Effect of Bempedoic Acid on Liver Fat in Individuals With Nonalcoholic Fatty Liver Disease and Type 2 Diabetes: Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- The change in liver fat content
研究概览
简要总结
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions ranging from liver steatosis (NAFL), steatohepatitis (NASH), advanced liver fibrosis and ultimately leads to cirrhosis in a significant proportion of individuals. NAFLD is intimately associated with insulin resistance and associated disorders, such as type 2 diabetes, metabolic syndrome and dyslipidemia.
Bempedoic acid, an ATP-citrate lyase inhibitor, is recently approved for patients with dyslipidemia as a second line drug. Bempedoic acid reduces liver fat in mice model of NASH. Data regarding the effect of bempedoic acid on human liver fat are scarce. Therefore, the current study is planned to evaluate the effect of bempedoic acid versus standard treatment on liver and pancreatic fat content in patients with NAFLD
详细描述
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions ranging from liver steatosis (NAFL), steatohepatitis (NASH), advanced liver fibrosis and ultimately leads to cirrhosis in a significant proportion of individuals. NAFLD is intimately associated with insulin resistance and associated disorders, such as type 2 diabetes, metabolic syndrome and dyslipidemia.
Bempedoic acid, an ATP-citrate lyase inhibitor, is recently approved for patients with dyslipidemia as a second line drug. Bempedoic acid reduces liver fat in mice model of NASH. Data regarding the effect of bempedoic acid on human liver fat are scarce. Therefore, the current study is planned to evaluate the effect of bempedoic acid versus standard treatment on liver and pancreatic fat content in patients with NAFLD.
Materials and methods
Study design This B-LIFT (effect of Bempedoic acid on Liver fat content) trial is an investigator initiated, open label, randomized clinical study to examine the effect of bempedoic acid 180 mg tablet once a day for 24 weeks (Bemp group) versus standard treatment (control group) on liver and pancreatic fat content. Hepatic steatosis (intracellular fat accumulation in hepatocytes) will be measured by MRI-PDFF, a validated quantitative biomarker for liver fat. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) will be measured by Fibroscan. The study will be conducted according to the CONSORT guidelines. The patient population for the trial will be derived from Medanta-The Medicity Hospital endocrine out-patient clinic, who would primarily visit for management of type 2 diabetes and other co-morbidities. The study will be conducted in Medanta-The Medicity Hospital, Gurugram, Haryana, which is a tertiary care center in North India. Patients deemed eligible will be screened for the trial. The study will be registered at clinicaltrials.gov. The clinical trial protocol will be presented for approval to the institutional ethics review board. Informed written consent will be obtained from all the participants before enrolment into the study.
All patients will undergo a baseline assessment before randomization, including detailed medical history, physical examination including anthropometry and biochemical evaluation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A man or woman, 20 years of age or above with the diagnosis of type 2 diabetes for at least 3 months who meets all the following two criteria:
- •On standard anti-diabetic agents (metformin, DPP-4 inhibitors, sulphonylureas or insulin, in any combination) with an HbA1c of <9% at screening
- •Have documented hepatic steatosis (MRI-PDFF >5.6%) on screening MRI- PDFF
- •Participants must be medically stable based on medical history, physical examination and laboratory investigations.
- •Participants must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
- •Each participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of the study and are willing to participate in the study.
排除标准
- •History of diabetic ketoacidosis, type 1 diabetes, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy.
- •History of brittle or labile glycemic control, with widely varying glucose measurements by FPG or SMBG such that stable glucose control over the treatment period would be unlikely.
- •History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 3 years before Screening, or an Alcohol Use Disorders Identification Test (AUDIT) with a score >8, or alcohol consumption of more than 20 g per day in the case of women and more than 30 g per day in the case of men for at least three consecutive months during the previous 5 years.
- •Thyroid stimulating hormone (TSH) value that is either < 0.45 mIU/L or >10 mIU/L at Screening. Note: Subjects on thyroid hormone replacement therapy must be on a stable dose and dosing regimen for at least 4 weeks prior to enrollment.
- •Use of a PPAR-γ agonist [e.g., a thiazolidinedione (pioglitazone], an SGLT2 inhibitor (e.g., canagliflozin, empagliflozin, dapagliflozin), GLP-1 receptor agonists (e.g., liraglutide, dulaglutide) or saroglitazar (Dual PPARα/γ agonist) within 12 weeks before the enrollment.
- •BMI >40 kg/m
- •Ongoing eating disorder, or a significant weight loss or weight gain within 12 weeks before the Screening visit, defined as an increase or decrease of 5% in body weight based upon clinic-based measurement or, if not available, based on subject's report.
- •Use of weight loss medication (prescription and/or over the counter) within 3 months prior to Screening or have participated in a weight loss/diet program within 12 months prior to Screening.
- •Renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant.
- •Myocardial infarction, unstable angina, pulmonary hypertension, revascularization procedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 3 months before Screening, or revascularization procedure is planned, or subject has a history of New York Heart Association (NYHA) Class III-IV cardiac disease.
- •History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti- HCV at Screening.
- •Use of vitamin E within 12 weeks before screening.
- •History of prior bariatric (e.g., Roux-en-Y gastric bypass) or other major upper gastrointestinal surgical procedure (including gastric resection).
- •History of diabetic gastroparesis (or symptoms suggestive of this disorder, including postprandial bloating or vomiting), malabsorption, inflammatory bowel disease, or any other chronic, clinically important gastrointestinal disorder.
- •Estimated glomerular filtration rate (eGFR) <60 mL/min/1•73 m2 using the Modification of Diet in Renal Disease Study (MDRD) equation.
- •Subjects with a history of having or possibly having metallic material in the body or any contraindication for a MR examination.
- •Claustrophobia, or anxiety related to previous negative experiences with magnetic resonance imaging procedures or if the subject is unwilling to participate in magnetic resonance imaging procedures.
- •Clinically important hematologic disorder (e.g., symptomatic anemia, proliferative bone marrow disorder, thrombocytopenia) at Screening.
- •History of human immunodeficiency virus (HIV) antibody positive at Screening.
- •Major surgery (e.g., requiring general anesthesia) within 12 weeks before Screening, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study.
- •Contraindications to the use of bempedoic acid (per BEMPEDOIC ACID Prescribing Information).
- •Current use of a corticosteroid medication or immunosuppressive agent, or likely to require treatment with a corticosteroid medication or an immunosuppressive agent.
研究组 & 干预措施
Bem group
Patient will get Bempedoic acid along with the standard of Care
干预措施: Bempedoic acid (Drug)
结局指标
主要结局
The change in liver fat content
时间窗: Baseline to 24 Weeks
The primary outcome measure will be the difference of the change in liver fat content from 0 (baseline) to 24 weeks between groups
次要结局
- The change in controlled attenuation parameter(Baseline to 24 Weeks)
- Change between groups in gamma-glutamyl transpeptidase (GGT) levels.(Baseline to 24 Weeks)
- Change between the groups in total cholesterol levels.(Baseline to 24 Weeks)
- Change between groups in HDL levels(Baseline to 24 Weeks)
- Change between groups in alanine aminotransferase (ALT) levels(Baseline to 24 Weeks)
- Change between the groups in serum creatinine concentrations.(Baseline to 24 Weeks)
- The change in pancreatic fat(Baseline to 24 Weeks)
- Change between groups in triglycerides levels.(Baseline to 24 Weeks)
- The change in liver stiffness measurement (LSM)(Baseline to 24 Weeks)
- Change between the groups in aspartate aminotransferase (AST) levels(Baseline to 24 Weeks)
- Change between groups in LDL levels(Baseline to 24 Weeks)
研究者
Dr Mohammad Shafi Kuchay
Senior Consultant, Division of Endocrinology & Diabetes
Medanta, The Medicity, India