The primary objectives of this study are to evaluate the effect of ESG with OverStitch® system (Apollo Endosurgery, Austin, TX, USA) compared to LSG on 1) histological improvement in NASH; 2) all-cause mortality and liver-related outcomes In obese subjects with non-alcoholic steatohepatitis (NASH). Condition or disease: Non-alcoholic steatohepatitis (NASH) with or without fibrosis Intervention/treatment: ESG with OverStitch® system vs LSG
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Endoscopic technique defined as a gastric restriction by means of continuous sutures of the entire gastric wall of the antrum and body, transmurally, in order to simulate a gastric sleeve, in the same way as sleeve gastrectomy surgery. Gastroplasty is performed using an endoscopic suture system (OverStitch, Apollo Endosurgery Inc., Austin, Texas, USA) inserted into a dual-channel endoscope (GIF-2T160, Olympus Medical Systems Corp., Tokyo, Japan).
Minimally invasive surgical technique defined as a gastric restriction by means of an excision approximately 80% of the stomach along the greater curvature.
Hospitl Universitario Marqués de Valdecilla
Santander, Cantabria, Spain
RECRUITINGProportion of subjects undergoing ESG relative to LSG achieving resolution of NASH without worsening of fibrosis
To evaluate the effect of ESG compared to LSG on liver histology in obese subjects with NASH with or without fibrosis by assessing the following endpoint: The proportion of subjects undergoing ESG relative to LSG achieving NASH resolution without worsening of fibrosis. NASH resolution is defined as the disappearance of ballooning and the disappearance or persistence of minimal lobular inflammation (grade 0 or 1) The worsening of fibrosis is defined as the progression of at least one stage.
Time frame: Measurement at 96 weeks
Proportion of subjects undergoing ESG relative to LSG with cardiovascular and liver-related death events
To evaluate the effect of ESG compared to LSG on liver histology in obese subjects with NASH with fibrosis by assessing the following endpoint: The proportion of subjects undergoing ESG relative to LSG achieving improvement of liver fibrosis of at least one stage.
Time frame: Measurement at 96 weeks
Proportion of subjects undergoing ESG relative to LSG achieving improvement in liver histology according to the NASH-CRN scoring
Percentage of patients with at least 1 point improvement
Time frame: Measurement at 96 weeks
Changes in the liver enzymes
ALT, AST, GGT, AP (U/L)
Time frame: Measurement at 96 weeks
Changes in lipid parameter
Cholesterol, LDL, HDL, Triglycerides (mg/dL)
Time frame: Measurement at 96 weeks
Changes in noninvasive markers of fibrosis and steatosis
Fatty Liver Index (FLI) (\<30; 30-60; \>60)
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Time frame: Measurement at 96 weeks
Changes in noninvasive markers of fibrosis and steatosis
Hepatic steatosis index (HSI) (\<30; 30-36; \>36)
Time frame: Measurement at 96 weeks
Changes in noninvasive markers of fibrosis and steatosis
NAFLD fibrosis score (NFS) (\<-1.455; -1.455-0.676; \>0.676)
Time frame: Measurement at 96 weeks
Changes in noninvasive markers of fibrosis and steatosis
AST to Plateler ratio index (APRI) (\<1, \>1)
Time frame: Measurement at 96 weeks
Changes in noninvasive markers of fibrosis and steatosis
Fibrosis-4 (FIB-4) (\<1.30; 1.30-2.67; \>2.67)
Time frame: Measurement at 96 weeks
Changes in noninvasive markers of fibrosis and steatosis
Hepamet fibrosis score (HFS) (\<0.12; 0.12-0.47; \>0.47)
Time frame: Measurement at 96 weeks
Changes in body weight
body weight
Time frame: Measurement at 96 weeks
Changes in inflammatory markers
Ferritin in ng/mL
Time frame: Measurement at 96 weeks
Changes in inflammatory markers
C-rective protein (CRP) in mg/dL
Time frame: Measurement at 96 weeks
Changes in inflammatory markers
High sensitivity C-reactive protein (hs-CRP) in mg/L
Time frame: Measurement at 96 weeks
Changes in inflammatory markers
Interleukin 6 (IL-6) in pg/mL
Time frame: Measurement at 96 weeks
Changes in inflammatory markers
Interleukin 1 beta (IL-1b) in pg/mL
Time frame: Measurement at 96 weeks
Changes in inflammatory markers
Tumor necrosis factor alpha (TNFa) in pg/mL
Time frame: Measurement at 96 weeks
Changes in serum expression of incretins
serum expression of incretins
Time frame: Measurement at 96 weeks
Changes in mineral metabolism parameters.
Parathormone (PTH) (pg/mL), 25(OH)D (ng/mL), PINP, b-CTX (ng/mL)
Time frame: Measurement at 96 weeks
Changes in gut microbiota
Analysis using 16S rRNA sequencing from stool samples
Time frame: Measurement at 96 weeks
Changes in glucose homeostasis markers and insulin resistance
Glucose in mg/dL
Time frame: Measurement at 96 weeks
Changes in glucose homeostasis markers and insulin resistance
Hemoglobin A1c (HbA1c) in %
Time frame: Measurement at 96 weeks
Changes in glucose homeostasis markers and insulin resistance
Homeostatic model assessment for insulin resistance (HOMA-IR) (not unit)
Time frame: Measurement at 96 weeks
Changes in glucose homeostasis markers and insulin resistance
Adponectin in ug/mL
Time frame: Measurement at 96 weeks
Changes in glucose homeostasis markers and insulin resistance
Retinol binding protein 4 (RBP-4) in ug/mL
Time frame: Measurement at 96 weeks
Changes in glucose homeostasis markers and insulin resistance
Monocyte chemoattractant protein-1 (MCP-1) in ug/mL
Time frame: Measurement at 96 weeks
Changes in glucose homeostasis markers and insulin resistance
Plaminogen activator inhibitor-1 (PAI-1) in ug/mL
Time frame: Measurement at 96 weeks
Incidence of adverse events
Safety and tolerability
Time frame: Measurement at 96 weeks