Clinical trial NCT04060368: Efficacy and Safety of Endoscopic Sleeve Gastroplasty Versus Laparoscopic Sleeve Gastrectomy in Obese Subjects With NASH
Official title: STudy to Evaluate the Efficacy and Safety of Endoscopic Sleeve Gastroplasty (ESG) Versus LAparoscopic Sleeve Gastrectomy (LSG) in Obese Subjects With Non-Alcoholic SteatoHepatitis (NASH)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non-alcoholic Steatohepatitis (NASH)
Keywords: NASH
Obesity
Endoscopic Sleeve Gastroplasty
Laparoscopic Sleeve Gastrectomy
Lead sponsor: Instituto de Investigación Marqués de Valdecilla
Sponsor class: OTHER
First posted: 2019-08-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental: Endoscopic Sleeve Gastroplasty with OverStitch® system + Lifestyle modifications Comparator: Laparoscopic Sleeve Gastrectomy + Lifestyle modifications
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of subjects undergoing ESG relative to LSG achieving resolution of NASH without worsening of fibrosis
timeFrame: Measurement at 96 weeks
measure: Proportion of subjects undergoing ESG relative to LSG with cardiovascular and liver-related death events
timeFrame: Measurement at 96 weeks
Secondary outcomes:
measure: Proportion of subjects undergoing ESG relative to LSG achieving improvement in liver histology according to the NASH-CRN scoring
timeFrame: Measurement at 96 weeks
measure: Changes in the liver enzymes
timeFrame: Measurement at 96 weeks
measure: Changes in lipid parameter
timeFrame: Measurement at 96 weeks
measure: Changes in noninvasive markers of fibrosis and steatosis
timeFrame: Measurement at 96 weeks
measure: Changes in noninvasive markers of fibrosis and steatosis
timeFrame: Measurement at 96 weeks
measure: Changes in noninvasive markers of fibrosis and steatosis
timeFrame: Measurement at 96 weeks
measure: Changes in noninvasive markers of fibrosis and steatosis
timeFrame: Measurement at 96 weeks
measure: Changes in noninvasive markers of fibrosis and steatosis
timeFrame: Measurement at 96 weeks
measure: Changes in noninvasive markers of fibrosis and steatosis
timeFrame: Measurement at 96 weeks
measure: Changes in body weight
timeFrame: Measurement at 96 weeks
measure: Changes in inflammatory markers
timeFrame: Measurement at 96 weeks
measure: Changes in inflammatory markers
timeFrame: Measurement at 96 weeks
measure: Changes in inflammatory markers
timeFrame: Measurement at 96 weeks
measure: Changes in inflammatory markers
timeFrame: Measurement at 96 weeks
measure: Changes in inflammatory markers
timeFrame: Measurement at 96 weeks
measure: Changes in inflammatory markers
timeFrame: Measurement at 96 weeks
measure: Changes in serum expression of incretins
timeFrame: Measurement at 96 weeks
measure: Changes in mineral metabolism parameters.
timeFrame: Measurement at 96 weeks
measure: Changes in gut microbiota
timeFrame: Measurement at 96 weeks
measure: Changes in glucose homeostasis markers and insulin resistance
timeFrame: Measurement at 96 weeks
measure: Changes in glucose homeostasis markers and insulin resistance
timeFrame: Measurement at 96 weeks
measure: Changes in glucose homeostasis markers and insulin resistance
timeFrame: Measurement at 96 weeks
measure: Changes in glucose homeostasis markers and insulin resistance
timeFrame: Measurement at 96 weeks
measure: Changes in glucose homeostasis markers and insulin resistance
timeFrame: Measurement at 96 weeks
measure: Changes in glucose homeostasis markers and insulin resistance
timeFrame: Measurement at 96 weeks
measure: Changes in glucose homeostasis markers and insulin resistance
timeFrame: Measurement at 96 weeks
measure: Incidence of adverse events
timeFrame: Measurement at 96 weeks
Other outcomes:
Locations:
city: Santander
country: Spain
facility: Hospitl Universitario Marqués de Valdecilla
state: Cantabria
Study officials:
References:
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citation: Machado M, Marques-Vidal P, Cortez-Pinto H. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol. 2006 Oct;45(4):600-6. doi: 10.1016/j.jhep.2006.06.013. Epub 2006 Jul 25.
citation: Boza C, Riquelme A, Ibanez L, Duarte I, Norero E, Viviani P, Soza A, Fernandez JI, Raddatz A, Guzman S, Arrese M. Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass. Obes Surg. 2005 Sep;15(8):1148-53. doi: 10.1381/0960892055002347.
citation: Lavin-Alconero L, Fernandez-Lanas T, Iruzubieta-Coz P, Arias-Loste MT, Rodriguez-Duque JC, Rivas C, Cagigal ML, Montalban C, Useros AL, Alvarez-Cancelo A, Garcia-Saiz M, Crespo-Garcia J. Efficacy and safety of endoscopic sleeve gastroplasty versus laparoscopic sleeve gastrectomy in obese subjects with Non-Alcoholic SteatoHepatitis (NASH): study protocol for a randomized controlled trial (TESLA-NASH study). Trials. 2021 Oct 30;22(1):756. doi: 10.1186/s13063-021-05695-7.