Sleeve Procedure vs Liraglutide vs Empagliflozin in NASH Disease and Obesity RCT (SPLENDOR)

Phase 3

• Conditions: Condition 1: Nonalcoholic Steatohepatits (NASH). Condition 2: Obesity.; Nonalcoholic steatohepatitis (NASH); Overweight and obesity; K75.81

• Registration Number: IRCT20200128046294N1
• Lead Sponsor: Dr. Abidi Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 21 June 2021

Recruitment & Eligibility

• Status: Pending
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

Is a candidate for general anesthesia
Is eligible for bariatric surgery (SG)
Is =18 and =65 years old
Have a BMI =30 and =45 kg/m2
Have a platelet count >150,000 and International Normalized Ratio (INR) =1.2
Have appropriate composite entry criteria on liver biopsy: NAFLD with activity score between 4 and 8, presence of hepatocyte ballooning, and fibrosis stage between 1 and 3, confirmed by independent reviews by 3 liver pathologists. In case of any discrepancies in histopathologic report, a joint review by 3 study pathologists will be performed.
Have the ability and willingness to participate in the study and agree to any of the arms involved in the study.
Able to understand the options and to comply with the requirements of each arm.
Have a negative urine pregnancy test at screening and randomization visits for women of childbearing potential.
Women, of childbearing age, must agree to use reliable method of contraception for 1 year.
11.Patients with and without T2DM are eligible for the study. Patients with T2DM should have been on a stable dose of anti-diabetic medication for at least 3 months prior to entry, with HbA1c =8.5%.
ALT & AST > 35 in female and 45 in male

Exclusion Criteria

1.Known history of other chronic liver diseases (drug induced, viral hepatitis, autoimmune, and genetic): a.Hepatitis B as detected by presence of hepatitis B surface antigen (HBsAg), b.Hepatitis C as detected by presence of hepatitis C virus (HCV) RNA, c.Autoimmune liver disease as diagnosed by antibodies and compatible liver histology, d.Primary biliary cirrhosis as defined by the presence of at least 2 criteria (elevated alkaline phosphatase, presence of anti-mitochondrial antibody, and histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts), e.Primary sclerosing cholangitis, f.Wilson’s disease as diagnosed by low ceruloplasmin and compatible liver histology, g.Alpha-1-antitrypsin deficiency as diagnosed by alpha1-antitrypsin level and liver histology, h.Hemochromatosis as diagnosed by presence of 3+ or 4+ stainable iron on liver biopsy, i.Drug-induced liver disease as diagnosed by medical history, j.Known bile duct obstruction, k.Suspected or proven liver cancer
Type 1 diabetes or autoimmune diabetes
Known cases of human immunodeficiency virus infection
Prior bariatric surgery of any kind
Prior complex foregut surgery including any esophageal and gastric surgeries, anti-reflux procedures, splenectomy, biliary diversion, and trauma
Thoracic, abdominal, pelvic and/or obstetric-gynecologic surgery within 6 months
Any other surgery requiring general anesthesia within 6 weeks prior to signing the consent
American Society of Anesthesiologists Class IV or V
History of solid organ transplant
Severe pulmonary disease defined as FEV1 < 50% of predicted value
Cardiovascular conditions including significant known coronary artery disease, dysrhythmia, uncompensated congestive heart failure, history of stroke, or uncontrolled hypertension (defined as medically treated with the mean of 3 separate measurements systolic blood pressure > 180 mm Hg or diastolic blood pressure> 110 mm Hg)
Chronic renal insufficiency with a eGFR is below 45 mL/min/1.73 m2, or being on dialysis
Presence of moderate to severe GERD (Los Angeles classification B-D)
Presence of moderate to large hiatal hernia (>3 cm)
Presence of inflammatory bowel disease (Crohn’s disease or ulcerative colitis)
Psychiatric disorders including dementia, active psychosis, severe depression requiring > 2 medications, history of suicide attempts, active alcohol or substance abuse within the previous 12 months
Pregnancy
Breastfeeding
Diagnosis of malignancy within three years (except squamous cell and basal cell cancer of the skin)
Anemia defined as hemoglobin less than 9 g/dL
Any medical condition requiring anticoagulation therapy that cannot be temporarily discontinued for surgical procedure
Known history of clotting disorders, including pulmonary embolus and deep vein thrombosis
Use of any medications (prescription or over the counter), including herbal or other supplements for treatment of obesity or liver conditions (e.g. vitamin E or pioglitazone) during the last 3 months
Use of investigational therapy or participation in any other clinical trial within 3 months prior to signing the consent
History of pancreatitis (acute or chronic) or pancreatic carcinoma
History of thyroid cancer
Presence of concerning thyroid nodule
Family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
Liver biopsies < 5 mm in length
Absence of hepatocyte ballooning on liver biopsy
Absence of fibrosis on liver biopsy
NAFLD Activity

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
iver Histopathology. Timepoint: before intervention and 12 months after intervention. Method of measurement: NAFLD activity score + hepatocellular ballooning + Fibrosis stage.