Ignite Creation Date:
2024-05-06 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 12:49 PM
Study NCT ID:
NCT03591900
Status:
COMPLETED
Last Update Posted:
2018-07-19
First Post:
2016-06-21
Brief Title:
The Use of CGMS to Detect Alterations of Blood Glucose in Thalassemic Patients
Sponsor:
Ain Shams University
Organization:
Ain Shams University
Study Overview
Official Title:
Evaluation of Continuous Blood Glucose Monitoring Method for Detection of Alterations in Glucose Homeostasis in Beta Thalassemia Patients
Status:
COMPLETED
Status Verified Date:
2018-07
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 the study is to
Assess the pattern of glucose homeostasis in patients with B thalassemia
To detect early impairment in glucose metabolism and prediabetic state in B thalassemia patients using continuous glucose monitoring system
To study the prevalence and type of DM in B thalassemia patients
A comparative study of standard insulin therapy compared to insulin pump therapy in thalassemic diabetic patients will be done
The study will include screening of 200 children and adolescents who are regularly attending the Hematology Oncology Clinic and fulfilling the inclusion criteria for abnormalities of glucose homeostasis
A pilot study will be done on 15 patients with abnormal glucose tolerance which will include
A-Continuous glucose monitoring system CGMS A glucometer will be given to each patient and will be asked to measure blood glucose before meals and snacks and record the valus in the CGMS for better calibration
B-Therapeutic intervention
Thalassemia patients who proved to have diabetes according to the ADA criteria will be subjected to
Insulin pump will be tried in each diabetic thalassemic patient versus conventional insulin therapy
Assess the pattern of glucose homeostasis in patients with B thalassemia
To detect early impairment in glucose metabolism and prediabetic state in B thalassemia patients using continuous glucose monitoring system
To study the prevalence and type of DM in B thalassemia patients
A comparative study of standard insulin therapy compared to insulin pump therapy in thalassemic diabetic patients will be done
The study will include screening of 200 children and adolescents who are regularly attending the Hematology Oncology Clinic and fulfilling the inclusion criteria for abnormalities of glucose homeostasis
A pilot study will be done on 15 patients with abnormal glucose tolerance which will include
A-Continuous glucose monitoring system CGMS A glucometer will be given to each patient and will be asked to measure blood glucose before meals and snacks and record the valus in the CGMS for better calibration
B-Therapeutic intervention
Thalassemia patients who proved to have diabetes according to the ADA criteria will be subjected to
Insulin pump will be tried in each diabetic thalassemic patient versus conventional insulin therapy
Detailed Description:
β-thalassemia is a worldwide distributed monogenic red cell disorder characterized by the absence or reduced β-globin chain synthesis De Franceschi et al2013
Approximately 7 of the global population is carrier of such disorders and 300000-400000 babies with severe forms of these diseases are born each year Weatherall 2005 Modell et al 2008 Severe hereditary hemoglobin disorders of red cells occur at highest frequency in tropical regions
Hemoglobinopathies constitute the single most common monogenic defect worldwide and among hemoglobin disorders the thalassemias prominently contribute to Weatherall et al 2001 de Franceschi et al 2011 β-thalassemias β-thal are characterized by the presence of mutations on beta-globin gene resulting in the absence or reduced synthesis of β-globin chains
Glucose metabolism disturbances among other endocrinopathies are a common feature of β -thalassaemia Pancreatic iron overload and diabetes mellitus DM are common in thalassemia major patients However the relationship between iron stores and glucose disturbances is not well defined Leila et al 2012
The etiology of DM in β -thalassemia is suggested to be due to the effect of iron overload on the different tissues controlling the carbohydrate homeostatic mechanisms including the pancreas and liver However controversy about the etiology of this glycemic abnormality still exists Weinberg 2007
Both insulin deficiency and insulin resistance are reported in patients with β -thalassemia Suggested risk factors for development of DM in patients with β -thalassemia include old age increased amount of blood transfusion high serum ferritin level family history of DM hepatic impairment and genetic modifiers of iron overload Cario et al 2003Suvarna et al 2006 Weinberg 2007
Patients with DM had significantly impaired insulin sensitivity and insulin release Bergman et al 2010 Traditionally insulin deficiency and long-standing insulin resistance De Sanctis et al 1988 Pappas et al 1996 that result from direct toxic damage by iron to pancreatic-beta cells are thought to be the main underlying mechanisms leading from mild glucose intolerance to overt diabetes As these endocrine complications result from chronic iron overload they are much more common in patients whose chelation therapy is insufficient Farmaki et al 2006
Greater chelation options have improved survival Chouliaras et al 2011 however many patients still carry dangerous extrahepatic iron burdens As patients live longer cumulative iron-mediated toxicity compounded by natural aging makes diabetes a significant clinical problem
Pancreatic iron loading in thalassemia major patients begins in early childhood and the overall prevalence of diabetes mellitus DM ranges from 64 to 141 on cross-sectional studies Borgna-Pignatti et al 2004 Vogiatzi et al 2009 Both insulin resistance and decreased insulin secretion contribute to diabetes in thalassemia major patients Angelopoulos et al 2006 Cario et al 2003 Hafez 2009
Diabetes prevalence in thalassemia has been shown to correlate with serum ferritin Jaruratanasirikul et al 2008 Siklar et al 2008 with hepatitis C infection Chern 2001 Sougleri et al 2001Mowla et al 2004 and with pancreatic and cardiac iron Au et al 2007 Matter et al 2010
Insulin pump therapy in the form of continuous subcutaneous insulin infusion CSII was introduced in the 1970s and turned out to ensure better metabolic control of diabetes compared to traditional insulin therapy approaches It is currently considered to be the optimal method of insulin administration since it imitates the pancreatic activity in the best possible way ensures precise dosage and at the same time offers a high level of ease and comfort Bruttomesso D et al 2009 Danne T et al 2008
Compared to the traditional methods of insulin therapy by means of multiple daily insulin injections MDI CSII can significantly decrease glycated hemoglobin HbA1C reduce 24-hour glucose variability decrease incidence of severe hypoglycemia and eliminate dawn phenomenon Moreover the use of CSII is associated with improved quality of life and precise insulin administration with respect to physical effort and dietJeitler K et al 2008 Phillip M et al 2007
A long-term effect of CSII on the control of diabetes mellitus in thalassemics needs to be explained Hammond P 2004
Aim of the work
The aim of the study is to
Assess the pattern of glucose homeostasis in patients with B thalassemia
To detect early impairment in glucose metabolism and prediabetic state in B thalassemia patients using continuous glucose monitoring system
To study the prevalence and type of DM in B thalassemia patients
A comparative study of standard insulin therapy compared to insulin pump therapy in thalassemic diabetic patients will be done
Patients and methods
Subjects
The study will include screening of 200 children and adolescents who are regularly attending the Hematology Oncology Clinic and fulfilling the inclusion criteria for abnormalities of glucose homeostasis ADA criteria for diagnosing diabetes mellitus impaired glucose tolerance American Diabetes Association 2013
1 Diabetes symptoms ie polyuria polydipsia and unexplained weight loss plus
a random venous plasma glucose concentration 126 mgdl 70 mmoll or
a fasting plasma glucose concentration 126 mgdl 70 mmoll whole blood 61mmoll or
two hour plasma glucose concentration 200 mgdl 111 mmoll two hours after 75g anhydrous glucose in an oral glucose tolerance test OGTT
2 With no symptoms diagnosis should not be based on a single glucose determination but requires confirmatory plasma venous determination At least one additional glucose test result on another day with a value in the diabetic range is essential either fasting from a random sample or from the two hour post glucose load If the fasting or random values are not diagnostic the two hour value should be used
Impaired Glucose Tolerance IGT is a stage of impaired glucose regulation Fasting plasma glucose 70 mmol and OGTT two hour value 78mmoll but 111 mmoll
Impaired Fasting Glycaemia IFG has been introduced to classify individuals who have fasting glucose values above the normal range but below those diagnostic of diabetes Fasting plasma glucose 61 mmoll but 70 mmoll American Diabetes Patients proved to be diabetics according to the ADA criteria will be subjected to therapeutic intervention
An informed consent will be obtained from each patient or his legal guardian before enrollement in the study
A- Screening and recruitment stage
All included patients will be subjected to the following
1 Detailed medical history taking with special stress on
Demographic data name age sex consanguinity and socioeconomic class
Age of diagnosis of thalassemia and disease duration
Transfusion history
Age of first transfusion
Amount of blood in each transfusion
Type of transfused PRBCs filtered washed untreated
Frequency of transfusion
Calculation of transfusion index packed red cell per body weight in Kg per year
Iron chelation therapyType dose duration complications and compliance to chelation therapy Compliance will be assessed by reviewing patient self-report of dose-taking and the appropriate number of doses taken during each day will be checked by prescription refills and pill count Claxton et al 2001
History of spleenectomy
History of viral hepatitis hepatitis B and C virus
2 Thorough clinical examination laying stress on
Assessment of anthropometric measures including weight in kilograms Kg and height in centimeters cm and plotting them on the age- and sex-standard percentiles according to Egyptian growth charts Diabetic endocrine and metabolic pediatric unit 2003 Body mass index BMI will be measured as kgm2 Guldiken et al 2007
Measurement of vital data including heart rate and blood pressure
BMI simple index of weight-for-height that is commonly used to classify underweight overweight and obesity It is calculated as the weight in kilograms divided by the square of the height in meters Kgm2 WHO 1995
Complete examination including cardiac chest abdominal and neurological examination
Assessment of sexual maturity using Tanner score Vichinsky et al 2008
Delayed puberty and hypogonadism Defined as absence of sexual characteristics in girls above the age of 13 years and a testicular volume 4ml in boys above the age of 14 years Arrested puberty is the non-progression of puberty for a period of 12 months Arya et al 2005
3 Laboratory investigations including
Complete blood picture CBC using Sysmex XT-1800i Sysmex Japan with examination of Leishman-stained smears for red blood cells RBC morphology and differential white blood cell WBC count
Peripheral blood staining by brilliant cresyl blue and examination of a smear for reticulocytic count
Qualitative and quantitative hemoglobin analysis at time of diagnosis collected from follow up sheets of patients
Hb electrophoresis to ensure diagnosis of B thalassemia
Measurement of serum ferritinSoliman AT et al 2013
Measurement of fasting C peptide
Measurement of random and fasting plasma glucose levelAmerican Diabetes Association 2013
Oral glucose tolerance test Thennadil SN et al 2001
A pilot study will be done on 15 patients with abnormal glucose tolerance which will include
A-Continuous glucose monitoring system CGMS A glucometer will be given to each patient and will be asked to measure blood glucose before meals and snacks and record the valus in the CGMS for better calibration Khammar A et al 2009
B-Therapeutic intervention
Thalassemia patients who proved to have diabetes according to the ADA criteria will be subjected to
Insulin pump will be tried in each diabetic thalassemic patient versus conventional insulin therapyBruttomesso D et al 2009
Approximately 7 of the global population is carrier of such disorders and 300000-400000 babies with severe forms of these diseases are born each year Weatherall 2005 Modell et al 2008 Severe hereditary hemoglobin disorders of red cells occur at highest frequency in tropical regions
Hemoglobinopathies constitute the single most common monogenic defect worldwide and among hemoglobin disorders the thalassemias prominently contribute to Weatherall et al 2001 de Franceschi et al 2011 β-thalassemias β-thal are characterized by the presence of mutations on beta-globin gene resulting in the absence or reduced synthesis of β-globin chains
Glucose metabolism disturbances among other endocrinopathies are a common feature of β -thalassaemia Pancreatic iron overload and diabetes mellitus DM are common in thalassemia major patients However the relationship between iron stores and glucose disturbances is not well defined Leila et al 2012
The etiology of DM in β -thalassemia is suggested to be due to the effect of iron overload on the different tissues controlling the carbohydrate homeostatic mechanisms including the pancreas and liver However controversy about the etiology of this glycemic abnormality still exists Weinberg 2007
Both insulin deficiency and insulin resistance are reported in patients with β -thalassemia Suggested risk factors for development of DM in patients with β -thalassemia include old age increased amount of blood transfusion high serum ferritin level family history of DM hepatic impairment and genetic modifiers of iron overload Cario et al 2003Suvarna et al 2006 Weinberg 2007
Patients with DM had significantly impaired insulin sensitivity and insulin release Bergman et al 2010 Traditionally insulin deficiency and long-standing insulin resistance De Sanctis et al 1988 Pappas et al 1996 that result from direct toxic damage by iron to pancreatic-beta cells are thought to be the main underlying mechanisms leading from mild glucose intolerance to overt diabetes As these endocrine complications result from chronic iron overload they are much more common in patients whose chelation therapy is insufficient Farmaki et al 2006
Greater chelation options have improved survival Chouliaras et al 2011 however many patients still carry dangerous extrahepatic iron burdens As patients live longer cumulative iron-mediated toxicity compounded by natural aging makes diabetes a significant clinical problem
Pancreatic iron loading in thalassemia major patients begins in early childhood and the overall prevalence of diabetes mellitus DM ranges from 64 to 141 on cross-sectional studies Borgna-Pignatti et al 2004 Vogiatzi et al 2009 Both insulin resistance and decreased insulin secretion contribute to diabetes in thalassemia major patients Angelopoulos et al 2006 Cario et al 2003 Hafez 2009
Diabetes prevalence in thalassemia has been shown to correlate with serum ferritin Jaruratanasirikul et al 2008 Siklar et al 2008 with hepatitis C infection Chern 2001 Sougleri et al 2001Mowla et al 2004 and with pancreatic and cardiac iron Au et al 2007 Matter et al 2010
Insulin pump therapy in the form of continuous subcutaneous insulin infusion CSII was introduced in the 1970s and turned out to ensure better metabolic control of diabetes compared to traditional insulin therapy approaches It is currently considered to be the optimal method of insulin administration since it imitates the pancreatic activity in the best possible way ensures precise dosage and at the same time offers a high level of ease and comfort Bruttomesso D et al 2009 Danne T et al 2008
Compared to the traditional methods of insulin therapy by means of multiple daily insulin injections MDI CSII can significantly decrease glycated hemoglobin HbA1C reduce 24-hour glucose variability decrease incidence of severe hypoglycemia and eliminate dawn phenomenon Moreover the use of CSII is associated with improved quality of life and precise insulin administration with respect to physical effort and dietJeitler K et al 2008 Phillip M et al 2007
A long-term effect of CSII on the control of diabetes mellitus in thalassemics needs to be explained Hammond P 2004
Aim of the work
The aim of the study is to
Assess the pattern of glucose homeostasis in patients with B thalassemia
To detect early impairment in glucose metabolism and prediabetic state in B thalassemia patients using continuous glucose monitoring system
To study the prevalence and type of DM in B thalassemia patients
A comparative study of standard insulin therapy compared to insulin pump therapy in thalassemic diabetic patients will be done
Patients and methods
Subjects
The study will include screening of 200 children and adolescents who are regularly attending the Hematology Oncology Clinic and fulfilling the inclusion criteria for abnormalities of glucose homeostasis ADA criteria for diagnosing diabetes mellitus impaired glucose tolerance American Diabetes Association 2013
1 Diabetes symptoms ie polyuria polydipsia and unexplained weight loss plus
a random venous plasma glucose concentration 126 mgdl 70 mmoll or
a fasting plasma glucose concentration 126 mgdl 70 mmoll whole blood 61mmoll or
two hour plasma glucose concentration 200 mgdl 111 mmoll two hours after 75g anhydrous glucose in an oral glucose tolerance test OGTT
2 With no symptoms diagnosis should not be based on a single glucose determination but requires confirmatory plasma venous determination At least one additional glucose test result on another day with a value in the diabetic range is essential either fasting from a random sample or from the two hour post glucose load If the fasting or random values are not diagnostic the two hour value should be used
Impaired Glucose Tolerance IGT is a stage of impaired glucose regulation Fasting plasma glucose 70 mmol and OGTT two hour value 78mmoll but 111 mmoll
Impaired Fasting Glycaemia IFG has been introduced to classify individuals who have fasting glucose values above the normal range but below those diagnostic of diabetes Fasting plasma glucose 61 mmoll but 70 mmoll American Diabetes Patients proved to be diabetics according to the ADA criteria will be subjected to therapeutic intervention
An informed consent will be obtained from each patient or his legal guardian before enrollement in the study
A- Screening and recruitment stage
All included patients will be subjected to the following
1 Detailed medical history taking with special stress on
Demographic data name age sex consanguinity and socioeconomic class
Age of diagnosis of thalassemia and disease duration
Transfusion history
Age of first transfusion
Amount of blood in each transfusion
Type of transfused PRBCs filtered washed untreated
Frequency of transfusion
Calculation of transfusion index packed red cell per body weight in Kg per year
Iron chelation therapyType dose duration complications and compliance to chelation therapy Compliance will be assessed by reviewing patient self-report of dose-taking and the appropriate number of doses taken during each day will be checked by prescription refills and pill count Claxton et al 2001
History of spleenectomy
History of viral hepatitis hepatitis B and C virus
2 Thorough clinical examination laying stress on
Assessment of anthropometric measures including weight in kilograms Kg and height in centimeters cm and plotting them on the age- and sex-standard percentiles according to Egyptian growth charts Diabetic endocrine and metabolic pediatric unit 2003 Body mass index BMI will be measured as kgm2 Guldiken et al 2007
Measurement of vital data including heart rate and blood pressure
BMI simple index of weight-for-height that is commonly used to classify underweight overweight and obesity It is calculated as the weight in kilograms divided by the square of the height in meters Kgm2 WHO 1995
Complete examination including cardiac chest abdominal and neurological examination
Assessment of sexual maturity using Tanner score Vichinsky et al 2008
Delayed puberty and hypogonadism Defined as absence of sexual characteristics in girls above the age of 13 years and a testicular volume 4ml in boys above the age of 14 years Arrested puberty is the non-progression of puberty for a period of 12 months Arya et al 2005
3 Laboratory investigations including
Complete blood picture CBC using Sysmex XT-1800i Sysmex Japan with examination of Leishman-stained smears for red blood cells RBC morphology and differential white blood cell WBC count
Peripheral blood staining by brilliant cresyl blue and examination of a smear for reticulocytic count
Qualitative and quantitative hemoglobin analysis at time of diagnosis collected from follow up sheets of patients
Hb electrophoresis to ensure diagnosis of B thalassemia
Measurement of serum ferritinSoliman AT et al 2013
Measurement of fasting C peptide
Measurement of random and fasting plasma glucose levelAmerican Diabetes Association 2013
Oral glucose tolerance test Thennadil SN et al 2001
A pilot study will be done on 15 patients with abnormal glucose tolerance which will include
A-Continuous glucose monitoring system CGMS A glucometer will be given to each patient and will be asked to measure blood glucose before meals and snacks and record the valus in the CGMS for better calibration Khammar A et al 2009
B-Therapeutic intervention
Thalassemia patients who proved to have diabetes according to the ADA criteria will be subjected to
Insulin pump will be tried in each diabetic thalassemic patient versus conventional insulin therapyBruttomesso D et al 2009
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