Ignite Creation Date:
2024-05-06 @ 6:44 PM
Last Modification Date:
2024-10-26 @ 2:53 PM
Study NCT ID:
NCT05767515
Status:
COMPLETED
Last Update Posted:
2024-03-05
First Post:
2023-03-02
Brief Title:
The Effects of Acetyl-L-Carnitine and MyoChiro-Inositol in Patients With PCOS
Sponsor:
Khyber Medical University Peshawar
Organization:
Khyber Medical University Peshawar
Study Overview
Official Title:
The Effects of Acetyl L--Carnitine and MyoChiro-Inositol on Improving Ovulation Pregnancy Rate Ovarian Function and Perceived Stress Response in Patients With PCOS
Status:
COMPLETED
Status Verified Date:
2024-09
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:
PCOS
Brief Summary:
The large number of women in their child bearing age is affected by Polycystic ovarian syndrome PCOS leading to infertility However it is considered as a multisystem disorder with comorbidities rather than a gynecological and a dermatological problem Patient mostly have anovulation presented as oligomennorhea or amenorrhea and hyperandrogenism presented as hirsutism along with hyperinsulinemia and insulin resistance Many etiological factors are reported but those actually responsible for PCOS in females still need to be explored However hyperandrogenism and insulin resistance being the key triggering condition apart from cardiovascular disease type 2 diabetes hypertension and obesity World Health Organization WHO has considered Infertilitys as public health problem Researchers reported the obesity role in occurrence of PCOS and its Infertilitys relation
PCOS is not a simple pathophysiologic process for which one treatment address all manifestation Treatment should target specific manifestations and individualized patient goals First-line agents for ovulation induction and treatment of infertility in patients with PCOS include metformin and clomiphene alone or in combination It has been approved as category A to regulate ovulation and improves pregnancy rates in women with PCOS Mostly it result in complication like multiple follicle recruitment rate multiple pregnancy and thinning of endometrial wall leading to early abortion and endometrial cancers The use of naturally occurring compounds like myoinositol D-chiro- inositol and L- carnitine which are already part of human body are expected to produce significant results without any side effects The proposed study will provide an alternative to current treatments available for infertility due to PCOS The expected project execution time is 2 years Thus the present project will discover new insights about treatment of infertility and thus generate new knowledge which will help Academia scientists and health care professionals Results of the study will be disseminated on different forums including to policy makers Pharmaceutical national and international agencies The result will be published in journal both national and international with good impact factors The outcome of the project will be used as publication in high impact international journals filling of patents and will also be presented in national and international forums
PCOS is not a simple pathophysiologic process for which one treatment address all manifestation Treatment should target specific manifestations and individualized patient goals First-line agents for ovulation induction and treatment of infertility in patients with PCOS include metformin and clomiphene alone or in combination It has been approved as category A to regulate ovulation and improves pregnancy rates in women with PCOS Mostly it result in complication like multiple follicle recruitment rate multiple pregnancy and thinning of endometrial wall leading to early abortion and endometrial cancers The use of naturally occurring compounds like myoinositol D-chiro- inositol and L- carnitine which are already part of human body are expected to produce significant results without any side effects The proposed study will provide an alternative to current treatments available for infertility due to PCOS The expected project execution time is 2 years Thus the present project will discover new insights about treatment of infertility and thus generate new knowledge which will help Academia scientists and health care professionals Results of the study will be disseminated on different forums including to policy makers Pharmaceutical national and international agencies The result will be published in journal both national and international with good impact factors The outcome of the project will be used as publication in high impact international journals filling of patents and will also be presented in national and international forums
Detailed Description:
Introduction A tremendously high number of women in their child bearing age is affected by Polycystic ovarian syndrome PCOS leading to infertility 1 PCOS is not a simple gynecological or dermatological problem but a multisystem disorder with comorbidities Patients mostly have anovulation presented as oligomennorhea or amenorrhea and hyperandrogenism presented with symptoms of hirsutism along with hyperinsulinemia and insulin resistance The presence of multiple cysts in the ovaries however is not essential for diagnosis 2 Hyperandrogenism and insulin resistance being the key triggering condition apart from cardiovascular disease type 2 diabetes hypertension and obesity PCOS and infertility involves genetic and environmental factors however in Pakistani the cultural background of intermarriages is contributing noticeably towards the multiplicity of disease 3 World Health Organization WHO has considered infertility as public health problem It was the objective of UN conference 2015 to provide access and quality reproductive health services to all individuals Management of PCOS require prolong use of pharmaceuticals which has serious effects sometimes even fatal therefore the natural easily available cost effective nutraceuticals has tremendous effects and have now used safely in many clinical trials4 The current study aims to provide evidence to support the use of neutraceuticals in the management of PCOS in infertile patients and their comparison with standard drug used in treatment of infertility caused by PCOS This study can help run a long way in achieving the millennium goals MDG3 SGD3 to which Pakistan is a signatory and to reduce maternal mortality and improve reproductive health of its female population The following agent is used as standard drug in an infertile women with PCOS in a clinical set-up Metformin a biguanide used as first line drug for the treatment of diabetes and PCOS It works by preventing hepatic gluconeogenesis and intestinal glucose absorption thus improving insulin sensitivity 5 In addition to its systemic effects on insulin signaling it effect autocrineparacrine signaling in ovarian tissue thus improving ovarian steriodogensis and endometrial receptivity 6 In a recent study its role in infertile PCOS women was established resulting in significant number of ovulation and live birth than controls 7
Complementary and alternative medicine approach for the treatment of PCOS is becoming popular in recent years It is claimed that dietary supplements and herbal remedies are safer than conventional drugs
Acetyl L-Carnitine Carnitine a quaternary ammonium compound made in the body from lysine and methionine and is available in an active L and an inactive D form L-carnitine is available in supplemental form and has significant role in enhancing metabolism producing energy and protecting against oxidative stress Role of carnitine in treating insulin resistance is being frequently discussed with reference to accrual of acyl-CoA derivatives 8 Hence as suggested if the normal levels of carnitine in the diabetics and obese patients is ensured the insulin insensitivity can be drastically improved Further the level of L-carnitine in PCOS patients was found to be considerably less Follicogensis is a highly energy dependent process on mitochondria In PCOS the functioning of mitochondria is effected due to inflammation and other deregulations because of accumulation of testosterone and insulin in ovary It help in transport of lipids from cytosol to mitochondria in breakdown of lipids for production of energy 9 Inositol Inositols present in plants and animal a member of sugar alcohol comprising nine cyclohexane-1 2 3 4 5 6-hexol stereoisomers Being vitamin like it is made in human body as well as synthetically It is a component of cell membrane and acts as a second messenger has important role in release of different autacoids hormones and neurotransmitters 10The promising role of two of its isomers namely Myo-inositol MI and D-chiro-inositol DCI in the treatment of PCOS has been documented Studies have demonstrated that performance of MI to induce ovulation in patients with infertility due to PCOS can be improved if DCI is combined to it Best results are achieved when the two isomers are used in 401 ratio which is the normal amount in which they exist in the body 11 Both MI and DCI can influence oxidative and non-oxidative metabolism Apart from being involved in activation of multiple enzymes MI is involved in glucose transport and DCI in insulin production from B- cells and ATP production 12 DCI contributes in mediating insulin activity mainly on non-ovarian tissues MI displays specific effects on ovary chiefly by modulating glucose metabolism and FSH-signaling Moreover MI may also improve ovarian functions by modulating steroid metabolism through non-insulin-dependent pathways In PCOS patient due IR there is dysregulation in MIDCI ratio in non- ovarian tissue related to reduced epimarse activity However ovaries being insulin sensitive have lower level of MI than DCI due to increase epimerase activity 13
Rationale The incidence of PCOS is increasing throughout the world It is much higher in Pakistani women 52 than Caucasian women 20-25 and is contributing towards both primary 50 and secondary 25 infertility 14 Infertilty has its sociocultural connotations resulting in emotional and mental stress Infertilty due to PCOS should be treated with nutraceuticals for being natural cost effective easily available and with minimum side effects The inositol isomers in its physiological ratio 401 and carnitine as an antioxidant has shown significant effects in regularization of metabolic and endocrine parameters of the body Rationale of the present study is that Inositol and Carnitine alone and in combination may be a better alternate for treatment of infertility in patients with PCOS compared to Metformin To the best of our knowledge no study till date is documented for synergistic effects of Acetyl-L Carnitine and inositol isomers when used in physiological balanced ratio for infertilty Objectives 1 To compare the effects of Inositol isomers and Acetyl-LCarnitine alone and in combination with Metformin on improving ovulation pregnancy rate restoring ovarian function metabolic balance and perceived stress response in patient with PCOS Hypothesis It is hypothesized that Inositol and Acetyl L-Carnitine alone may produce better or at least comparable results to Metformin in improving Pregnancy rate ovulation restoring ovarian function metabolic balance and perceived stress response in infertile patients with PCOS
It is also hypothesized that the synergistic action of Inositol isomers and Acetyl L-Carnitine in combination may produce better or at least comparable results to Metformin in improving pregnancy rate ovulation restoring ovarian function metabolic balance and perceived stress response in infertile patients with PCOS STUDY DESIGN This will be a noncommercial randomized double blind clinical trial RCT in which subject and treatment provider will blinded to treatment intervention In this study we will compare the treatment of naturally occurring nutraceuticals with Metformin control group which is used as first line drug in treatment of PCOS for infertile women The nature of study will be explained in both Pashto and Urdu and informed consent will be taken SETTINHS OPD patients in Gynecology and Obstetrics Department Pakistan Institute of Medical Sciences Islamabad PIMS and Bacha Khan Medical Complex Swabi BKMC KP DURATION The study is expected to be completed in 1year with duration for 6 months
SAMPLE SIZE The study will include 120 patients with PCOS according to our inclusion of the NIH 2012 extension of ESHREASRM 2003 criteria
Complementary and alternative medicine approach for the treatment of PCOS is becoming popular in recent years It is claimed that dietary supplements and herbal remedies are safer than conventional drugs
Acetyl L-Carnitine Carnitine a quaternary ammonium compound made in the body from lysine and methionine and is available in an active L and an inactive D form L-carnitine is available in supplemental form and has significant role in enhancing metabolism producing energy and protecting against oxidative stress Role of carnitine in treating insulin resistance is being frequently discussed with reference to accrual of acyl-CoA derivatives 8 Hence as suggested if the normal levels of carnitine in the diabetics and obese patients is ensured the insulin insensitivity can be drastically improved Further the level of L-carnitine in PCOS patients was found to be considerably less Follicogensis is a highly energy dependent process on mitochondria In PCOS the functioning of mitochondria is effected due to inflammation and other deregulations because of accumulation of testosterone and insulin in ovary It help in transport of lipids from cytosol to mitochondria in breakdown of lipids for production of energy 9 Inositol Inositols present in plants and animal a member of sugar alcohol comprising nine cyclohexane-1 2 3 4 5 6-hexol stereoisomers Being vitamin like it is made in human body as well as synthetically It is a component of cell membrane and acts as a second messenger has important role in release of different autacoids hormones and neurotransmitters 10The promising role of two of its isomers namely Myo-inositol MI and D-chiro-inositol DCI in the treatment of PCOS has been documented Studies have demonstrated that performance of MI to induce ovulation in patients with infertility due to PCOS can be improved if DCI is combined to it Best results are achieved when the two isomers are used in 401 ratio which is the normal amount in which they exist in the body 11 Both MI and DCI can influence oxidative and non-oxidative metabolism Apart from being involved in activation of multiple enzymes MI is involved in glucose transport and DCI in insulin production from B- cells and ATP production 12 DCI contributes in mediating insulin activity mainly on non-ovarian tissues MI displays specific effects on ovary chiefly by modulating glucose metabolism and FSH-signaling Moreover MI may also improve ovarian functions by modulating steroid metabolism through non-insulin-dependent pathways In PCOS patient due IR there is dysregulation in MIDCI ratio in non- ovarian tissue related to reduced epimarse activity However ovaries being insulin sensitive have lower level of MI than DCI due to increase epimerase activity 13
Rationale The incidence of PCOS is increasing throughout the world It is much higher in Pakistani women 52 than Caucasian women 20-25 and is contributing towards both primary 50 and secondary 25 infertility 14 Infertilty has its sociocultural connotations resulting in emotional and mental stress Infertilty due to PCOS should be treated with nutraceuticals for being natural cost effective easily available and with minimum side effects The inositol isomers in its physiological ratio 401 and carnitine as an antioxidant has shown significant effects in regularization of metabolic and endocrine parameters of the body Rationale of the present study is that Inositol and Carnitine alone and in combination may be a better alternate for treatment of infertility in patients with PCOS compared to Metformin To the best of our knowledge no study till date is documented for synergistic effects of Acetyl-L Carnitine and inositol isomers when used in physiological balanced ratio for infertilty Objectives 1 To compare the effects of Inositol isomers and Acetyl-LCarnitine alone and in combination with Metformin on improving ovulation pregnancy rate restoring ovarian function metabolic balance and perceived stress response in patient with PCOS Hypothesis It is hypothesized that Inositol and Acetyl L-Carnitine alone may produce better or at least comparable results to Metformin in improving Pregnancy rate ovulation restoring ovarian function metabolic balance and perceived stress response in infertile patients with PCOS
It is also hypothesized that the synergistic action of Inositol isomers and Acetyl L-Carnitine in combination may produce better or at least comparable results to Metformin in improving pregnancy rate ovulation restoring ovarian function metabolic balance and perceived stress response in infertile patients with PCOS STUDY DESIGN This will be a noncommercial randomized double blind clinical trial RCT in which subject and treatment provider will blinded to treatment intervention In this study we will compare the treatment of naturally occurring nutraceuticals with Metformin control group which is used as first line drug in treatment of PCOS for infertile women The nature of study will be explained in both Pashto and Urdu and informed consent will be taken SETTINHS OPD patients in Gynecology and Obstetrics Department Pakistan Institute of Medical Sciences Islamabad PIMS and Bacha Khan Medical Complex Swabi BKMC KP DURATION The study is expected to be completed in 1year with duration for 6 months
SAMPLE SIZE The study will include 120 patients with PCOS according to our inclusion of the NIH 2012 extension of ESHREASRM 2003 criteria
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| FNoSG-21-153RDC691 | OTHER_GRANT | None | None |
| Pharmaevo Pakistan | OTHER | Pharmaevo Pharmaceuticals Pakistan limited | None |