Ignite Creation Date:
2024-05-06 @ 6:29 PM
Last Modification Date:
2024-10-26 @ 2:49 PM
Study NCT ID:
NCT05680805
Status:
RECRUITING
Last Update Posted:
2023-08-01
First Post:
2022-10-27
Brief Title:
Metabolic Responses of Metformin and Genetic Polymorphisms of SLC22A1 Gene in PCOS
Sponsor:
Bangabandhu Sheikh Mujib Medical University Dhaka Bangladesh
Organization:
Bangabandhu Sheikh Mujib Medical University Dhaka Bangladesh
Study Overview
Official Title:
Metabolic Responses of Metformin and Genetic Polymorphisms rs628031 and rs2282143 of Solute Carrier Family 22 Member 1 Gene in Polycystic Ovary Syndrome
Status:
RECRUITING
Status Verified Date:
2024-08
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 aim of this study is to see the associations of metabolic responses of metformin with single nucleotide polymorphisms SNPs rs628031 and rs2282143 of solute carrier family 22 member 1 SLC22A1 gene in women with polycystic ovary syndrome PCOS This prospective clinical study will be conducted in the department of Endocrinology Bangabandhu Sheikh Mujib Medical University BSMMU from February 2023 to September 2024 over a period of two years A total of at least 100 women with PCOS 18 - 35 years diagnosed based on International Evidence-based Guideline for PCOS 2018 will be included consecutively by convenient sampling After taking informed written consent relevant clinical history will be taken and physical examinations will be done at baseline Following a run in phase of three weeks patients will visit thrice after 1 12 24 weeks of metformin maintenance therapy with a window period of 14 days both ways Blood samples will be collected in fasting state at baseline and after 24 weeks of treatment to measure glycemic status lipid profile fasting insulin c-peptide and detection of SLC22A1 gene rs628031 and rs2282143 polymorphisms Glucose will be measured by glucose oxidase method lipids by glycerol phosphate dehydrogenase peroxidase method insulin by chemiluminescent microparticle immunoassay c-peptide by enzyme-linked immunosorbent assay ELISA and genetic analysis of rs628031 and rs2282143 by polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP
Detailed Description:
Objectives of the Study General objective Determination of the association of metabolic responses to metformin with SLC22A1 gene polymorphisms rs628031 and rs2282143 in women with PCOS Specific objectives
To see the changes of metabolic profile body mass index waist circumference blood pressure glycemic status insulin resistance c-peptide and lipid in 24 weeks of metformin therapy in women with PCOS
Determination of frequency of SLC22A1 gene polymorphisms rs628031 and rs2282143 in women with PCOS
Categorization of PCOS patients according to SLC22A1 gene polymorphisms rs628031 and rs2282143 into wild and variant groups
Comparison of metabolic changes of 24 weeks of metformin therapy between wild vs variant group of SLC22A1 gene polymorphisms rs628031 and rs2282143 in women with PCOS
Others
Determination of the short-term side-effects of metformin in women with PCOS
Comparison of metformin side-effects in women with PCOS with or without SLC22A1 gene polymorphisms rs628031 and rs2282143
Materials and Methods
Type of study
Prospective clinical study
Place of study
Department of Endocrinology BSMMU
Study period
October 2022 to September 2024
Study population
Reproductive aged 18 - 35 years women of PCOS
Sampling method
Consecutive purposiveconvenient sampling
Sample size
The sample size will be calculated from following formula
n Zα Zβ2 σ12 σ22 μ1 - μ22 From a previous similar study the 2 hours OGTT glucoseinsulin ratio GIR before and after 24 weeks of metformin therapy were 2325 and 3232 in variant genotype and 2019 and 3929 respectively in wild genotype of SLC22A1 rs628031 The mean differences in variant and wild genotype were 0907 and 1910 respectively
Here Zα 196 at 95 confidence level Zβ 128 at 90 power μ1 mean changes of GIR after metformin in variant genotype of rs628031 AGGG 09 μ2 mean of GIR after metformin in wild genotype of rs628031AA 19 Assuming standard deviation SD 15 σ1σ2 in both groups
Minimum number of sample to be studied in each group n 196 1282 152 152 09 - 192
3242 225 225 102
1050 450 1 4725 1 4725 At least 94 patients with PCOS are required for this study However considering dropout at least 100 patients with PCOS will be taken for the study Sample size may be increased if required
Study procedure Newly diagnosed at least 100 women of reproductive age 18 - 35 years PCOS patients will be consecutively recruited from the department of Endocrinology BSMMU Informed written consent will be taken from patients and asked to come in fasting state on particular day time and place twice a week Related history reproductive personal and family history will be taken and physical examination height weight waist circumference hip circumference acne hirsutism acanthosis nigricans will be done and all data will be documented in a pretested semi-structured questionnaire
Blood sample collection at baseline
About 10 ml of venous blood will be drawn from each participant with 8 - 12 hours of fasting Then a 75 gm oral glucose tolerance test OGTT will be done and another five ml of blood will be collected after two hours About two ml of blood collected during fasting and two hours after OGTT will be kept in fluorinated tube for blood glucose measurement on the same day of collection Additional two ml of whole blood will be preserved at -70 degree Celcius in the department of Endocrinology for polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP after completing all biochemical analysis to avoid bias Remaining six ml blood collected during fasting and three ml of blood collected after OGTT will be kept standing for 15 minutes to allow clotting After centrifugation serum will be separated and kept into eppendorf After proper labeling they will be preserved in a -700C refrigerator Biochemical analysis glucose and lipid profile of the serum will be done on the same day and insulin and c-peptide within seven days of collection
Interventions Lifestyle modifications Patients will be counseled at the time of diagnosis and a written document will be provided
Diet
An individualized diet chart prepared by dietitian will be provided
Overweightobese An energy deficit of 500 Kcalday diet from weight maintenance diet
Others Weight maintenance diet Physical activity
A minimum of 150 minutesweek of moderate intensity physical activity brisk walking at a rate of 6 kmh with muscle strengthening activities on 2 non-consecutive daysweek
activity be performed in at least 10-minute bouts or around 1000 steps aiming to achieve at least 30 minutes daily at least 5 days a week
Metformin prescription Ingredients of each tablet of metformin Each tablet of metformin contains metformin 500 mg HCl BP along with inactive ingredients of povidone microcrystalline cellulose croscarmellose sodium and magnesium stearate In addition the coating for the tablets contains polyethylene glycol polyvinyl alcohol titanium dioxide talc gum acacia maltodextrin propylene glycol and natural flavors
Inventory All the tablets of metformin will be dispensed periodically to the study participants by the researcher at baseline and 1st visit after week 1 and 2nd follow up visit after 12 weeks of metformin maintenance therapy 1500 mgday Metformin tablets will be preserved as per the instructions of manufacturer Expiry date and quality of the drugs will be checked periodically
Run-in phase Metformin will be prescribed at 500 mg once daily after dinner and will increase to 1500 mgday in three divided doses after main meals within two weeks of initiation Patients will be asked to come with a chart of drug compliance and side-effects one week after initiation of 1500 mgday of metformin Patients who will not able to tolerate 1500 mgday be excluded from the study for analysis of metabolic responses
Maintenance dose 1500 mgday in three divided dose for 24 weeks Follow up Patients will be requested to come for three follow up visits after 1 12 and 24 weeks of maintenance metformin therapy with a window period of two weeks both ways During 1st follow up visit after 1 week patients drug compliance and side-effects will be monitored clinical status along with lifestyle and drugs compliance and adverse effects will be documented after 12 weeks 2nd follow up visit After 24 weeks 3rd visit patients biochemical metabolic profiles will also be done with above mentioned clinical information
Blood sample collection after 24 weeks About eight ml of venous blood after 24 weeks of metformin therapy with 8 - 12 hours of fasting will be collected to measure FBG HbA1C insulin c-peptide and lipid profile and a 75 gm OGTT followed by five ml of blood will be collected for measurement of glucose and insulin
Drug compliance
It will be monitored over phone weekly for the first two weeks and then each visit to the researcher Patients will be requested to come with empty blisters of metformin A record book will be maintained to monitor compliance properly Patients with drug compliance 95 at any time of the study will be excluded from the analysis for metabolic responses
Adverse events monitoring
On each visit patients will be provided with an adverse event AE diary for noting pre-specified gastro-intestinal GI events They will also be asked for any serious adverse effect SAE or other AE apart from GI event All AE and SAE will be recorded in given AE form and will be preserved in patients files Patients will be advised to strictly use barrier contraception Serum ALT and creatinine will be measured after 24 weeks of metformin therapy also
To see the changes of metabolic profile body mass index waist circumference blood pressure glycemic status insulin resistance c-peptide and lipid in 24 weeks of metformin therapy in women with PCOS
Determination of frequency of SLC22A1 gene polymorphisms rs628031 and rs2282143 in women with PCOS
Categorization of PCOS patients according to SLC22A1 gene polymorphisms rs628031 and rs2282143 into wild and variant groups
Comparison of metabolic changes of 24 weeks of metformin therapy between wild vs variant group of SLC22A1 gene polymorphisms rs628031 and rs2282143 in women with PCOS
Others
Determination of the short-term side-effects of metformin in women with PCOS
Comparison of metformin side-effects in women with PCOS with or without SLC22A1 gene polymorphisms rs628031 and rs2282143
Materials and Methods
Type of study
Prospective clinical study
Place of study
Department of Endocrinology BSMMU
Study period
October 2022 to September 2024
Study population
Reproductive aged 18 - 35 years women of PCOS
Sampling method
Consecutive purposiveconvenient sampling
Sample size
The sample size will be calculated from following formula
n Zα Zβ2 σ12 σ22 μ1 - μ22 From a previous similar study the 2 hours OGTT glucoseinsulin ratio GIR before and after 24 weeks of metformin therapy were 2325 and 3232 in variant genotype and 2019 and 3929 respectively in wild genotype of SLC22A1 rs628031 The mean differences in variant and wild genotype were 0907 and 1910 respectively
Here Zα 196 at 95 confidence level Zβ 128 at 90 power μ1 mean changes of GIR after metformin in variant genotype of rs628031 AGGG 09 μ2 mean of GIR after metformin in wild genotype of rs628031AA 19 Assuming standard deviation SD 15 σ1σ2 in both groups
Minimum number of sample to be studied in each group n 196 1282 152 152 09 - 192
3242 225 225 102
1050 450 1 4725 1 4725 At least 94 patients with PCOS are required for this study However considering dropout at least 100 patients with PCOS will be taken for the study Sample size may be increased if required
Study procedure Newly diagnosed at least 100 women of reproductive age 18 - 35 years PCOS patients will be consecutively recruited from the department of Endocrinology BSMMU Informed written consent will be taken from patients and asked to come in fasting state on particular day time and place twice a week Related history reproductive personal and family history will be taken and physical examination height weight waist circumference hip circumference acne hirsutism acanthosis nigricans will be done and all data will be documented in a pretested semi-structured questionnaire
Blood sample collection at baseline
About 10 ml of venous blood will be drawn from each participant with 8 - 12 hours of fasting Then a 75 gm oral glucose tolerance test OGTT will be done and another five ml of blood will be collected after two hours About two ml of blood collected during fasting and two hours after OGTT will be kept in fluorinated tube for blood glucose measurement on the same day of collection Additional two ml of whole blood will be preserved at -70 degree Celcius in the department of Endocrinology for polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP after completing all biochemical analysis to avoid bias Remaining six ml blood collected during fasting and three ml of blood collected after OGTT will be kept standing for 15 minutes to allow clotting After centrifugation serum will be separated and kept into eppendorf After proper labeling they will be preserved in a -700C refrigerator Biochemical analysis glucose and lipid profile of the serum will be done on the same day and insulin and c-peptide within seven days of collection
Interventions Lifestyle modifications Patients will be counseled at the time of diagnosis and a written document will be provided
Diet
An individualized diet chart prepared by dietitian will be provided
Overweightobese An energy deficit of 500 Kcalday diet from weight maintenance diet
Others Weight maintenance diet Physical activity
A minimum of 150 minutesweek of moderate intensity physical activity brisk walking at a rate of 6 kmh with muscle strengthening activities on 2 non-consecutive daysweek
activity be performed in at least 10-minute bouts or around 1000 steps aiming to achieve at least 30 minutes daily at least 5 days a week
Metformin prescription Ingredients of each tablet of metformin Each tablet of metformin contains metformin 500 mg HCl BP along with inactive ingredients of povidone microcrystalline cellulose croscarmellose sodium and magnesium stearate In addition the coating for the tablets contains polyethylene glycol polyvinyl alcohol titanium dioxide talc gum acacia maltodextrin propylene glycol and natural flavors
Inventory All the tablets of metformin will be dispensed periodically to the study participants by the researcher at baseline and 1st visit after week 1 and 2nd follow up visit after 12 weeks of metformin maintenance therapy 1500 mgday Metformin tablets will be preserved as per the instructions of manufacturer Expiry date and quality of the drugs will be checked periodically
Run-in phase Metformin will be prescribed at 500 mg once daily after dinner and will increase to 1500 mgday in three divided doses after main meals within two weeks of initiation Patients will be asked to come with a chart of drug compliance and side-effects one week after initiation of 1500 mgday of metformin Patients who will not able to tolerate 1500 mgday be excluded from the study for analysis of metabolic responses
Maintenance dose 1500 mgday in three divided dose for 24 weeks Follow up Patients will be requested to come for three follow up visits after 1 12 and 24 weeks of maintenance metformin therapy with a window period of two weeks both ways During 1st follow up visit after 1 week patients drug compliance and side-effects will be monitored clinical status along with lifestyle and drugs compliance and adverse effects will be documented after 12 weeks 2nd follow up visit After 24 weeks 3rd visit patients biochemical metabolic profiles will also be done with above mentioned clinical information
Blood sample collection after 24 weeks About eight ml of venous blood after 24 weeks of metformin therapy with 8 - 12 hours of fasting will be collected to measure FBG HbA1C insulin c-peptide and lipid profile and a 75 gm OGTT followed by five ml of blood will be collected for measurement of glucose and insulin
Drug compliance
It will be monitored over phone weekly for the first two weeks and then each visit to the researcher Patients will be requested to come with empty blisters of metformin A record book will be maintained to monitor compliance properly Patients with drug compliance 95 at any time of the study will be excluded from the analysis for metabolic responses
Adverse events monitoring
On each visit patients will be provided with an adverse event AE diary for noting pre-specified gastro-intestinal GI events They will also be asked for any serious adverse effect SAE or other AE apart from GI event All AE and SAE will be recorded in given AE form and will be preserved in patients files Patients will be advised to strictly use barrier contraception Serum ALT and creatinine will be measured after 24 weeks of metformin therapy also
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