft capsule 500mg Omega-3-fatty acids and one pill folic acid 800µg selenium 70µg vitamin E 30mg catechine 4mg glycyrrhizin 12mg and coenzyme Q10 30mg per day
200µg folic acid folic acid capsules 400µg OTC Produktion und Forschung GesmbH Fischergasse 17 5020 Salzburg control group - two capsules per day
The study will be performed in a double-blinded manner The medications are unlabeled for both groups and will be dispensed in unlabeled blisters However patients could search for the actual look of the PROfertil female soft capsules and the pills for example on the internet Since they differ from the folic acid capsules patients could identify the control medications The study team is aware of the fact that this kind of blinding is not according to standards and could introduce some kind of bias
Study hypotheses
First hypothesis A three-month treatment with PROfertil female causes a drop of anti-müllerian hormone total testosterone and androstenedione levels This does not happen if treated with 400µg folic acid
Outcome parameters
Primary outcome parameters anti-müllerian hormone AMH total testosterone and androstenedione levels
Study design
Monocentric prospective randomized double-blinded trial
Recruitment
The participants are recruited by medical professionals at the Department of Obstetrics and Gynecology of the Medical University of Vienna using the above mentioned criteria during routine examinations before any treatment for PCO-syndrome andor sterility is initiated Potential participants are informed about the procedure clinical relevance and possible additional effort caused by study participation The patients willing to participate then have to sign the written informed consent
Sample size calculation
Assuming a reduction of the mean AMH levels by 2 ngml at a standard deviation of 3 ngml and an alpha value of 005 and a power of 090 the paired t-test requires 26 patients per group Due to the fact that the participants wish to conceive a child and have been diagnosed with sterility a low drop-out rate can be expected There is no reliable data on this or similar treatments that allow prediction of the chance to conceive Due to the favourable benefit-to-risk profile a 15 drop-out rate is assumed This corresponds to 4 patients per group Thus the final sample size is calculated as 30 patients per group which leads to a total study population of 60
Statistical analysis
The bio-statistician will randomise the data using nQuery advisorTM Version 70 The information will then be packaged in an envelope by a person independent of the participating medical professionals and other scientific personnel This will only be opened after the inclusion of the patient Categorical variables will be presented as absolute numbers and percentages numerical variables as median and interquartile range
The following statistical analyses are planned The result parameters and the patient characteristics of the two groups will be compared using the Welch test for numerical variables and the Chi-square-test or Fishers exact test for categorical variables A p-value of 005 is considered to be statistically significant The statistical analyses will be performed using SPSS 240 for Windows SPSS Inc 1989-2017
Further details on study design
After recruiting the participants at the outpatient clinics for Gynecologic Endocrinology and Infertility Treatment they are randomly assigned to one of the groups
Participants will receive either 2 unlabelled soft capsules containing 200µg folic acid each or 1 unlabelled soft capsule containing omega-3 fatty acids and 1 tablet containing folic acid selenium vitamin E catechins glycyrrhizin and co-enzyme Q10 see Table above for details on doses
The planned examination of AMH total testosterone and androstenedione levels will take place after a minimum of 90 days and a maximum of 100 days after beginning supplementation with PROfertil female or folic acid The maximum duration of participation is thus 100 days After taking the micronutrient supplementation PROfertil female or folic acid beyond the planned minimum treatment duration an individualised fertility treatment can be performed
There are two study-specific consultations After including the patient consultation 1 randomisation distribution of drugs and start of study and after 90 to 100 days consultation 2 During consultation 2 unused study blisters are collected and patients are questioned on peculiarities and possible side effects of the micronutrient supplementation used
It is expected that 30 minutes for consultation 1 and 15 minutes for consultation 2 will have to be spent by the patient The consultations will be held during regular outpatient treatments and will be part of the planned routine examinations They include discussions of examination results and recommendations for further treatment
Benefits-to-risk assessment and preventive measures
Risks or complications due to the use of PROfertil female and additional venepuncture are not expected A recent study using the same product showed no substance-related side effects number of the ethics committee of the Medical University of 16592013 accepted on 2013-09-24 9 A direct benefit for the treatment group is possible A positive effect on PCO syndrome can be assumed which might result in a higher chance of pregnancy The substance administered to the control group is state of the art for female fertility treatment
In the Western world malnutrition and subfertility have become increasingly common problems affecting both men and women A recent study showed that conforming to nutritional recommendations significantly increased the probability of a clinical pregnancy following vitro fertilisation IVF intracytoplasmatic sperm injection ICSI They included fruit vegetables certain types of meat fish whole-grain products and specific fats according to the Netherlands Nutrition Centre Foundation Another study specifically analysed preconceptional consumption of unsaturated fatty acids by women before IVFICSI It discovered a positive effect on the embryos morphology
The effect of micronutrients on female fertility is currently under investigation A 2012 review on the subject included 13 studies with more than 90000 female participants and provided no generalised recommendations but allowed the authors to deduce a certain positive effect of supplementation with certain micronutrients on female fertility
This current study will test the effect of a currently available micronutrient supplementation in women suffering from polycystic ovary PCO-syndrome and sterility The product PROfertil female Lenus Pharma Seeböckgasse 59 1160 Vienna Austria is based on several studies that showed i an increased need for these micronutrients of women with a desire to have a child or currently pregnant andor ii a positive effect on female fertility PROfertil female is a micronutrient supplement containing selenium vitamin E catechins glycyrrhizin co-enzyme Q10 folic acid and omega-3 fatty acids
This study seems of impact from a scientific perspective Clinical experience with PROfertil female suggests that patients suffering from PCO-syndrome experience an increase of anti-müllerian hormone and androgen levels The reductive effect of PCO-typical serum parameters can be explained pathophysiologically A chronic low-level pro-inflammatory state - both locally in the ovary and systemically - appears to be among the central pathophysiological correlates of PCO-syndrome PROfertil female contains a mix of several antioxidative agents A favourable effect on PCO-syndrome is expected Metformin is an anti-inflammatory substance commonly used to treat PCO-syndrome The anti-inflammatory effect is seen as positive This explains why women suffering from PCO-syndrome without insulin-glucose balance problems react positively to treatment with metformin
The aim of this study is to perform a prospective randomized test comparing PROfertil female to supplementation with folic acid alone for female patients suffering from PCO-syndrome and infertility Supplementation with folic acid is the current state of the art in micronutrient supplementation of infertile women
Study aims The primary aim of this study is to analyse the effects of three months of treatment with PROfertil female compared to a supplementation with 400µg of folic acid for women suffering from PCO-syndrome sterility anovulation The study will examine the parameters typical for PCO-syndrome anti-müllerian hormone total testosterone androstenedione
The secondary goal is to document the individual course of further fertility treatment
The products being administered to the patients for four weeks are
PROfertil female Lenus Pharma Gesellschaft mit beschränkter Haftung GesmbH Seeböckgasse 59 1160 Vienna treatment group - one soft capsule 500mg Omega-3-fatty acids and one pill folic acid 800µg selenium 70µg vitamin E 30mg catechine 4mg glycyrrhizin 12mg and coenzyme Q10 30mg per day
200µg folic acid folic acid capsules 400µg OTC Produktion und Forschung GesmbH Fischergasse 17 5020 Salzburg control group - two capsules per day
The study will be performed in a double-blinded manner The medications are unlabeled for both groups and will be dispensed in unlabeled blisters However patients could search for the actual look of the PROfertil female soft capsules and the pills for example on the internet Since they differ from the folic acid capsules patients could identify the control medications The study team is aware of the fact that this kind of blinding is not according to standards and could introduce some kind of bias
Study hypotheses
First hypothesis A three-month treatment with PROfertil female causes a drop of anti-müllerian hormone total testosterone and androstenedione levels This does not happen if treated with 400µg folic acid
Outcome parameters
Primary outcome parameters anti-müllerian hormone AMH total testosterone and androstenedione levels
Study design
Monocentric prospective randomized double-blinded trial
Recruitment
The participants are recruited by medical professionals at the Department of Obstetrics and Gynecology of the Medical University of Vienna using the above mentioned criteria during routine examinations before any treatment for PCO-syndrome andor sterility is initiated Potential participants are informed about the procedure clinical relevance and possible additional effort caused by study participation The patients willing to participate then have to sign the written informed consent
Sample size calculation
Assuming a reduction of the mean AMH levels by 2 ngml at a standard deviation of 3 ngml and an alpha value of 005 and a power of 090 the paired t-test requires 26 patients per group Due to the fact that the participants wish to conceive a child and have been diagnosed with sterility a low drop-out rate can be expected There is no reliable data on this or similar treatments that allow prediction of the chance to conceive Due to the favourable benefit-to-risk profile a 15 drop-out rate is assumed This corresponds to 4 patients per group Thus the final sample size is calculated as 30 patients per group which leads to a total study population of 60
Statistical analysis
The bio-statistician will randomise the data using nQuery advisorTM Version 70 The information will then be packaged in an envelope by a person independent of the participating medical professionals and other scientific personnel This will only be opened after the inclusion of the patient Categorical variables will be presented as absolute numbers and percentages numerical variables as median and interquartile range
The following statistical analyses are planned The result parameters and the patient characteristics of the two groups will be compared using the Welch test for numerical variables and the Chi-square-test or Fishers exact test for categorical variables A p-value of 005 is considered to be statistically significant The statistical analyses will be performed using SPSS 240 for Windows SPSS Inc 1989-2017
Further details on study design
After recruiting the participants at the outpatient clinics for Gynecologic Endocrinology and Infertility Treatment they are randomly assigned to one of the groups
Participants will receive either 2 unlabelled soft capsules containing 200µg folic acid each or 1 unlabelled soft capsule containing omega-3 fatty acids and 1 tablet containing folic acid selenium vitamin E catechins glycyrrhizin and co-enzyme Q10 see Table above for details on doses
The planned examination of AMH total testosterone and androstenedione levels will take place after a minimum of 90 days and a maximum of 100 days after beginning supplementation with PROfertil female or folic acid The maximum duration of participation is thus 100 days After taking the micronutrient supplementation PROfertil female or folic acid beyond the planned minimum treatment duration an individualised fertility treatment can be performed
There are two study-specific consultations After including the patient consultation 1 randomisation distribution of drugs and start of study and after 90 to 100 days consultation 2 During consultation 2 unused study blisters are collected and patients are questioned on peculiarities and possible side effects of the micronutrient supplementation used
It is expected that 30 minutes for consultation 1 and 15 minutes for consultation 2 will have to be spent by the patient The consultations will be held during regular outpatient treatments and will be part of the planned routine examinations They include discussions of examination results and recommendations for further treatment
Benefits-to-risk assessment and preventive measures
Risks or complications due to the use of PROfertil female and additional venepuncture are not expected A recent study using the same product showed no substance-related side effects number of the ethics committee of the Medical University of 16592013 accepted on 2013-09-24 9 A direct benefit for the treatment group is possible A positive effect on PCO syndrome can be assumed which might result in a higher chance of pregnancy The substance administered to the control group is state of the art for female fertility treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None