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

NCT04060368 | Unknown

• 1 other identifier: TESLA-NASH
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Conditions

Non-alcoholic Steatohepatitis (NASH)

Keywords

NASH; Obesity; Endoscopic Sleeve Gastroplasty; Laparoscopic Sleeve Gastrectomy

Outcome Measures

Primary Outcomes (2)

• Proportion 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.

  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.

  Measurement at 96 weeks

Secondary Outcomes (27)

• Proportion of subjects undergoing ESG relative to LSG achieving improvement in liver histology according to the NASH-CRN scoring

  Measurement at 96 weeks

• Changes in the liver enzymes

  Measurement at 96 weeks

• Changes in lipid parameter

  Measurement at 96 weeks

• Changes in noninvasive markers of fibrosis and steatosis

  Measurement at 96 weeks

• Changes in noninvasive markers of fibrosis and steatosis

  Measurement at 96 weeks

Study Arms (2)

ESG Stitch® system + Lifestyle modifications

EXPERIMENTAL

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).

Procedure: Endoscopic Sleeve Gastroplasty (ESG) with OverStitch® system + Lifestyle modifications

LSG + Lifestyle modifications

ACTIVE COMPARATOR

Minimally invasive surgical technique defined as a gastric restriction by means of an excision approximately 80% of the stomach along the greater curvature.

Procedure: Laparoscopic Sleeve Gastrectomy (LSG) + Lifestyle modifications

Interventions

Endoscopic Sleeve Gastroplasty (ESG) with OverStitch® system + Lifestyle modifications PROCEDURE

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).

ESG Stitch® system + Lifestyle modifications

Laparoscopic Sleeve Gastrectomy (LSG) + Lifestyle modifications PROCEDURE

Minimally invasive surgical technique defined as a gastric restriction by means of an excision approximately 80% of the stomach along the greater curvature.

LSG + Lifestyle modifications

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects aged between 18 and 60 years (inclusive) at first screening visit.
• Must provide signed written informed consent and agree to comply with the study protocol.
• 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.
• 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
• 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
• 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)
• Patients agree to have 1 liver biopsy after 96 weeks after intervention

You may not qualify if:

• Known heart failure (Grade I to IV of the classification of the New York Heart Association).
• History of efficient bariatric surgery within 10 years prior to Screening.
• 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).
• Weight loss of more than 5% in the 6 months prior to randomization.
• 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.
• Liver cirrhosis.
• Non-cirrhotic portal hypertension.
• Esophagogastric varices.
• Hepatocellular carcinoma
• Portal thrombosis.
• Pregnancy.
• Refusal to give informed consent.
• Any medical condition that could reduce life expectancy to less than 2 years, including known cancers.
• Signs of any other unstable or clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric disease without treatment.
• Instability or mental incompetence, so that the validity of the informed consent or the ability to comply with the study are uncertain.

Sponsors & Collaborators

• Instituto de Investigación Marqués de Valdecilla: lead

Study Sites (1)

Hospitl Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

RECRUITING

Related Publications (7)

• Cuadrado A, Orive A, Garcia-Suarez C, Dominguez A, Fernandez-Escalante JC, Crespo J, Pons-Romero F. Non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma. Obes Surg. 2005 Mar;15(3):442-6. doi: 10.1381/0960892053576596.

  PMID: 15826485 RESULT

• Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015 Apr;13(4):643-54.e1-9; quiz e39-40. doi: 10.1016/j.cgh.2014.04.014. Epub 2014 Apr 24.

  PMID: 24768810 RESULT

• Pais R, Charlotte F, Fedchuk L, Bedossa P, Lebray P, Poynard T, Ratziu V; LIDO Study Group. A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver. J Hepatol. 2013 Sep;59(3):550-6. doi: 10.1016/j.jhep.2013.04.027. Epub 2013 May 9.

  PMID: 23665288 RESULT

• Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.

  PMID: 21623852 RESULT

• 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.

  PMID: 16899321 RESULT

• 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.

  PMID: 16197788 RESULT

• 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.

  PMID: 34717726 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Javier Crespo, PROF

CONTACT

+34942204089; javier.crespo@scsalud.es

Paula Iruzubieta, MD, PhD

CONTACT

+34942204089; p.iruzubieta@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Javier Crespo

Model Details: Experimental: Endoscopic Sleeve Gastroplasty with OverStitch® system + Lifestyle modifications Comparator: Laparoscopic Sleeve Gastrectomy + Lifestyle modifications

Study Record Dates

• First Submitted: July 18, 2019
• First Posted: August 19, 2019
• Study Start: June 1, 2020
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2023
• Last Updated: September 30, 2020

Record last verified: 2020-09

Locations

ES (1)