Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06364930
Status:
RECRUITING
Last Update Posted:
2024-04-15
First Post:
2024-04-08
Brief Title:
SGLT2i to Prevent of Liver Complications in Patients With CHB and Diabetes Mellitus
Sponsor:
Chinese University of Hong Kong
Organization:
Chinese University of Hong Kong
Study Overview
Official Title:
Sodium-glucose Co-transporter-2 Inhibitor SGLT2i to Prevent of Liver Complications in Patients With Chronic Hepatitis B and Diabetes Mellitus a Double-blind Randomised Placebo-controlled Trial
Status:
RECRUITING
Status Verified Date:
2024-08
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:
This is a five-year double blinded randomised trial of dapagliflozin versus placebo in patients with chronic hepatitis B and DM or IFG complicated with compensated advanced chronic liver disease cACLD 412 subjects will be recruited Subject will be randomly assigned to receive dapagliflozin 10mg daily or dapagliflozin placebo one tablet daily for up to 5 years After randomization subject will be followed up at month 3 month 6 and then 6-monthly until 60 months follow up 4 weeks from scheduled clinic visit is allowed At each visit drug compliance physical examination observed or reported adverse events will be assessed 10ml of blood will be taken at each visit and transient elastography to assess fibrosis regression will be performed at 60th month or at withdrawal visit You are discouraged to use pegylated-interferon any other NA including lamivudine adefovir and telbivudine another SGLT2i Empagliflozin Jardiance Dapagliflozin Metformin XR Xigduo
Detailed Description:
Chronic hepatitis B virus HBV infection is a global health problem affecting approximately 234 million people worldwide of those three-quarter come from the Asia-Pacific region1 Up to 30-40 of chronically infected persons will die of liver complications including liver cancer and cirrhotic complications2 The Global Burden of Disease Study 2016 revealed HBV as one of the top ten killers worldwide3 Chronic HBV infection also represents a major global economic burden with increasing socioeconomic costs4 Majority of the liver complications and deaths is related to hepatocellular carcinoma HCC because of its high incidence rate and unfavourable clinical course5
Sodium-glucose co-transporter-2 inhibitors SGLT2i is a potent antidiabetic agent that lowers blood glucose by inducing renal glycosuria15 SGLT2i reduces cardiovascular and renal events by marked cardiac anti-fibrotic and anti-inflammatory effects16 on top of dramatic weight reduction6 A recent open-label pilot study of nine patients with biopsy-proven non-alcoholic steatohepatitis NASH with type 2 DM received a SGLT2i empagliflozin 25 mg daily for 24 weeks SGLT2i led to histological improvement in steatosis ballooning and fibrosis compared with historical placebo7 SGLT2i also leads to more significant reduction of ALT8 Several other randomised trials and cohort studies supported that SGLT2i also reduces liver fat content and liver fibrosis scores SGLT2i has additional benefits on liver histology compared to other antidiabetic agents8 The key pathways include control of hepatic inflammation and fibrosis improvement of insulin resistance and reduction of hepatic steatosis The related mechanisms involve inflammatory parameters like high-sensitivity C-reactive protein proinflammatory cytokines like interleukin-6 or TNF-alpha reactive oxygen species and the inhibition of AMPc activation The improvement was correlated with reductions in body weight waist circumference and inflammatory parameters The improvement was not correlated with changes in glucose control9 All these favourable effects on liver have make it potentially useful to reduce liver complications
Chronic hepatitis B is major cause of liver complications and death Antiviral treatment with oral nucleostide analogues reduces but not abolish the risk of liver complications especially in those with diabetes mellitus Sodium-glucose co-transporter-2 inhibitors SGLT2i are promising in improving liver outcome in patients with chronic hepatitis B and diabetes mellitus Our preliminary data provide strong plausibility that SGLT2i reduces the risk of liver complications We are going to provide the definitive answer to this important clinical question through a randomised trial
Sodium-glucose co-transporter-2 inhibitors SGLT2i is a potent antidiabetic agent that lowers blood glucose by inducing renal glycosuria15 SGLT2i reduces cardiovascular and renal events by marked cardiac anti-fibrotic and anti-inflammatory effects16 on top of dramatic weight reduction6 A recent open-label pilot study of nine patients with biopsy-proven non-alcoholic steatohepatitis NASH with type 2 DM received a SGLT2i empagliflozin 25 mg daily for 24 weeks SGLT2i led to histological improvement in steatosis ballooning and fibrosis compared with historical placebo7 SGLT2i also leads to more significant reduction of ALT8 Several other randomised trials and cohort studies supported that SGLT2i also reduces liver fat content and liver fibrosis scores SGLT2i has additional benefits on liver histology compared to other antidiabetic agents8 The key pathways include control of hepatic inflammation and fibrosis improvement of insulin resistance and reduction of hepatic steatosis The related mechanisms involve inflammatory parameters like high-sensitivity C-reactive protein proinflammatory cytokines like interleukin-6 or TNF-alpha reactive oxygen species and the inhibition of AMPc activation The improvement was correlated with reductions in body weight waist circumference and inflammatory parameters The improvement was not correlated with changes in glucose control9 All these favourable effects on liver have make it potentially useful to reduce liver complications
Chronic hepatitis B is major cause of liver complications and death Antiviral treatment with oral nucleostide analogues reduces but not abolish the risk of liver complications especially in those with diabetes mellitus Sodium-glucose co-transporter-2 inhibitors SGLT2i are promising in improving liver outcome in patients with chronic hepatitis B and diabetes mellitus Our preliminary data provide strong plausibility that SGLT2i reduces the risk of liver complications We are going to provide the definitive answer to this important clinical question through a randomised trial
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