Multicenter, Randomized, Controlled and Double-blind Study of Efficacy and Safety of Endoscopic Gastric Tubulization in Patients With Non-alcoholic Steatohepatitis (NASH-APOLLO).

NCT03426111 | Unknown DMC

• 1 other identifier: PI17-00499
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Nonalcoholic steatohepatitis is a growing public health problem affecting over 5% of the population. These patients are at increased risk of cardiovascular and liver-related death and have higher rates of malignancy. The currently standard of care is weight loss and physical exercise, with histological and analytical improvement in patients achieving a 5-10% reduction in body weight. However, less than 25% of the subjects achieve this goal. In obese patients , restrictive surgical treatments and gastric bypass have been successful in improving the metabolic syndrome, insulin resistance and liver histology. Currently, less invasive and less costly endoscopic techniques are being developed. These techniques also achieve a gastric restriction with similar results than bariatric surgery. One of these is the OverStitch® system (Apollo Endosurgery, Austin, TX, USA). Our aim is to evaluate the efficacy and safety of this method in the improvement of liver histology in obese patients with nonalcoholic steatohepatitis.

Conditions

Non-Alcoholic Fatty Liver Disease; Obesity

Keywords

Non-Alcoholic Fatty Liver Disease; NASH; Obesity; Endoscopic gastric tubulization; Non-alcoholic steatohepatitis

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy of gastric tubulization + modification in lifestyle for 72 weeks compared to standard treatment / placebo in the resolution of NASH 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.

  72 weeks

Secondary Outcomes (12)

• Number of patients with improvement of fibrosis according to the CRN score NASH.

  72 weeks

• Non alcoholic fatty liver disease (NASH) activity score (NAS).

  72 weeks

• steatosis-activity-fibrosis index score (steatosis activity fibrosis, SAF).

  72 weeks

• Cardiovascular and death events related to the liver

  72 weeks

• Changes in liver enzymes

  72 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Diagnostic upper endoscopy plus lifestyle modification.

Behavioral: Lifestyle modification

Treatment

ACTIVE COMPARATOR

Endoscopic gastric tubulization with OverStitch® system (Apollo Endosurgery, Austin, TX, USA) plus lifestyle modification.

Device: Endoscopic Gastric Tubulization with OverStitch® system (Apollo Endosurgery, Austin, TX, USA); Behavioral: Lifestyle modification

Interventions

Endoscopic Gastric Tubulization with OverStitch® system (Apollo Endosurgery, Austin, TX, USA) DEVICE

This endoscopic technique is defined as a gastric restriction by means of sutures of the entire gastric wall, 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).

Treatment

Lifestyle modification BEHAVIORAL

Hypocaloric diet and moderate physical exercise

Placebo; Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged between 18 and 75 years (inclusive) at the time of the first screening visit.
• They must provide signed written informed consent and agree to comply the study protocol
• Body mass index\> 30 kg / m².
• 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 fibrosis of 0 to \<4, according to the staging system of CRN fibrosis on NASH.
• NAS score ≥ 4.
• For patients without fibrosis or with stage 1 fibrosis, the NAS score≥5 and one of the following conditions (metabolic syndrome (definition NCEP ATP III), DM type II, HOMA-IR\> 6).
• The liver biopsy should have been done with a 16 G trucut needle and the minimum size should be 25 mm.

You may not qualify if:

• Known heart failure (Grade I to IV of the classification of the New York Heart Association).
• History of effective bariatric surgery in the 5 years prior to selection.
• 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.
• Liver cirrhosis.
• Non-cirrhotic portal hypertension.
• 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.
• 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

• Puerta de Hierro University Hospital: lead
• Hospital Universitario Ramon y Cajal: collaborator
• Hospital Universitario Marqués de Valdecilla: collaborator
• Hospitales Universitarios Virgen del Rocío: collaborator

Study Sites (1)

Jose Luis Calleja

Majadahonda, Madrid, 28222, Spain

RECRUITING

Related Publications (18)

• Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84. doi: 10.1002/hep.28431. Epub 2016 Feb 22.

  PMID: 26707365 BACKGROUND

• Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology. 1990 Nov;12(5):1106-10. doi: 10.1002/hep.1840120505.

  PMID: 2227807 BACKGROUND

• Stepanova M, Rafiq N, Makhlouf H, Agrawal R, Kaur I, Younoszai Z, McCullough A, Goodman Z, Younossi ZM. Predictors of all-cause mortality and liver-related mortality in patients with non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci. 2013 Oct;58(10):3017-23. doi: 10.1007/s10620-013-2743-5. Epub 2013 Jun 18.

  PMID: 23775317 BACKGROUND

• Michelotti GA, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):656-65. doi: 10.1038/nrgastro.2013.183. Epub 2013 Oct 1.

  PMID: 24080776 BACKGROUND

• Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol. 2005 Jan;42(1):132-8. doi: 10.1016/j.jhep.2004.09.012.

  PMID: 15629518 BACKGROUND

• Angulo P. Diagnosing steatohepatitis and predicting liver-related mortality in patients with NAFLD: two distinct concepts. Hepatology. 2011 Jun;53(6):1792-4. doi: 10.1002/hep.24403. No abstract available.

  PMID: 21557278 BACKGROUND

• Neuschwander-Tetri BA. Non-alcoholic fatty liver disease. BMC Med. 2017 Feb 28;15(1):45. doi: 10.1186/s12916-017-0806-8.

  PMID: 28241825 BACKGROUND

• Gallego-Duran R, Cerro-Salido P, Gomez-Gonzalez E, Pareja MJ, Ampuero J, Rico MC, Aznar R, Vilar-Gomez E, Bugianesi E, Crespo J, Gonzalez-Sanchez FJ, Aparcero R, Moreno I, Soto S, Arias-Loste MT, Abad J, Ranchal I, Andrade RJ, Calleja JL, Pastrana M, Iacono OL, Romero-Gomez M. Imaging biomarkers for steatohepatitis and fibrosis detection in non-alcoholic fatty liver disease. Sci Rep. 2016 Aug 12;6:31421. doi: 10.1038/srep31421.

  PMID: 27514671 BACKGROUND

• Barr J, Caballeria J, Martinez-Arranz I, Dominguez-Diez A, Alonso C, Muntane J, Perez-Cormenzana M, Garcia-Monzon C, Mayo R, Martin-Duce A, Romero-Gomez M, Lo Iacono O, Tordjman J, Andrade RJ, Perez-Carreras M, Le Marchand-Brustel Y, Tran A, Fernandez-Escalante C, Arevalo E, Garcia-Unzueta M, Clement K, Crespo J, Gual P, Gomez-Fleitas M, Martinez-Chantar ML, Castro A, Lu SC, Vazquez-Chantada M, Mato JM. Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression. J Proteome Res. 2012 Apr 6;11(4):2521-32. doi: 10.1021/pr201223p. Epub 2012 Mar 15.

  PMID: 22364559 BACKGROUND

• Alkhouri N, Feldstein AE. Noninvasive diagnosis of nonalcoholic fatty liver disease: Are we there yet? Metabolism. 2016 Aug;65(8):1087-95. doi: 10.1016/j.metabol.2016.01.013. Epub 2016 Feb 2.

  PMID: 26972222 BACKGROUND

• Nobili V, Parkes J, Bottazzo G, Marcellini M, Cross R, Newman D, Vizzutti F, Pinzani M, Rosenberg WM. Performance of ELF serum markers in predicting fibrosis stage in pediatric non-alcoholic fatty liver disease. Gastroenterology. 2009 Jan;136(1):160-7. doi: 10.1053/j.gastro.2008.09.013. Epub 2008 Sep 20.

  PMID: 18992746 BACKGROUND

• Ratziu V, Massard J, Charlotte F, Messous D, Imbert-Bismut F, Bonyhay L, Tahiri M, Munteanu M, Thabut D, Cadranel JF, Le Bail B, de Ledinghen V, Poynard T; LIDO Study Group; CYTOL study group. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 2006 Feb 14;6:6. doi: 10.1186/1471-230X-6-6.

  PMID: 16503961 BACKGROUND

• Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, Friedman SL, Diago M, Romero-Gomez M. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology. 2015 Aug;149(2):367-78.e5; quiz e14-5. doi: 10.1053/j.gastro.2015.04.005. Epub 2015 Apr 10.

  PMID: 25865049 BACKGROUND

• Klebanoff MJ, Corey KE, Chhatwal J, Kaplan LM, Chung RT, Hur C. Bariatric surgery for nonalcoholic steatohepatitis: A clinical and cost-effectiveness analysis. Hepatology. 2017 Apr;65(4):1156-1164. doi: 10.1002/hep.28958. Epub 2017 Feb 21.

  PMID: 27880977 BACKGROUND

• Mummadi RR, Kasturi KS, Chennareddygari S, Sood GK. Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2008 Dec;6(12):1396-402. doi: 10.1016/j.cgh.2008.08.012. Epub 2008 Aug 19.

  PMID: 18986848 BACKGROUND

• ASGE Bariatric Endoscopy Task Force; ASGE Technology Committee; Abu Dayyeh BK, Edmundowicz SA, Jonnalagadda S, Kumar N, Larsen M, Sullivan S, Thompson CC, Banerjee S. Endoscopic bariatric therapies. Gastrointest Endosc. 2015 May;81(5):1073-86. doi: 10.1016/j.gie.2015.02.023. Epub 2015 Mar 28. No abstract available.

  PMID: 25828245 BACKGROUND

• ASGE/ASMBS Task Force on Endoscopic Bariatric Therapy; Ginsberg GG, Chand B, Cote GA, Dallal RM, Edmundowicz SA, Nguyen NT, Pryor A, Thompson CC. A pathway to endoscopic bariatric therapies. Gastrointest Endosc. 2011 Nov;74(5):943-53. doi: 10.1016/j.gie.2011.08.053. No abstract available.

  PMID: 22032311 BACKGROUND

• Abad J, Llop E, Arias-Loste MT, Burgos-Santamaria D, Martinez Porras JL, Iruzubieta P, Graus J, Ruiz-Antoran B, Sanchez Yuste MR, Romero-Gomez M, Albillos A, Crespo J, Calleja JL. Endoscopic Sleeve Gastroplasty Plus Lifestyle Intervention in Patients With Metabolic Dysfunction-associated Steatohepatitis: A Multicenter, Sham-controlled, Randomized Trial. Clin Gastroenterol Hepatol. 2025 Aug;23(9):1556-1566.e3. doi: 10.1016/j.cgh.2024.10.027. Epub 2024 Dec 16.

  PMID: 39694202 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

Jose Luis Calleja, Prof

CONTACT

+34911916000; joseluis.calleja@uam.es

Javier Abad, MD

CONTACT

+34650814289; jabad@salud.madrid.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Head of Hepatology Unit of Puerta de Hierro University Hospital

Model Details: Multicenter, randomized,controlled and double-blind study with two parallel arms, placebo (normal endoscopy and lifestyle modification) or endoscopic gastric tubulization with OverStitch® system (Apollo Endosurgery, Austin, TX, USA) and lifestyle modification.

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: February 8, 2018
• Study Start: April 18, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: December 12, 2018

Record last verified: 2018-12

Locations

ES (1)