Ignite Creation Date:
2024-05-06 @ 8:20 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06348706
Status:
COMPLETED
Last Update Posted:
2024-04-05
First Post:
2024-03-25
Brief Title:
Effect of Dipeptidyl Peptidase- 4 Inhibitors on Non-Alcoholic Steatohepatitis and Type 1 Diabetes
Sponsor:
Ain Shams University
Organization:
Ain Shams University
Study Overview
Official Title:
Effect of Dipeptidyl Peptidase- 4 Inhibitors Supplementation on Non-Alcoholic Steatohepatitis in Adolescents With Type 1 Diabetes Mellitus
Status:
COMPLETED
Status Verified Date:
2024-03
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 Non-alcoholic steatohepatitis NASH is an advanced form of non-alcoholic fatty liver disease NAFLD that can precipitate to advanced fibrosis and leads to cardiovascular morbidity and mortality Many patients with type 1 diabetes mellitus T1DM had histological evidence of steatosis and met the histological criteria for NASH Matrix metalloproteinase-14 MMP-14 is a type 1 transmembrane proteinase expressed in liver fibrosis and is involved in the development of atherosclerosis and cardiovascular disease Hepatic dipeptidyl peptidase-4 DPP-4 expression in NAFLD may be directly associated with hepatic lipogenesis and liver injury Some studies showed the beneficial effect of dipeptidyl peptidase-4 DDP-4 inhibitors in NAFLDNASH for their role in improving hepatic glucose metabolism Vildagliptin a DPP-4 inhibitor could be promising therapeutic agents for NAFLDNASH
To the best of our knowledge no previous study assessed the role of DPP-4 inhibitors in adolescent patients with T1DM and NASH
Objectives This randomized-controlled clinical trial assessed the impact of the oral DPP-4 inhibitor vildagliptin as an add-on therapy on NASH in adolescents with T1DM as well as its effect on glycemic control lipid profile MMP-14 levels and CIMT as a marker for subclinical atherosclerosis
Methods This study included 60 adolescents with T1DM and NASH with a mean age 156 208 years and disease duration 5 years Forty age- and sex-matched healthy subjects with a mean age 149 32 years were enrolled as healthy controls to compare MMP-14 levels T1DM patients were randomly assigned to receive oral vildagliptin 50 mg daily with lunch meal for six months or not Fasting and 2 hours post-prandial blood glucose levels HbA1c liver function tests fasting lipid profile hepatic steatosis index and triglyceride glucose TyG index were assessed MMP-14 levels were measured by enzyme-linked immunosorbent assay among all patients and healthy controls CIMT was assessed using Doppler ultrasound and transient elastography with controlled attenuation parameter CAP was performed to assess liver stiffness and steatosis stage
To the best of our knowledge no previous study assessed the role of DPP-4 inhibitors in adolescent patients with T1DM and NASH
Objectives This randomized-controlled clinical trial assessed the impact of the oral DPP-4 inhibitor vildagliptin as an add-on therapy on NASH in adolescents with T1DM as well as its effect on glycemic control lipid profile MMP-14 levels and CIMT as a marker for subclinical atherosclerosis
Methods This study included 60 adolescents with T1DM and NASH with a mean age 156 208 years and disease duration 5 years Forty age- and sex-matched healthy subjects with a mean age 149 32 years were enrolled as healthy controls to compare MMP-14 levels T1DM patients were randomly assigned to receive oral vildagliptin 50 mg daily with lunch meal for six months or not Fasting and 2 hours post-prandial blood glucose levels HbA1c liver function tests fasting lipid profile hepatic steatosis index and triglyceride glucose TyG index were assessed MMP-14 levels were measured by enzyme-linked immunosorbent assay among all patients and healthy controls CIMT was assessed using Doppler ultrasound and transient elastography with controlled attenuation parameter CAP was performed to assess liver stiffness and steatosis stage
Detailed Description:
Non-Alcoholic Fatty Liver Disease NAFLD is characterised by excessive hepatic fat accumulation steatosis in the absence of significant alcohol consumption occurring with or without hepatic inflammation and fibrosis Steatosis may progress to a more advanced form of the disease non-alcoholic steatohepatitis NASH which can precipitate to advanced fibrosis leading to cirrhosis andor hepatocellular carcinoma HCC and can result in the need for liver transplantation or death as well as cardiovascular morbidity and mortality
It was demonstrated that 531 of patients with type 1 diabetes mellitus T1DM had histological evidence of steatosis and 204 met the histological criteria for NASH Patients with T1DM onset at an earlier age have an increased incidence of cardiovascular disease CVD events and increased CVD mortality
Matrix metalloproteinases MMPs are found to have multiple biological activities including diseases like angiogenesis and cirrhosis They are expressed in atherosclerotic plaques promoting vascular remodelling contributing to atherothrombosis and plaque disruption MMP-14 is involved in the development of atherosclerosis and CVD MMP-14 is also noticed to be expressed in highly invasive hepatocellular carcinoma and expressed in liver fibrosis
Carotid ultrasound is easily available a cost effective and non-invasive tool for evaluating carotid artery intima-media thickness CIMT to assess CVD as carotid atherosclerosis CIMT was higher for individuals with NASH than for those with simple steatosis
Dipeptidyl peptidase-4 DPP-4 inhibitors are a relatively new class of oral diabetes drugs with a glucose-lowering effect DPP-4 inhibitors exert their glucose-lowering effects primarily by blocking the enzyme DPP-4 which is involved in the degradation of incretins including glucagon-like peptide-1 GLP-1 and glucose-dependent insulinotropic polypeptide GIP DPP-4 inhibitors are widely used for the treatment of type 2 diabetes since 2006 Although DPP-4 inhibitors may be beneficial for T1DM existing studies do not strongly support these positive effects in clinical practice
Vildagliptin an oral antihyperglycemic agent that competitively inhibits DPP-4 A few trials have demonstrated that vildagliptin has an effect on NAFLD In 44 patients with T2DM and hepatic steatosis vildagliptin treatment for 6 months decreased liver enzymes and intrahepatic triglyceride content as assessed by MRI In a study conducted in Pakistan vildagliptin for 12 weeks improved liver enzymes and steatosis grading as assessed by ultrasound
Aim To assess the effect of Dipeptidyl peptidase-4 DPP-4 inhibitors supplementation as an add on therapy on NASH in adolescents with type 1 diabetes mellitus as well as its effect on glycemic control lipid profile MMP-14 levels and CIMT as a marker for subclinical atherosclerosis
It was demonstrated that 531 of patients with type 1 diabetes mellitus T1DM had histological evidence of steatosis and 204 met the histological criteria for NASH Patients with T1DM onset at an earlier age have an increased incidence of cardiovascular disease CVD events and increased CVD mortality
Matrix metalloproteinases MMPs are found to have multiple biological activities including diseases like angiogenesis and cirrhosis They are expressed in atherosclerotic plaques promoting vascular remodelling contributing to atherothrombosis and plaque disruption MMP-14 is involved in the development of atherosclerosis and CVD MMP-14 is also noticed to be expressed in highly invasive hepatocellular carcinoma and expressed in liver fibrosis
Carotid ultrasound is easily available a cost effective and non-invasive tool for evaluating carotid artery intima-media thickness CIMT to assess CVD as carotid atherosclerosis CIMT was higher for individuals with NASH than for those with simple steatosis
Dipeptidyl peptidase-4 DPP-4 inhibitors are a relatively new class of oral diabetes drugs with a glucose-lowering effect DPP-4 inhibitors exert their glucose-lowering effects primarily by blocking the enzyme DPP-4 which is involved in the degradation of incretins including glucagon-like peptide-1 GLP-1 and glucose-dependent insulinotropic polypeptide GIP DPP-4 inhibitors are widely used for the treatment of type 2 diabetes since 2006 Although DPP-4 inhibitors may be beneficial for T1DM existing studies do not strongly support these positive effects in clinical practice
Vildagliptin an oral antihyperglycemic agent that competitively inhibits DPP-4 A few trials have demonstrated that vildagliptin has an effect on NAFLD In 44 patients with T2DM and hepatic steatosis vildagliptin treatment for 6 months decreased liver enzymes and intrahepatic triglyceride content as assessed by MRI In a study conducted in Pakistan vildagliptin for 12 weeks improved liver enzymes and steatosis grading as assessed by ultrasound
Aim To assess the effect of Dipeptidyl peptidase-4 DPP-4 inhibitors supplementation as an add on therapy on NASH in adolescents with type 1 diabetes mellitus as well as its effect on glycemic control lipid profile MMP-14 levels and CIMT as a marker for subclinical atherosclerosis
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?:
False
Is an FDA AA801 Violation?:
None