Ignite Creation Date:
2024-05-19 @ 5:33 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06410352
Status:
RECRUITING
Last Update Posted:
2024-05-13
First Post:
2024-04-29
Brief Title:
Effectiveness of Weight Loss Methods on Lifespan for Metabolic Syndrome
Sponsor:
University Medical Center Kazakhstan
Organization:
University Medical Center Kazakhstan
Study Overview
Official Title:
Effectiveness of Pharmacologic Surgical and Dietetic Weight Loss Methods on Lifespan in Patients With Metabolic Syndrome a Comparative Clinical Trial
Status:
RECRUITING
Status Verified Date:
2024-05
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:
Background The prevalence of type 2 diabetes mellitus T2D in the world is constantly increasing Treatment of T2D is complicated by arterial hypertension and obesity metabolic syndrome - MS Cardiovascular complications are the main cause of death in patients with MS Objective weight loss improves clinical and laboratory parameters in patients with T2D and hypertension
Purpose To study lifespan glycemic and lipid metabolism quality of life and cost-effectiveness of pharmacologic surgical and dietetic weight loss methods in obese patients with MS at 24 weeks in a comparative clinical trial
Methods
1 st stage - Study design An open pilot prospective clinical trial The study included 71 adult patients with T2D and hypertension for the Ramadan fasts RF weight loss
2 nd stage - Study design A 24-week open label prospective multicenter comparative clinical trial with the intention-to-treat analysis
Participants Totally 150 adult patients with MS aged 35-65 years and with BMI27 kgm2 for Asian will be included They will be distributed in three comparative groups drug treatment surgery and diet
Primary endpoints weight loss fasting blood glucose blood insulin level systolicdiastolic BP
Secondary endpoints blood lipids heel bone mineral density HBMD and ejection fraction EF
Expected results
A prospective multicenter clinical study will provide comparative results on life expectancy glycemic and lipid metabolism quality of life cost-effectiveness of pharmacological bariatric and dietary methods of weight loss in patients with obesity T2D and hypertension As a result of the research the following will be published
1 at least three articles andor reviews in peer-reviewed scientific publications indexed in the Science Citation Index Expanded of the Web Of Science database andor having a Cite Score percentile in the Scopus of at least 50
2 at least 1 patent for an invention including a positive decision on it
Purpose To study lifespan glycemic and lipid metabolism quality of life and cost-effectiveness of pharmacologic surgical and dietetic weight loss methods in obese patients with MS at 24 weeks in a comparative clinical trial
Methods
1 st stage - Study design An open pilot prospective clinical trial The study included 71 adult patients with T2D and hypertension for the Ramadan fasts RF weight loss
2 nd stage - Study design A 24-week open label prospective multicenter comparative clinical trial with the intention-to-treat analysis
Participants Totally 150 adult patients with MS aged 35-65 years and with BMI27 kgm2 for Asian will be included They will be distributed in three comparative groups drug treatment surgery and diet
Primary endpoints weight loss fasting blood glucose blood insulin level systolicdiastolic BP
Secondary endpoints blood lipids heel bone mineral density HBMD and ejection fraction EF
Expected results
A prospective multicenter clinical study will provide comparative results on life expectancy glycemic and lipid metabolism quality of life cost-effectiveness of pharmacological bariatric and dietary methods of weight loss in patients with obesity T2D and hypertension As a result of the research the following will be published
1 at least three articles andor reviews in peer-reviewed scientific publications indexed in the Science Citation Index Expanded of the Web Of Science database andor having a Cite Score percentile in the Scopus of at least 50
2 at least 1 patent for an invention including a positive decision on it
Detailed Description:
At the 1 st stage of the study will screen 71 adult patients for eligibility aged 35 to 65 years with T2D and hypertension for the RF T2D was treated with Metformin Sulfonylurea GLP-1 agonists exenatide liraglutide Glitazones in different combinations hypertension was treated with beta-blockers calcium channel blockers diuretics SGLT-2 Inhibitors empagliflozin canagliflozin in different combinations Patients with heart failure HF in their medical records and anamnesis with reduced ejection fraction 55 also will be included I-II stages of the NYHA functional classification
Inclusion criteria 1 written informed consent 2 35 age 65 years old 2 any BMI and WC 3 diagnosis of T2D and hypertension 3 years and treatment with non-hormonal conventional pharmacological medications 4 any level of triglycerides cholesterol body fat 5 weight loss on the RF for 30 days
Exclusion criteria 1 age 35 or 65 years old 1 Insulin-depended T2D and uncontrolled high BP 2 patients taking gastrointestinal lipase inhibitors etc 3 presence of acute infection diseases or exacerbation of chronic diseases 4 ejection fraction 30 5 history of alcohol consumption 30 gday within the past 5 years 6 malignancy within the past 5 years gestation or lactation kidney failure hereditary diseases or known hypersensitivity to any of the test substances
Outcome measures Primary endpoints weight loss fasting blood glucose blood insulin level systolicdiastolic BP Secondary endpoints blood lipids heel bone mineral density HBMD and EF
Intervention The participants adhered to fasting on RF season They strictly adhered to two principles of nutrition during RF 1 no blood no smell of fat which means dont eat meat and dont eat fatty foods 2 the Sehri time a meal eaten before dawn included just 15-20 glass of water and fruits of 80-100 gr apple dates and persimmon Indeed the patients followed a diet in which they ate one meal a day - participants have a meal during Iftar time a meal eaten after sunset The participants also adhered to walking at least 3000 stepsday sexual self-restraint
A combination of in-person conversations and telephone calls conductes during the 30-day study period the baseline7-day14-day and 30-day RF
At the 2nd stage of the study will include totally 150 adult patients with MS distributed in three comparative groups drug treatment surgery and diet therapy
The study design is prospective because the investigators have to comparatively measure TL beforeafter interventions the study may not be an observation study Because of the trial will non-randomized patients will be allocated to each group based on equal baseline characteristics according to the inclusionexclusion criteria and including adjustments for baseline and confounding characteristics
The patients will be allocated to each group based on the patient and two physicians surgeon and therapist decisions to avoid the risk of selection bias Normalization of parameters will focuse on the work required to embed processes into statistics
Inclusion criteria 1 written informed consent 2 T2D3-year with glucose lowering therapy including insulin 3 35-55 years old 4 BMI27 kgm2 for both sex for Asian ethnicity 5 ongoing treatment with antihypertensive treatment 6 weight loss 15-20 at baseline and dynamic follow-up up to 24 weeks
All included patients before recruiting to the study received standard-of-care treatment for T2D and AH according to regional guidelines
Exclusion criteria T1D 34 age 56 years old unstable cardiac disorders New York Heart Association class IV heart failure refractory angina uncontrolled arrhythmias critical valvular heart disease or severe uncontrolled hypertension glomerular filtration rate 30 mLmin andor dialysis within 14 days before screening malignancy within the past 5 years gestation or lactation hereditary diseases known hypersensitivity to any of the test substances
The 1st group n50 receives subcutaneous Semaglutide GLP-1RA 1 mg once a 7 day with oral Empagliflozin SGLT-2i 25 mg once a day that is a novel combination additionally to standard medical treatment including anti-diabetes antihypertensive lipid-lowering symptomatic therapy
The 2nd group n50 receives surgical method laparoscopic MGB These patients pass through additional pre-operation examination blood tests and electrocardiography esophagogastroscopy ultrasound and other necessary standard methods
The 3rd group n50 receives very-low-calorie-restriction diet Analimentary-detoxication including 100 kcalday with fat-free vegetables tomatocucumber and salt intake 5-6 gday optimum physical activity and sexual self-restraint The program goals the next outputs a use of own fatty store b control endogen intoxication c reuse of interim metabolic substrates
A combination of in-person conversations and telephone calls conduct during the study period
Justification of the sample size The estimated treatment difference will set to 10 with a standard deviation of 8 and the superiority margin of 5 δ005 based on two-sided hypothesis testing Using SPSSSample-PowerV230 the number of evaluable individuals needed per treatment arm 32 At least 150 patients will be screened and recruited in the comparative clinical trial
End Points The primary endpoints reduction in body weight 15-20 from baseline leukocyte TL The secondary endpoints HbA1c fasting blood glucose and 2-hour oral glucose tolerance test OGTT systolicdiastolic BP lipid profile immunoassay insulin in blood adverse events
Methods
Criteria for the diagnosis of MS Diagnosis of MS IDF-2005 Diagnosis T2D HbA1c65 fasting plasma glucose level 70 mmoll or a patient receives antidiabetic therapy ADA 2023 55 AH systolic-BP130 andor their diastolic-BP90 mmHg following repeated examination or a patient receives antihypertensive-drugs
General obesity will be measured by determining of BMI kgm2 Abdominal obesity is assessed by waist circumference using the standards for the Asian nationality by IDF2018 56
Body composition parameters including fat mass visceral fat fat-free mass total body-water musclebone mass metabolic age basal-metabolic-rate and bioimpedance will be evaluated by Tanita-MC-980MA Multi-Frequency Segmental Body-Composition-AnalyzererTanitaCorpJapan
Physical activity will be assessed as the number of steps taken by patients as determined by individual pedometers from Hoffmann-La-RocheSwitzerland or other individual digital system
Laboratory study On the same blood samples standard laboratory a complete blood count erythrocyte sedimentation rate urea creatinine glucose electrolytes HbA1c lipid profile total-cholesterol HDLLDL triglycerides total proteins coagulation profile bilirubin hepatic enzyme activities blood urine ketone bodies
Hormones assay Fasting serum insulin by immunoassay method CzechRepublic The Homeostasis Model Assessment insulin resistance indexes HOMA-IR will be used as a surrogate measure of insulin sensitivity as follows HOMA-IRfasting insulin in nULfasting glucose in mmoll225
Measurement of TL TL will be measured in TS ratio with an adaptation of the quantitative polymerase chain reaction q-PCR methods The intraassay and interassay variability CV for quantitative polymerase chain reaction will be shown
Blood samples for measurement of TL will be collected in sterile vacutainer and delivered to the Genom and personalized medicine laboratory Nazarbayev University DNA was purified using Promega Wisard DNA system in -20 С In short for measurement of telomere repeat copies primers will be added Two control samples will be run in each experiment to allow for normalization between experiments and periodical reproducibility experiments will be performed to guarantee correct measurements The ratio calculated is proportional to average TL per cell
Quality of life assesses with international questionnaire BAROS Bariatric Analysis and Reporting Outcome System EuroQoL
Cost-effectiveness analysis conductes using as outcomes both clinical as well as EuroQol to estimate the incremental cost-effectiveness of the three alternative interventions Analysis considers specific costs a direct medical costs including the intervention itself and follow-up care to the condition b indirect nonmedical costs and c additional non-medical costs Costs of medical care obtaines from economic departments of participating medical centers identifying resources consumed during the interventions Indirect costs obtaines from patients The limited time horizon of this study will make it necessary to use a model to extrapolate the observed effect of the treatments assessed in the long term
Consultations of specialists conductes beforeduringafter the study 24-week period
Imaging methods Ultrasound of internal organs GE Vivid 7 Ultrasound GE Healthcare Worldwide USA Michigan ECG
Interpretation of the data The primary hypothesis is that patients treated with the comparative methods would experience a greater weight reduction and improving in the primarysecondary endpoints then the groups selects to compare between themselves in the aggregate using multiple linear regression analysis To establish the effectiveness of the comparative methods based on the principle H0 null hypothesis one method doesnt differ from anotherother and Ha alternative one method differs from anotherother
Statistical analysis The statistical analysis plan considers non-compliance loss-of-follow-up and missing-data Multiple-logistic-regression-models ANOVAANCOVA uses to predict the probability of specific variables Mixed-effect-models or generalized-estimating-equations GEE evaluates with statisticians The Students two-factor-t-test OR 95CI Pearsons criterion-χ2 will be used to assess differences in proportions Mann-Whitney U-test and Kruskal-Wallis test are used for nonparametric Pearson or Spearman correlation coefficient r To determine dependentindependent variables and to control confounders discusses between the team using literature data
Regression analysis performs using state of the art machine learning algorithms in python code These include application of algorithms such as KNN SVM and Random Forests Additionally the investigators will apply deep learning methodology for creating a model to test the hypothesis testing as a binary classifier This learning model uses neural network given new data will be able to make personalized effects of the three treatment methods Study data presentes in tables as MSE or median 25-75 based on distribution of variables Survival analysis Kaplan-Meier or Cox-regression uses to assess mortality in the three comparative treatments Statistical analysis using SPSS for Windowsver280
Ethics The appropriate national and institutional regulatory authorities and ethics committees will approve the study design and all participants will provide written informed consent The study will fulfilled in University Medical Center together with Nazarbayev University School of Medicine and National Laboratory Astana and Astana Medical University
Inclusion criteria 1 written informed consent 2 35 age 65 years old 2 any BMI and WC 3 diagnosis of T2D and hypertension 3 years and treatment with non-hormonal conventional pharmacological medications 4 any level of triglycerides cholesterol body fat 5 weight loss on the RF for 30 days
Exclusion criteria 1 age 35 or 65 years old 1 Insulin-depended T2D and uncontrolled high BP 2 patients taking gastrointestinal lipase inhibitors etc 3 presence of acute infection diseases or exacerbation of chronic diseases 4 ejection fraction 30 5 history of alcohol consumption 30 gday within the past 5 years 6 malignancy within the past 5 years gestation or lactation kidney failure hereditary diseases or known hypersensitivity to any of the test substances
Outcome measures Primary endpoints weight loss fasting blood glucose blood insulin level systolicdiastolic BP Secondary endpoints blood lipids heel bone mineral density HBMD and EF
Intervention The participants adhered to fasting on RF season They strictly adhered to two principles of nutrition during RF 1 no blood no smell of fat which means dont eat meat and dont eat fatty foods 2 the Sehri time a meal eaten before dawn included just 15-20 glass of water and fruits of 80-100 gr apple dates and persimmon Indeed the patients followed a diet in which they ate one meal a day - participants have a meal during Iftar time a meal eaten after sunset The participants also adhered to walking at least 3000 stepsday sexual self-restraint
A combination of in-person conversations and telephone calls conductes during the 30-day study period the baseline7-day14-day and 30-day RF
At the 2nd stage of the study will include totally 150 adult patients with MS distributed in three comparative groups drug treatment surgery and diet therapy
The study design is prospective because the investigators have to comparatively measure TL beforeafter interventions the study may not be an observation study Because of the trial will non-randomized patients will be allocated to each group based on equal baseline characteristics according to the inclusionexclusion criteria and including adjustments for baseline and confounding characteristics
The patients will be allocated to each group based on the patient and two physicians surgeon and therapist decisions to avoid the risk of selection bias Normalization of parameters will focuse on the work required to embed processes into statistics
Inclusion criteria 1 written informed consent 2 T2D3-year with glucose lowering therapy including insulin 3 35-55 years old 4 BMI27 kgm2 for both sex for Asian ethnicity 5 ongoing treatment with antihypertensive treatment 6 weight loss 15-20 at baseline and dynamic follow-up up to 24 weeks
All included patients before recruiting to the study received standard-of-care treatment for T2D and AH according to regional guidelines
Exclusion criteria T1D 34 age 56 years old unstable cardiac disorders New York Heart Association class IV heart failure refractory angina uncontrolled arrhythmias critical valvular heart disease or severe uncontrolled hypertension glomerular filtration rate 30 mLmin andor dialysis within 14 days before screening malignancy within the past 5 years gestation or lactation hereditary diseases known hypersensitivity to any of the test substances
The 1st group n50 receives subcutaneous Semaglutide GLP-1RA 1 mg once a 7 day with oral Empagliflozin SGLT-2i 25 mg once a day that is a novel combination additionally to standard medical treatment including anti-diabetes antihypertensive lipid-lowering symptomatic therapy
The 2nd group n50 receives surgical method laparoscopic MGB These patients pass through additional pre-operation examination blood tests and electrocardiography esophagogastroscopy ultrasound and other necessary standard methods
The 3rd group n50 receives very-low-calorie-restriction diet Analimentary-detoxication including 100 kcalday with fat-free vegetables tomatocucumber and salt intake 5-6 gday optimum physical activity and sexual self-restraint The program goals the next outputs a use of own fatty store b control endogen intoxication c reuse of interim metabolic substrates
A combination of in-person conversations and telephone calls conduct during the study period
Justification of the sample size The estimated treatment difference will set to 10 with a standard deviation of 8 and the superiority margin of 5 δ005 based on two-sided hypothesis testing Using SPSSSample-PowerV230 the number of evaluable individuals needed per treatment arm 32 At least 150 patients will be screened and recruited in the comparative clinical trial
End Points The primary endpoints reduction in body weight 15-20 from baseline leukocyte TL The secondary endpoints HbA1c fasting blood glucose and 2-hour oral glucose tolerance test OGTT systolicdiastolic BP lipid profile immunoassay insulin in blood adverse events
Methods
Criteria for the diagnosis of MS Diagnosis of MS IDF-2005 Diagnosis T2D HbA1c65 fasting plasma glucose level 70 mmoll or a patient receives antidiabetic therapy ADA 2023 55 AH systolic-BP130 andor their diastolic-BP90 mmHg following repeated examination or a patient receives antihypertensive-drugs
General obesity will be measured by determining of BMI kgm2 Abdominal obesity is assessed by waist circumference using the standards for the Asian nationality by IDF2018 56
Body composition parameters including fat mass visceral fat fat-free mass total body-water musclebone mass metabolic age basal-metabolic-rate and bioimpedance will be evaluated by Tanita-MC-980MA Multi-Frequency Segmental Body-Composition-AnalyzererTanitaCorpJapan
Physical activity will be assessed as the number of steps taken by patients as determined by individual pedometers from Hoffmann-La-RocheSwitzerland or other individual digital system
Laboratory study On the same blood samples standard laboratory a complete blood count erythrocyte sedimentation rate urea creatinine glucose electrolytes HbA1c lipid profile total-cholesterol HDLLDL triglycerides total proteins coagulation profile bilirubin hepatic enzyme activities blood urine ketone bodies
Hormones assay Fasting serum insulin by immunoassay method CzechRepublic The Homeostasis Model Assessment insulin resistance indexes HOMA-IR will be used as a surrogate measure of insulin sensitivity as follows HOMA-IRfasting insulin in nULfasting glucose in mmoll225
Measurement of TL TL will be measured in TS ratio with an adaptation of the quantitative polymerase chain reaction q-PCR methods The intraassay and interassay variability CV for quantitative polymerase chain reaction will be shown
Blood samples for measurement of TL will be collected in sterile vacutainer and delivered to the Genom and personalized medicine laboratory Nazarbayev University DNA was purified using Promega Wisard DNA system in -20 С In short for measurement of telomere repeat copies primers will be added Two control samples will be run in each experiment to allow for normalization between experiments and periodical reproducibility experiments will be performed to guarantee correct measurements The ratio calculated is proportional to average TL per cell
Quality of life assesses with international questionnaire BAROS Bariatric Analysis and Reporting Outcome System EuroQoL
Cost-effectiveness analysis conductes using as outcomes both clinical as well as EuroQol to estimate the incremental cost-effectiveness of the three alternative interventions Analysis considers specific costs a direct medical costs including the intervention itself and follow-up care to the condition b indirect nonmedical costs and c additional non-medical costs Costs of medical care obtaines from economic departments of participating medical centers identifying resources consumed during the interventions Indirect costs obtaines from patients The limited time horizon of this study will make it necessary to use a model to extrapolate the observed effect of the treatments assessed in the long term
Consultations of specialists conductes beforeduringafter the study 24-week period
Imaging methods Ultrasound of internal organs GE Vivid 7 Ultrasound GE Healthcare Worldwide USA Michigan ECG
Interpretation of the data The primary hypothesis is that patients treated with the comparative methods would experience a greater weight reduction and improving in the primarysecondary endpoints then the groups selects to compare between themselves in the aggregate using multiple linear regression analysis To establish the effectiveness of the comparative methods based on the principle H0 null hypothesis one method doesnt differ from anotherother and Ha alternative one method differs from anotherother
Statistical analysis The statistical analysis plan considers non-compliance loss-of-follow-up and missing-data Multiple-logistic-regression-models ANOVAANCOVA uses to predict the probability of specific variables Mixed-effect-models or generalized-estimating-equations GEE evaluates with statisticians The Students two-factor-t-test OR 95CI Pearsons criterion-χ2 will be used to assess differences in proportions Mann-Whitney U-test and Kruskal-Wallis test are used for nonparametric Pearson or Spearman correlation coefficient r To determine dependentindependent variables and to control confounders discusses between the team using literature data
Regression analysis performs using state of the art machine learning algorithms in python code These include application of algorithms such as KNN SVM and Random Forests Additionally the investigators will apply deep learning methodology for creating a model to test the hypothesis testing as a binary classifier This learning model uses neural network given new data will be able to make personalized effects of the three treatment methods Study data presentes in tables as MSE or median 25-75 based on distribution of variables Survival analysis Kaplan-Meier or Cox-regression uses to assess mortality in the three comparative treatments Statistical analysis using SPSS for Windowsver280
Ethics The appropriate national and institutional regulatory authorities and ethics committees will approve the study design and all participants will provide written informed consent The study will fulfilled in University Medical Center together with Nazarbayev University School of Medicine and National Laboratory Astana and Astana Medical University
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