Efficacy and Safety of Endoscopic Sleeve Gastroplasty Versus Laparoscopic Sleeve Gastrectomy in Obese Subjects With NASH

Not Applicable

• Conditions: Non-alcoholic Steatohepatitis (NASH)
• Interventions: Procedure: Endoscopic Sleeve Gastroplasty (ESG) with OverStitch® system + Lifestyle modifications; Procedure: Laparoscopic Sleeve Gastrectomy (LSG) + Lifestyle modifications

• Registration Number: NCT04060368
• Lead Sponsor: Instituto de Investigación Marqués de Valdecilla

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-07-18
• Study First Submitted QC: 2019-08-14
• Study First Posted: 2019-08-19
• Study Start: 2020-06-01
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-28
• Last Update Posted: 2020-09-30
• Primary Completion: 2022-06-01
• Study Completion: 2023-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Subjects aged between 18 and 60 years (inclusive) at first screening visit.

2. Must provide signed written informed consent and agree to comply with the study protocol.

3. BMI between 35 and 45 kg/m2 with or without metabolic risk factors (type 2 diabetes, arterial hypertension, dyslipidaemia), and BMI between 30 and 34,9 kg/m2 with type 2 diabetes.

4. Histological confirmation of steatohepatitis in a diagnostic liver biopsy (biopsy obtained in the 6 months prior to randomization or during the selection period) with at least a score of 1 in each component of the NAS score (steatosis with a score of 0 to 3, degeneration by ballooning with a score of 0 to 2 and lobular inflammation with a score of 0 to 3) and:

   • NAS score ≥ 4
   • fibrosis < 4 according to the staging system of CRN fibrosis on NASH

5. For patients with fibrosis ≤ 1, must be associated at least one of the following conditions: metabolic syndrome (NCEP ATP III definition), type 2 diabetes, HOMA-IR >6

6. Absence of other well documented causes of chronic liver disease (alcoholic liver disease, viral hepatitis, cholestasis, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha 1 antitrypsin deficiency)

7. Patients agree to have 1 liver biopsy after 96 weeks after intervention

Exclusion Criteria

1. Known heart failure (Grade I to IV of the classification of the New York Heart Association).

2. History of efficient bariatric surgery within 10 years prior to Screening.

3. Patients with a history of clinically significant acute cardiac event in the 6 months prior to selection, such as: acute cardiovascular event, cerebrovascular accident, transient ischemic attack, or coronary heart disease (angina pectoris, myocardial infarction, revascularization procedures).

4. Weight loss of more than 5% in the 6 months prior to randomization.

5. Recent or current background of significant consumption of alcoholic beverages (<5 years). In the case of men, significant consumption is usually defined as more than 30 g of pure alcohol per day. In the case of women, it is usually defined as more than 20 g of pure alcohol per day.

6. Liver cirrhosis.

7. Non-cirrhotic portal hypertension.

8. Esophagogastric varices.

9. Hepatocellular carcinoma

10. Portal thrombosis.

11. Pregnancy.

12. Refusal to give informed consent.

13. Any medical condition that could reduce life expectancy to less than 2 years, including known cancers.

14. Signs of any other unstable or clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric disease without treatment.

15. Instability or mental incompetence, so that the validity of the informed consent or the ability to comply with the study are uncertain.

16. Antibodies positive for the human immunodeficiency virus.

17. Descompensated liver disease with the following hematologic and biochemical criteria:

    • Aspartate aminotransferase (AST) and / or ALT> 10 x upper limit of normal (ULN)
    • Total bilirubin> 25 μmol / l (1.5 mg / dl)
    • Standardized international index> 1.4
    • Platelet count <100 000 / mm3

18. Serum creatinine levels> 135 μmol / l (> 1.53 mg / dl) in men and> 110 μmol / l (> 1.24 mg / dl) in women.

19. Significant renal disease, including nephritic syndrome, chronic kidney disease (patients with markers of hepatic injury or estimated glomerular filtration rate [eGFR] of less than 60 ml / min / 1.73 m2). If an abnormal value is obtained at the first screening visit, the eGFR measurement may be repeated before randomization within the following time frame: minimum 4 weeks after the initial test and maximum 2 weeks before the expected randomization. An abnormal repeated eGFR (less than 60 ml / min / 1.73 m2) leads to exclusion from the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ESG Stitch® system + Lifestyle modifications	Endoscopic Sleeve Gastroplasty (ESG) with OverStitch® system + Lifestyle modifications	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).
LSG + Lifestyle modifications	Laparoscopic Sleeve Gastrectomy (LSG) + Lifestyle modifications	Minimally invasive surgical technique defined as a gastric restriction by means of an excision approximately 80% of the stomach along the greater curvature.

Primary Outcome Measures

Name	Time	Method
Proportion of subjects undergoing ESG relative to LSG achieving resolution of NASH without worsening of fibrosis	Measurement at 96 weeks	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.
Proportion of subjects undergoing ESG relative to LSG with cardiovascular and liver-related death events	Measurement at 96 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Changes in inflammatory markers	Measurement at 96 weeks	Tumor necrosis factor alpha (TNFa) in pg/mL
Proportion of subjects undergoing ESG relative to LSG achieving improvement in liver histology according to the NASH-CRN scoring	Measurement at 96 weeks	Percentage of patients with at least 1 point improvement
Changes in the liver enzymes	Measurement at 96 weeks	ALT, AST, GGT, AP (U/L)
Changes in body weight	Measurement at 96 weeks	body weight
Changes in serum expression of incretins	Measurement at 96 weeks	serum expression of incretins
Changes in glucose homeostasis markers and insulin resistance	Measurement at 96 weeks	Plaminogen activator inhibitor-1 (PAI-1) in ug/mL
Changes in lipid parameter	Measurement at 96 weeks	Cholesterol, LDL, HDL, Triglycerides (mg/dL)
Changes in noninvasive markers of fibrosis and steatosis	Measurement at 96 weeks	Hepamet fibrosis score (HFS) (\<0.12; 0.12-0.47; \>0.47)
Changes in mineral metabolism parameters.	Measurement at 96 weeks	Parathormone (PTH) (pg/mL), 25(OH)D (ng/mL), PINP, b-CTX (ng/mL)
Changes in gut microbiota	Measurement at 96 weeks	Analysis using 16S rRNA sequencing from stool samples
Incidence of adverse events	Measurement at 96 weeks	Safety and tolerability

Trial Locations

Locations (1)

Hospitl Universitario Marqués de Valdecilla; 🇪🇸 Santander, Cantabria, Spain