Ignite Creation Date:
2024-05-06 @ 12:45 PM
Last Modification Date:
2024-10-26 @ 1:03 PM
Study NCT ID:
NCT03836937
Status:
COMPLETED
Last Update Posted:
2022-05-17
First Post:
2019-01-09
Brief Title:
Role of Obeticholic Acid in the Patients of NAFLD With Raised ALT
Sponsor:
Sir Salimullah Medical College Mitford Hospital
Organization:
Sir Salimullah Medical College Mitford Hospital
Study Overview
Official Title:
Role of Obeticholic Acid in the Patients of NAFLD With Raised ALT- A Randomized Clinical Control Trial Study
Status:
COMPLETED
Status Verified Date:
2022-05
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:
NAFLD
Brief Summary:
This study will be conducted upon the patients with fatty liver disease Patients who will be diagnosed as a case of fatty liver disease by ultrasound with raised liver enzyme ALT will be primarily selected for the study A total number of 70 patients will be randomly selected for the study that will also be divided into two groups for the study purpose The patients will be informed about the details of the study After getting the detail information those who will give informed written consent will be finally included in the study One group of patients will be treated by both life style modification and Obeticholic acid Another group of patients by only life style modification After 3 months of treatment the two groups will be compared of improvement of fatty liver disease and liver enzyme by improvement of fibroscan with CAP value as well as improvement of ALT value
Detailed Description:
Non-alcoholic fatty liver disease NAFLD is an increasingly common cause of chronic liver disease worldwide and it is associated with increased liver-related mortality and hepatocellular carcinoma even in the absence of cirrhosis The prevalence of NAFLD is steadily increasing and is currently 20-30 in Western countries and 5-18 in Asia It progresses to cirrhosis in 15-20 of affected individuals and is a rising indication for liver transplantation NAFLD is the commonest cause of elevated liver enzymes Lifestyle modifications including diet and exercise are imperative for achieving weight loss and reducing insulin resistance and hepatic steatosis and inflammation in patients with NAFLD But are suboptimal by long-term adherence in patients with NAFLD On the other hand current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile In this context obeticholic acid a selective agonist of the farnesoid X receptors might represent a useful option in these patients Preclinical studies suggest that obeticholic acid improves hepatic steatosis inflammation and fibrosis A randomized placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment FLINT trial also showed improvements in liver histology in patients with NAFLD who received obeticholic acid So there is a need to develop more effective and safe agents for this common and life-threatening disease
Farnesoid X receptor FXR is a member of the nuclear receptor super family expressed in the liver kidney intestine and adrenal glands In addition to regulation of bile acid BA synthesis several lines of evidence have suggested that FXR plays a role in the pathophysiology of NAFLDNASH Obeticholic acid is a synthetically modified bile acid that is a potent agonist of the farnesoid X nuclear receptor FXR a nuclear receptor with major effects on bile acid synthesis and transport as well as lipid metabolism and glucose homeostasis Obeticholic acid has been shown to improve serum enzymes in several diseases including nonalcoholic fatty liver disease and primary biliary cirrhosis In FLINT trial treatment with obeticholic acid 25 mgday for 72 weeks resulted in a highly statistically significant improvement in the NAFLD Activity Score of at least two points with no worsening of fibrosis 45 50 of 110 of the treated group had this improvement compared with 21 23 of 109 of the placebo-treated controls
The objective of the study will be to assess the efficacy of obeticholic acid on improvement of NAFLD and ALT values in patients with fatty liver disease
The study will be conducted in the department of Hepatology Sir Salimullah Medical College and Mitford Hospital It will be a randomized open label clinical control trial study Patients diagnosed with non-alcoholic fatty liver disease NAFLD will be initially targeted for the study Patients who will be diagnosed as a case of NAFLD by ultrasound with raised Alanin aminotransferase ALT 40 UL will be primarily selected for the study The total sample size will be 70 that will be divided into two groups Group-A and Group-B for the study purpose The patients will be informed about the details of the study After getting the detail information those who will give informed written consent will be finally included in the study A series of baseline investigations including CBC with ESR fasting blood sugar FBS 2 hours after 75 g glucose alanine aminotransferase ALT aspartate-aminotransferase AST gamma-glutamyl transpeptidase GGT bilirubin B PT with INR serum albumin total cholesterol TC triglycerides TG LDL-C HDL-C Thyroid function test will be determined on fresh serum using an auto-analyzer Fibroscan with CAP as well as ALT will be done to assess the baseline status of the patients at the time of enrollment of the study Group-A patients will be treated by both life style modification and Obeticholic acid and Group-B patients by only life style modification We shall give 10 mg obeticholic acid twice daily to the patients of Group-1 Life style modification including moderate exercise that is 30 minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar containing diet and intake of at least 3 vegetables per day will be advised to all the patients in both Groups The patients will be followed for 3 months Patients will come for follow-up after 1 month and finally after 3 months Each visit will take place between 1000 am to 0200 pm consist with a clinical examination blood pressure BP body mass index BMI determinations and a questionnaire BMI will be computed using the formula weight kg square of height meters Serum will be collected for CBC with ESR FBS 2 hours after 75 g glucose ALT AST PT with INR serum albumin GGT TC TG HDL LDL in first and last visit An alcohol consumption questionnaire will also be administered in each visit and study compliance will be strictly monitored After 3 months of treatment the two groups will be compared of improvement of NAFLD and liver enzyme by improvement of fibroscan with CAP value as well as improvement of ALT value with the baseline ALT and fibroscan with CAP values
All Data will be presented as mean SD analyzed by SPSS version 23 Qualitative data will be analyzed by Chi-square test quantitative data will be analyzed by students t-test A statistically significant result will be considered when P value 005
Farnesoid X receptor FXR is a member of the nuclear receptor super family expressed in the liver kidney intestine and adrenal glands In addition to regulation of bile acid BA synthesis several lines of evidence have suggested that FXR plays a role in the pathophysiology of NAFLDNASH Obeticholic acid is a synthetically modified bile acid that is a potent agonist of the farnesoid X nuclear receptor FXR a nuclear receptor with major effects on bile acid synthesis and transport as well as lipid metabolism and glucose homeostasis Obeticholic acid has been shown to improve serum enzymes in several diseases including nonalcoholic fatty liver disease and primary biliary cirrhosis In FLINT trial treatment with obeticholic acid 25 mgday for 72 weeks resulted in a highly statistically significant improvement in the NAFLD Activity Score of at least two points with no worsening of fibrosis 45 50 of 110 of the treated group had this improvement compared with 21 23 of 109 of the placebo-treated controls
The objective of the study will be to assess the efficacy of obeticholic acid on improvement of NAFLD and ALT values in patients with fatty liver disease
The study will be conducted in the department of Hepatology Sir Salimullah Medical College and Mitford Hospital It will be a randomized open label clinical control trial study Patients diagnosed with non-alcoholic fatty liver disease NAFLD will be initially targeted for the study Patients who will be diagnosed as a case of NAFLD by ultrasound with raised Alanin aminotransferase ALT 40 UL will be primarily selected for the study The total sample size will be 70 that will be divided into two groups Group-A and Group-B for the study purpose The patients will be informed about the details of the study After getting the detail information those who will give informed written consent will be finally included in the study A series of baseline investigations including CBC with ESR fasting blood sugar FBS 2 hours after 75 g glucose alanine aminotransferase ALT aspartate-aminotransferase AST gamma-glutamyl transpeptidase GGT bilirubin B PT with INR serum albumin total cholesterol TC triglycerides TG LDL-C HDL-C Thyroid function test will be determined on fresh serum using an auto-analyzer Fibroscan with CAP as well as ALT will be done to assess the baseline status of the patients at the time of enrollment of the study Group-A patients will be treated by both life style modification and Obeticholic acid and Group-B patients by only life style modification We shall give 10 mg obeticholic acid twice daily to the patients of Group-1 Life style modification including moderate exercise that is 30 minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar containing diet and intake of at least 3 vegetables per day will be advised to all the patients in both Groups The patients will be followed for 3 months Patients will come for follow-up after 1 month and finally after 3 months Each visit will take place between 1000 am to 0200 pm consist with a clinical examination blood pressure BP body mass index BMI determinations and a questionnaire BMI will be computed using the formula weight kg square of height meters Serum will be collected for CBC with ESR FBS 2 hours after 75 g glucose ALT AST PT with INR serum albumin GGT TC TG HDL LDL in first and last visit An alcohol consumption questionnaire will also be administered in each visit and study compliance will be strictly monitored After 3 months of treatment the two groups will be compared of improvement of NAFLD and liver enzyme by improvement of fibroscan with CAP value as well as improvement of ALT value with the baseline ALT and fibroscan with CAP values
All Data will be presented as mean SD analyzed by SPSS version 23 Qualitative data will be analyzed by Chi-square test quantitative data will be analyzed by students t-test A statistically significant result will be considered when P value 005
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