Ignite Creation Date:
2024-05-06 @ 3:21 AM
Last Modification Date:
2024-10-26 @ 11:32 AM
Study NCT ID:
NCT02274948
Status:
COMPLETED
Last Update Posted:
2017-01-02
First Post:
2014-10-19
Brief Title:
Use of Metformin in Treatment of Childhood Obesity
Sponsor:
University of Colombo
Organization:
University of Colombo
Study Overview
Official Title:
Effects of Metformin on Body Weight Composition and Metabolic Derangements in Obese Children A Randomized Clinical Trial
Status:
COMPLETED
Status Verified Date:
2016-11
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:
This study expects to evaluate the use of metformin in the management of obese children Insulin resistance among obese Sri Lankan children south Asian origin is high which had been shown in the investigators previous work
This study will look at the effect of metformin on changes in insulin resistance fatty liver state body fat content BMI and other metabolic derangement
This study will look at the effect of metformin on changes in insulin resistance fatty liver state body fat content BMI and other metabolic derangement
Detailed Description:
1 General objective To study the prevalence of Non Communicable Disease NCD related metabolic derangements among obese children and assess the outcome of two different management metformin vs placebo alongside dietary and physical activity changes modalities among 8 to16 year old obese children living in Negombo educational division of Negambo educational zone of Gampaha district in Sri Lanka
11 Specific objectives
1 To study the prevalence of obesity related metabolic derangements among obese children
2 To compare the effectiveness of the use of metformin vs placebo in the change of fat content and BMI among obese children
3 To compare the effectiveness in the use of metformin vs placebo in the reversal of insulin resistance and metabolic derangements among obese children
2 Methods 21 Study design A double blind randomized prospective placebo control study
22 Subjects and Study setting Obese more than 2 Standard Deviation SD of BMI to age on World Health Organization WHO standards school children from Negombo educational zone of district of Gampaha
Obese children had been identified in a separate screening programme it will be carried out during Sep-Dec 2013 and Sri Lanka College of Paediatricians ethical review committee has approved the study protocol carried out in this same educational division and are invited to participate in this study Children not of Sri Lankan origin or who are not planning to live in Sri Lanka during the next one year or has a secondary underlying cause for the overweightobesity will be excluded
Parents will be informed about the importance of participating in the study from the point of receiving treatment as well as participating in the research written information sheet will given and informed written consent from parentsguardians and assent from child will be obtained Any parent child who wishes not to participate will allowed doing so
23 Sample size and sampling method All children who were detected to be obese in a previous screening programme will be invited and a minimum sample size of 120 children will be recruited
The sample size is calculated that among obese children a total sample size of 60 participants would detect a between-group difference of 009 BMI SD score units approximately equivalent to a 2 kgm2 difference with 80 power Participant accrual was set at 120 participants to allow as much as 50 percent loss to follow-up However the investigators will take maximum effort to trace the patients
24 Measurements These children will be invited to participate in a follow up programme as part of clinical service as well as research Their parents will be informed to bring their children to the Loins Club of Negambo Host Diabetes Screening and Vocational Training Centre Negambo by appointment
Measurements will be done at the Loins Club of Negambo Host Diabetes Screening and Vocational Training Centre Negamboafter an overnight fast Height weight waist circumference and hip circumference will be measured Percentage fat mass will be measured using Bio Electrical Impedance BIA assay using platform type InBody 230 instrument InBody Biospace South Korea Once the impedance value is measured total body water will be calculated using the locally validated BIA prediction equation Wickramasinghe et al 2008 From Total Body Water TBW Fat Free Mass FFM and hence Fat Mass FM was calculated using age and gender specific water content of FFM Lohman 1989 Blood pressure will be measured using a mercury sphygmomanometer in seated position after 10-15 minute rest Male and female children will be assessed by trained male and female investigators respectively
Metabolic derangements will be assessed by means of total cholesterol LDL-C levels HDL-C levels triglyceride insulin Alanine amino transferase ALT and Aspartate amino transferase AST 8ml of blood into a plain bottle fasting blood sugar 2ml of blood into a NaF containing bottle Oral Glucose Toerance Test OGTT test will be done after giving anhydrous glucose 175g 192g of monohydrous glucose to max of 75g max 825g of monohydrous glucose and blood will be taken 2 hour later for random blood sugar 2ml of blood into a NaF containing bottle and serum insulin 2ml of blood into a plain bottle Serum will be separated immediately and stored at -20 degree of Celcius and analysis will be done at Loins Club of Negambo Host Diabetes Screening and Vocational Training Centre Negambo in batches Blood will be drawn after applying lignocaine Emla anesthetic cream
Insulin resistance will be calculated using Homeostatic model Insulin Resistance HOMA-IR fasting blood sugar fasting insulin 225 Matthews et al 1985 An Ultra sound scan of abdomen will be done to identify hepatic steatosis by a consultant radiologist
Pubertal staging will be assessed using visual charts Morris and Udry 1980 Girls will be shown a diagram depicting different stages of growth of breasts and pubic hair and ask them to match it with their own whenever necessary will seek mothers assistance Similarly boys are shown diagrams of external genitalia and pubic hair and to match with their own The size of the testis will be measure by the examiner using Prader orchidometer If both subject and parents were not sure of the staging with consent the examiner would examine and the correct pubertal stage assessment would be made Measurements and examinations in girls and boys will be carried out by female and male investigators respectively
The whole project will be closely supervised by a two Consultant paediatricians and after the completion of study children who need follow up will be provided the services or if they wish to be followed up at a different institute would be referred with a complete report
25 Randomization Once obesity and overweight is diagnosed and investigated they will be randomly assigned to either of one management protocol on a 11 basis Children will be categorized according to gender and age groups 8-1099 11-1399 14-16 years Using a grid for each age of each sex sequentially they will be allocated to receive management protocol I or II Only the field investigators will have information to the allocation That is Group I Structured diet Physical activity Metformin Group II Structured diet Physical activity Placebo
Dietary advice will be given by a trained nutritionist It will be based on food based dietary guidelines produced by Ministry of Health Jayatissa and Wickramasinghe 2011 Age based portion size guide will be given to parents and children and guide them on the volume they should be eating
Physical activity training will be conducted by a qualified physical activity instructor A daily physical activity routine of 20-30 minutes will be given to each student The programme would be of 3 different types based on their age 11-13 and 14-16 The workout programme will be changed every month in order to break the monotony There will 4 such different workout schedules
Medication 8-1099 year old children will receive metformin Initially children will be given 250mg of metformin daily for a week and increased to 250mg twice daily for a week and then to 500 mg twice daily there after 11-16 year old children will receive 500mg of metformin daily initially for one week which will be increased to 500mg twice daily for a week and then to 1g twice daily Children will be asked to take medication with their morning and evening meals to reduce gastro intestinal side effects and risk of hypoglycaemia Response to medication will be evaluated before each dose revision and will monitor for all possible adverse events
The study will be monitored by a Data and Safety Monitoring Committee comprising of a Paediatrician Paediatric Endocrinologist and a Bio- Statistician
Both the nutritionist and physical trainer will be blinded to the medication children will be receiving
A control group with no treatment will not be employed as it will be unethical not to do any intervention when the diagnosis of obesity is made A placebo is given to overcome any psychological effects of giving medication metformin and Placebo will be manufactured by the State Pharmaceutical Manufacturing Company SPMC The placebo tablet will be similar to metformin in all aspects except for containing the active pharmacological compound
These children will be reviewed two weeks after commencement of therapy and dose will be revised and thereafter monthly in order to ensure compliance and identify any adverse events and address issues In additionally they will be contacted via telephone weekly during first month and fortnightly afterwards to address concernsissues and also to motivate them to keep compliance at a higher level At each of these visits the anthropometry and body composition will be assessed while blood investigations will be repeated at 6 and 12 months At each eveluations one to one meeting will be held
26 Statistics The distribution of metabolic derangements will be described using descriptive statistics Spearman Correlation Coefficients will be used to assess the relationship between percentage fat and metabolic derangements related to NCD as well as anthropometric measurements and metabolic derangements Comparisons of mean values of these measurements will be made using t tests
11 Specific objectives
1 To study the prevalence of obesity related metabolic derangements among obese children
2 To compare the effectiveness of the use of metformin vs placebo in the change of fat content and BMI among obese children
3 To compare the effectiveness in the use of metformin vs placebo in the reversal of insulin resistance and metabolic derangements among obese children
2 Methods 21 Study design A double blind randomized prospective placebo control study
22 Subjects and Study setting Obese more than 2 Standard Deviation SD of BMI to age on World Health Organization WHO standards school children from Negombo educational zone of district of Gampaha
Obese children had been identified in a separate screening programme it will be carried out during Sep-Dec 2013 and Sri Lanka College of Paediatricians ethical review committee has approved the study protocol carried out in this same educational division and are invited to participate in this study Children not of Sri Lankan origin or who are not planning to live in Sri Lanka during the next one year or has a secondary underlying cause for the overweightobesity will be excluded
Parents will be informed about the importance of participating in the study from the point of receiving treatment as well as participating in the research written information sheet will given and informed written consent from parentsguardians and assent from child will be obtained Any parent child who wishes not to participate will allowed doing so
23 Sample size and sampling method All children who were detected to be obese in a previous screening programme will be invited and a minimum sample size of 120 children will be recruited
The sample size is calculated that among obese children a total sample size of 60 participants would detect a between-group difference of 009 BMI SD score units approximately equivalent to a 2 kgm2 difference with 80 power Participant accrual was set at 120 participants to allow as much as 50 percent loss to follow-up However the investigators will take maximum effort to trace the patients
24 Measurements These children will be invited to participate in a follow up programme as part of clinical service as well as research Their parents will be informed to bring their children to the Loins Club of Negambo Host Diabetes Screening and Vocational Training Centre Negambo by appointment
Measurements will be done at the Loins Club of Negambo Host Diabetes Screening and Vocational Training Centre Negamboafter an overnight fast Height weight waist circumference and hip circumference will be measured Percentage fat mass will be measured using Bio Electrical Impedance BIA assay using platform type InBody 230 instrument InBody Biospace South Korea Once the impedance value is measured total body water will be calculated using the locally validated BIA prediction equation Wickramasinghe et al 2008 From Total Body Water TBW Fat Free Mass FFM and hence Fat Mass FM was calculated using age and gender specific water content of FFM Lohman 1989 Blood pressure will be measured using a mercury sphygmomanometer in seated position after 10-15 minute rest Male and female children will be assessed by trained male and female investigators respectively
Metabolic derangements will be assessed by means of total cholesterol LDL-C levels HDL-C levels triglyceride insulin Alanine amino transferase ALT and Aspartate amino transferase AST 8ml of blood into a plain bottle fasting blood sugar 2ml of blood into a NaF containing bottle Oral Glucose Toerance Test OGTT test will be done after giving anhydrous glucose 175g 192g of monohydrous glucose to max of 75g max 825g of monohydrous glucose and blood will be taken 2 hour later for random blood sugar 2ml of blood into a NaF containing bottle and serum insulin 2ml of blood into a plain bottle Serum will be separated immediately and stored at -20 degree of Celcius and analysis will be done at Loins Club of Negambo Host Diabetes Screening and Vocational Training Centre Negambo in batches Blood will be drawn after applying lignocaine Emla anesthetic cream
Insulin resistance will be calculated using Homeostatic model Insulin Resistance HOMA-IR fasting blood sugar fasting insulin 225 Matthews et al 1985 An Ultra sound scan of abdomen will be done to identify hepatic steatosis by a consultant radiologist
Pubertal staging will be assessed using visual charts Morris and Udry 1980 Girls will be shown a diagram depicting different stages of growth of breasts and pubic hair and ask them to match it with their own whenever necessary will seek mothers assistance Similarly boys are shown diagrams of external genitalia and pubic hair and to match with their own The size of the testis will be measure by the examiner using Prader orchidometer If both subject and parents were not sure of the staging with consent the examiner would examine and the correct pubertal stage assessment would be made Measurements and examinations in girls and boys will be carried out by female and male investigators respectively
The whole project will be closely supervised by a two Consultant paediatricians and after the completion of study children who need follow up will be provided the services or if they wish to be followed up at a different institute would be referred with a complete report
25 Randomization Once obesity and overweight is diagnosed and investigated they will be randomly assigned to either of one management protocol on a 11 basis Children will be categorized according to gender and age groups 8-1099 11-1399 14-16 years Using a grid for each age of each sex sequentially they will be allocated to receive management protocol I or II Only the field investigators will have information to the allocation That is Group I Structured diet Physical activity Metformin Group II Structured diet Physical activity Placebo
Dietary advice will be given by a trained nutritionist It will be based on food based dietary guidelines produced by Ministry of Health Jayatissa and Wickramasinghe 2011 Age based portion size guide will be given to parents and children and guide them on the volume they should be eating
Physical activity training will be conducted by a qualified physical activity instructor A daily physical activity routine of 20-30 minutes will be given to each student The programme would be of 3 different types based on their age 11-13 and 14-16 The workout programme will be changed every month in order to break the monotony There will 4 such different workout schedules
Medication 8-1099 year old children will receive metformin Initially children will be given 250mg of metformin daily for a week and increased to 250mg twice daily for a week and then to 500 mg twice daily there after 11-16 year old children will receive 500mg of metformin daily initially for one week which will be increased to 500mg twice daily for a week and then to 1g twice daily Children will be asked to take medication with their morning and evening meals to reduce gastro intestinal side effects and risk of hypoglycaemia Response to medication will be evaluated before each dose revision and will monitor for all possible adverse events
The study will be monitored by a Data and Safety Monitoring Committee comprising of a Paediatrician Paediatric Endocrinologist and a Bio- Statistician
Both the nutritionist and physical trainer will be blinded to the medication children will be receiving
A control group with no treatment will not be employed as it will be unethical not to do any intervention when the diagnosis of obesity is made A placebo is given to overcome any psychological effects of giving medication metformin and Placebo will be manufactured by the State Pharmaceutical Manufacturing Company SPMC The placebo tablet will be similar to metformin in all aspects except for containing the active pharmacological compound
These children will be reviewed two weeks after commencement of therapy and dose will be revised and thereafter monthly in order to ensure compliance and identify any adverse events and address issues In additionally they will be contacted via telephone weekly during first month and fortnightly afterwards to address concernsissues and also to motivate them to keep compliance at a higher level At each of these visits the anthropometry and body composition will be assessed while blood investigations will be repeated at 6 and 12 months At each eveluations one to one meeting will be held
26 Statistics The distribution of metabolic derangements will be described using descriptive statistics Spearman Correlation Coefficients will be used to assess the relationship between percentage fat and metabolic derangements related to NCD as well as anthropometric measurements and metabolic derangements Comparisons of mean values of these measurements will be made using t tests
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None