Ignite Creation Date:
2024-05-06 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 12:50 PM
Study NCT ID:
NCT03610412
Status:
COMPLETED
Last Update Posted:
2022-07-22
First Post:
2018-03-23
Brief Title:
Cinnamomum Cassia Effect on IGF1 and Metabolic Control in Patients With DM2 Without Glycemic Control Metformin Treated
Sponsor:
Coordinación de Investigación en Salud Mexico
Organization:
Coordinación de Investigación en Salud Mexico
Study Overview
Official Title:
Effect of Cinnamomum Cassia as an Enhancer of the Insulin Response of the Insulin-Like Growth Factor-1 and Metabolic Control in Patients With Type 2 Diabetes Mellitus Treated With Metformin Without Glycemic Control
Status:
COMPLETED
Status Verified Date:
2022-07
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:
CICAFAC1
Brief Summary:
Among the multiple treatment options for Diabetes Mellitus Type 2 DM2 the influence on Insuline like growth factor 1 IGF1 plays a causal role in diabetes but has shown similarities with insulin both in its structure and in its function including a rapid reduction in glucose levels in blood could improve glycemic control in patients
Oral administration of 3 g of cinnamomum cassia for 90 days acts as an enhancer of the IGF1 insulin response and on metabolic control fasting glucose glycosylated hemoglobin HbA1c triglycerides total cholesterol high density cholesterol low density cholesterol very low density cholesterol systolic and diastolic blood pressure TAS and TAD body weight in patients with DM2 without glycemic control treated with metformin at doses 850 mg daily
Oral administration of 3 g of cinnamomum cassia for 90 days acts as an enhancer of the IGF1 insulin response and on metabolic control fasting glucose glycosylated hemoglobin HbA1c triglycerides total cholesterol high density cholesterol low density cholesterol very low density cholesterol systolic and diastolic blood pressure TAS and TAD body weight in patients with DM2 without glycemic control treated with metformin at doses 850 mg daily
Detailed Description:
Introduction
DM2 is a chronic disease considered a public health problem scenario in which each year increases the number of people affected has a high prevalence in the investigators country 94 ENSANUT 2016 which causes a high morbidity and mortality Conceptually it is defined as a heterogeneous syndrome originated by the genetic-environmental interaction and characterized by a chronic hyperglycemia as a consequence of a deficiency in the secretion or action of insulin which triggers acute complications ketoacidosis and hyperosmolar coma microvascular chronicles retinopathies and neuropathies and macrovascular coronary heart disease cerebrovascular and peripheral vascular diseases
Growth hormones such as IGF1 with important biological effects on metabolism have been shown to promote the absorption of glucose in certain peripheral tissues It has been shown that IGF1 binds to insulin receptors to stimulate the transport of glucose in fat and muscle inhibiting the production of hepatic glucose by lowering blood glucose while at the same time suppressing insulin secretion increasing sensitivity to insulin and improves the lipid profile
For the treatment of DM2 the use of botanical products can improve glucose metabolism by hypoglycemic effect as well as that of lipids and antioxidant aqueous extracts of cinnamomum cassia have been shown to enhance glucose uptake and glycogen synthesis in vitro and increase phosphorylation of the insulin receptor with possible effect on IGF1 receptor
The emergence of other therapies can generate new treatments for patients with DM2 which in turn reduce costs and help improve the quality of life
Justification
The prevalence of diabetes and metabolic decontrol is high both in Mexico and in the world and conditions the development of long-term complications The concentrations of IGF1 in blood are diminished in the patients with diabetes mellitus and by its effects similar to the insulin in the metabolism of the glucose when normalizing this can produce control of the diabetes
In vitro studies have shown that cinnamomum cassia increases glucose uptake glycogen synthesis and insulin receptor phosphorylation In humans it has been confirmed that it increases the levels of glucagon-like peptide 1 GLP-1 favors the activation of peroxisome proliferator-activated receptor PPAR-γ and PPAR-α promoting insulin sensitivity as well as inhibits hepatic 3-hydroxy 3-methylglutaryl coenzyme A reductase to reduce the synthesis of cholesterol and has a vasodilator effect by activity on the enzyme nitric oxide synthase
Cinnamomum cassia also has a proposal on the signaling of IGF1 receptors GRB2 which activated by phosphatidylinositol 3-kinase PI3K control the proliferation of IGF1 this IGF1 having reduced levels in patients with diabetes becomes a therapeutic target for improved control metabolic However the direct application of IGF1 has as main limitation important collateral effects which has inhibited its use so it is intended to evaluate the stimulatory effect on IGF1 with cinnamomum cassia considering phytopharmaceutical of good quality and low side effects
General hypothesis
Cinnamomum cassia acts as an enhancer of the insulin response of IGF1 and metabolic control in patients with DM2 without glycemic control treated with metformin at low doses
Goals
GENERAL To evaluate the effect of cinnamomum cassia as an enhancer of the insulin response of IGF1 on metabolic control in patients with DM2 without glycemic control treated with metformin
SPECIFIC
To analyze the effect before and after daily oral administration of 850mg of metformin plus 3g of cinnamomum cassia compared to placebo for 90 days on
Levels of IGF1
Fasting glucose value HbA1c triglycerides total cholesterol high density cholesterol low density cholesterol very low density cholesterol systolic and diastolic blood pressure body weight
SECONDARY
To analyze the effect before and after daily oral administration of 850mg of metformin plus 3g of cinnamomum cassia compared to placebo for 90 days on
Insulin sensitivity body mass index BMI waist circumference body fat
Determine the pharmacological attachment and tolerability of CC and placebo
Working universe
Patients with DM2 men and women with a recent diagnosis treated with 850 mg of metformin daily without glycemic control Residents of Guadalajara and metropolitan area and that for the development of the protocol they will go to the facilities of the National Medical Center of the West Specialty Hospital
Sample size
It was calculated according to the following formula for clinical trials n 2 Zα - Z1-β δ d 2 Two working groups will be formed at random which will be integrated as follows 1 a group of 14 patients 7 women and 7 men with DM2 without adequate control treated with metformin 850 mg daily who will receive 1 g of cinnamomum cassia orally every 8 hours for 90 days and 2 a group of 14 patients 7 women and 7 men with DM2 without adequate control treated with metformin 850 mg daily who will receive 1 g of placebo calcined magnesia orally every 8 hours for 90 days In this way the total number of participants required for the study will be at least 28 volunteers
Variables
Independent variable
Pharmacological intervention
Intervention group Administration of metformin 850mg daily and cinnamomum cassia 1g orally before each meal for 90 days
Control group Administration of metformin 850mg daily and of placebo approved 1g calcined magnesia orally before each meal for 90 days
Dependent variables
Primary outcome dependent variables
Laboratory determinations IGF1 fasting glucose HbA1c lipid profile
Clinical determinations systolic and diastolic blood pressure body weight
Dependent secondary outcome variables
Laboratory determinations serum creatinine liver profile
Clinical determinations Insulin sensitivity body mass index waist circumference and percentage of adiposity
Intervening variables
Diet
Exercise and physical activity
Phase of the menstrual cycle
Age
Gender
Clinical procedures
All the anthropometric and vital signs determinations as well as the procedures for the interrogation physical examination and integration of the corresponding clinical history will be carried out by means of universally accepted methods and in accordance with the General Health Law in its Regulation on the Provision of Medical Care Services
The history and clinical exploration will be performed at the first visit of the participant in order to establish eligibility to continue in the study All positive and clinically interesting data will be recorded in the data collection notebook CRD
Paraclinical procedures
During each of the scheduled visits to the research unit it will be necessary to determine a clinical chemistry study for this purpose it will be essential to collect blood samples and their subsequent processing For the collection of all blood samples in each of the visits to the research center all participants will be cited at 800 am and will be an indispensable requirement in each of the collections of samples that come in a fasting state of 12 hours
Once the blood sample has been taken the patient will be given general guidance and recommendations on diet and exercise for a healthy lifestyle From the 3rd visit the attachment to the treatment will be evaluated this determination will be made with the following formula considering as acceptable a value 80
Compliance rate Total number of capsules you ingested Total number of capsules you should have ingested Result multiplied by 100
Quality control in procedures
The quality and information management procedures will have the following quality control strategies
Review of the database in duplicate
Electronic comparison of duplicate database
Statistical review of the quality of the information
Statistical adjustment of the information
Calculation in duplicate of the statistical parameters of quality control
Data management and analysis
Database All participants will have a complete clinical record during the development of the study All the clinical and biochemical data that are submitted to statistical analysis must be registered in the corresponding CRD of each participant The database will be developed from the CRDs according to the coding included in said document in xls format of the Microsoft Excel program Updating and verification of the initial database will be done every time new data is obtained throughout the development of the field work Once all the participants complete all the visits of the field work phase of the study a review verification and final validation of the initial database will be carried out When the absence of errors in the initial database is verified it will be converted to the format for analysis under the statistical package SPSS version 21 or higher for Windows
Statistic analysis
The most appropriate and reliable statistical procedures for the analysis of the data will be decided based on the result of the normality test Overall the descriptive statistics used in the presentation of the data will include qualitative measures in frequency and percentage and quantitative measures of central tendency and dispersion arithmetic mean and standard deviation when considered appropriate it will also include median minimum and maximum values or dispersion ranges
For all cases the significance will be p 005 All patients receiving at least one dose of intervention treatment will be taken into account in the statistical analysis as part of the intention-to-treat analysis of the eliminated subjects
Ethical and legal framework
All the procedures and activities carried out during the development of this clinical trial will be carried out in full compliance with the legal provisions of the General Health Law of the United Mexican States and in accordance with the ethical principles for pharmacological research on human beings detailed in the latest revision of the Helsinki Declaration and the International Harmonization Conference
The research protocol will be submitted for approval by the local Research Committee of the Specialties Hospital of the National Medical Center of the West The study is classified within the General Health Law and its regulations on research in humans as of risk greater than the minimum since it is a pharmacological study with potential risk for which it is required to obtain a consent under written information signed at the beginning of the study The document will be signed in duplicate by the participant two witnesses from outside the research team and preferably relatives or friends of the participant and by the principal investigator of the center One of the duplicates of informed consent will remain with the principal investigator while the other will be delivered to the study participant
According to the guidelines of good clinical practice all participants in the study will be identified only by initials and number in the database The records and laboratory results will be available only to the principal investigators and with the restrictions of law for the participant
Conflicts of interest
There are no conflicts of interest for the conduct of the study The information obtained from this study will be made available to privileged researchers involved in the development of it
DM2 is a chronic disease considered a public health problem scenario in which each year increases the number of people affected has a high prevalence in the investigators country 94 ENSANUT 2016 which causes a high morbidity and mortality Conceptually it is defined as a heterogeneous syndrome originated by the genetic-environmental interaction and characterized by a chronic hyperglycemia as a consequence of a deficiency in the secretion or action of insulin which triggers acute complications ketoacidosis and hyperosmolar coma microvascular chronicles retinopathies and neuropathies and macrovascular coronary heart disease cerebrovascular and peripheral vascular diseases
Growth hormones such as IGF1 with important biological effects on metabolism have been shown to promote the absorption of glucose in certain peripheral tissues It has been shown that IGF1 binds to insulin receptors to stimulate the transport of glucose in fat and muscle inhibiting the production of hepatic glucose by lowering blood glucose while at the same time suppressing insulin secretion increasing sensitivity to insulin and improves the lipid profile
For the treatment of DM2 the use of botanical products can improve glucose metabolism by hypoglycemic effect as well as that of lipids and antioxidant aqueous extracts of cinnamomum cassia have been shown to enhance glucose uptake and glycogen synthesis in vitro and increase phosphorylation of the insulin receptor with possible effect on IGF1 receptor
The emergence of other therapies can generate new treatments for patients with DM2 which in turn reduce costs and help improve the quality of life
Justification
The prevalence of diabetes and metabolic decontrol is high both in Mexico and in the world and conditions the development of long-term complications The concentrations of IGF1 in blood are diminished in the patients with diabetes mellitus and by its effects similar to the insulin in the metabolism of the glucose when normalizing this can produce control of the diabetes
In vitro studies have shown that cinnamomum cassia increases glucose uptake glycogen synthesis and insulin receptor phosphorylation In humans it has been confirmed that it increases the levels of glucagon-like peptide 1 GLP-1 favors the activation of peroxisome proliferator-activated receptor PPAR-γ and PPAR-α promoting insulin sensitivity as well as inhibits hepatic 3-hydroxy 3-methylglutaryl coenzyme A reductase to reduce the synthesis of cholesterol and has a vasodilator effect by activity on the enzyme nitric oxide synthase
Cinnamomum cassia also has a proposal on the signaling of IGF1 receptors GRB2 which activated by phosphatidylinositol 3-kinase PI3K control the proliferation of IGF1 this IGF1 having reduced levels in patients with diabetes becomes a therapeutic target for improved control metabolic However the direct application of IGF1 has as main limitation important collateral effects which has inhibited its use so it is intended to evaluate the stimulatory effect on IGF1 with cinnamomum cassia considering phytopharmaceutical of good quality and low side effects
General hypothesis
Cinnamomum cassia acts as an enhancer of the insulin response of IGF1 and metabolic control in patients with DM2 without glycemic control treated with metformin at low doses
Goals
GENERAL To evaluate the effect of cinnamomum cassia as an enhancer of the insulin response of IGF1 on metabolic control in patients with DM2 without glycemic control treated with metformin
SPECIFIC
To analyze the effect before and after daily oral administration of 850mg of metformin plus 3g of cinnamomum cassia compared to placebo for 90 days on
Levels of IGF1
Fasting glucose value HbA1c triglycerides total cholesterol high density cholesterol low density cholesterol very low density cholesterol systolic and diastolic blood pressure body weight
SECONDARY
To analyze the effect before and after daily oral administration of 850mg of metformin plus 3g of cinnamomum cassia compared to placebo for 90 days on
Insulin sensitivity body mass index BMI waist circumference body fat
Determine the pharmacological attachment and tolerability of CC and placebo
Working universe
Patients with DM2 men and women with a recent diagnosis treated with 850 mg of metformin daily without glycemic control Residents of Guadalajara and metropolitan area and that for the development of the protocol they will go to the facilities of the National Medical Center of the West Specialty Hospital
Sample size
It was calculated according to the following formula for clinical trials n 2 Zα - Z1-β δ d 2 Two working groups will be formed at random which will be integrated as follows 1 a group of 14 patients 7 women and 7 men with DM2 without adequate control treated with metformin 850 mg daily who will receive 1 g of cinnamomum cassia orally every 8 hours for 90 days and 2 a group of 14 patients 7 women and 7 men with DM2 without adequate control treated with metformin 850 mg daily who will receive 1 g of placebo calcined magnesia orally every 8 hours for 90 days In this way the total number of participants required for the study will be at least 28 volunteers
Variables
Independent variable
Pharmacological intervention
Intervention group Administration of metformin 850mg daily and cinnamomum cassia 1g orally before each meal for 90 days
Control group Administration of metformin 850mg daily and of placebo approved 1g calcined magnesia orally before each meal for 90 days
Dependent variables
Primary outcome dependent variables
Laboratory determinations IGF1 fasting glucose HbA1c lipid profile
Clinical determinations systolic and diastolic blood pressure body weight
Dependent secondary outcome variables
Laboratory determinations serum creatinine liver profile
Clinical determinations Insulin sensitivity body mass index waist circumference and percentage of adiposity
Intervening variables
Diet
Exercise and physical activity
Phase of the menstrual cycle
Age
Gender
Clinical procedures
All the anthropometric and vital signs determinations as well as the procedures for the interrogation physical examination and integration of the corresponding clinical history will be carried out by means of universally accepted methods and in accordance with the General Health Law in its Regulation on the Provision of Medical Care Services
The history and clinical exploration will be performed at the first visit of the participant in order to establish eligibility to continue in the study All positive and clinically interesting data will be recorded in the data collection notebook CRD
Paraclinical procedures
During each of the scheduled visits to the research unit it will be necessary to determine a clinical chemistry study for this purpose it will be essential to collect blood samples and their subsequent processing For the collection of all blood samples in each of the visits to the research center all participants will be cited at 800 am and will be an indispensable requirement in each of the collections of samples that come in a fasting state of 12 hours
Once the blood sample has been taken the patient will be given general guidance and recommendations on diet and exercise for a healthy lifestyle From the 3rd visit the attachment to the treatment will be evaluated this determination will be made with the following formula considering as acceptable a value 80
Compliance rate Total number of capsules you ingested Total number of capsules you should have ingested Result multiplied by 100
Quality control in procedures
The quality and information management procedures will have the following quality control strategies
Review of the database in duplicate
Electronic comparison of duplicate database
Statistical review of the quality of the information
Statistical adjustment of the information
Calculation in duplicate of the statistical parameters of quality control
Data management and analysis
Database All participants will have a complete clinical record during the development of the study All the clinical and biochemical data that are submitted to statistical analysis must be registered in the corresponding CRD of each participant The database will be developed from the CRDs according to the coding included in said document in xls format of the Microsoft Excel program Updating and verification of the initial database will be done every time new data is obtained throughout the development of the field work Once all the participants complete all the visits of the field work phase of the study a review verification and final validation of the initial database will be carried out When the absence of errors in the initial database is verified it will be converted to the format for analysis under the statistical package SPSS version 21 or higher for Windows
Statistic analysis
The most appropriate and reliable statistical procedures for the analysis of the data will be decided based on the result of the normality test Overall the descriptive statistics used in the presentation of the data will include qualitative measures in frequency and percentage and quantitative measures of central tendency and dispersion arithmetic mean and standard deviation when considered appropriate it will also include median minimum and maximum values or dispersion ranges
For all cases the significance will be p 005 All patients receiving at least one dose of intervention treatment will be taken into account in the statistical analysis as part of the intention-to-treat analysis of the eliminated subjects
Ethical and legal framework
All the procedures and activities carried out during the development of this clinical trial will be carried out in full compliance with the legal provisions of the General Health Law of the United Mexican States and in accordance with the ethical principles for pharmacological research on human beings detailed in the latest revision of the Helsinki Declaration and the International Harmonization Conference
The research protocol will be submitted for approval by the local Research Committee of the Specialties Hospital of the National Medical Center of the West The study is classified within the General Health Law and its regulations on research in humans as of risk greater than the minimum since it is a pharmacological study with potential risk for which it is required to obtain a consent under written information signed at the beginning of the study The document will be signed in duplicate by the participant two witnesses from outside the research team and preferably relatives or friends of the participant and by the principal investigator of the center One of the duplicates of informed consent will remain with the principal investigator while the other will be delivered to the study participant
According to the guidelines of good clinical practice all participants in the study will be identified only by initials and number in the database The records and laboratory results will be available only to the principal investigators and with the restrictions of law for the participant
Conflicts of interest
There are no conflicts of interest for the conduct of the study The information obtained from this study will be made available to privileged researchers involved in the development of it
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