Evaluation of an Endoscopic Sutured Gastroplasty in Patients With NonAlcoholic Steatohepatitis (NASH) and Fibrosis.

NCT04653311 | Unknown DMC

• 1 other identifier: P2019/400 / B406201941027
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases characterized by liver steatosis which can, in a minority of patients, progress to nonalcoholic steatohepatitis (NASH), fibrosis, and ultimately hepatocellular carcinoma and liver failure. NASH is also recognized as an independent cardiovascular risk factor. Currently, weight loss is the only validated treatment for NASH and also positively affect all the features of metabolic syndrome. Considering the known positive metabolic effects of bariatric surgery, efforts have been exerted to develop minimally endoscopic procedures aiming to induce weight loss. Therefore, we would like to evaluate in patients with NASH disease and fibrosis, the impact of an endoscopic sutured gastroplasty (with Endomina® device) on:

• Mainly liver histological endpoints but also,
• Surrogate markers of hepatic inflammation and fibrosis and
• Surrogate markers of insulin resistance as well as fasting lipid and glycemic profiles.

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Rate of disappearance of NASH without worsening of fibrosis grade

  Diagnosis of NASH at the liver biopsy

  at 48 weeks

Secondary Outcomes (17)

• Incidence of all Adverse Device Effects

  at 48 weeks

• Change in th SF-46 quality of life score

  at 48 weeks

• Change in the NAS (NAFLD activity score) score

  at 48 weeks

• Change in liver histologic characteristics, such as steatosis, ballooning, lobular inflammation, and portal chronic inflammation scores.

  at 48 weeks

• Weight loss from randomization to the end of treatment

  at 48 weeks

Study Arms (2)

Endomina procedure + lifestyle intervention

EXPERIMENTAL

The procedure will be performed under general anesthesia with tracheal intubation. Endomina will be introduced into the stomach over a guidewire and then fixed to the endoscope. This group will also receive the medical standard treatment defined as lifestyle intervention.

Device: Endomina®

Lifestyle intervention

NO INTERVENTION

The group will receive the medical standard treatment defined as lifestyle therapy combining diet (mediterranean diet) with increased physical activity

Interventions

Endomina® DEVICE

Endoscopic sleeve gastroplasty (Endomina) at J0 with multidisciplinary follow-up for 1 year

Endomina procedure + lifestyle intervention

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI between 27 to 40 kg/m².
• Histological confirmation of steatohepatitis on a diagnostic liver biopsy by central reading of the slides (biopsy obtained within 6 months prior to Screening or during the Screening Period) with at least 1 in each component of the NAS (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).
• NAS ≥4.
• Fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging system.
• Patients in whom it is safe and practical to proceed with a liver biopsy (in accordance with the current guidelines), and who agree to have:
• liver biopsy during the Screening Period for diagnostic purpose (if no historical biopsy within 6 months before screening is available)
• a final liver biopsy after 1 year of treatment for assessment of the treatment effects on NASH and fibrosis
• For patients with type 2 diabetes, glycemia must be controlled (HbA1c \< 9.0%). If glycemia is controlled by antidiabetic drugs, change in anti-diabetic therapy must follow these requirements:
• No qualitative change 6 months prior to diagnostic liver biopsy up to Randomization (i.e., implementation of a new anti-diabetic therapy) for patients treated with metformin, gliptins, sulfonylureas, sodium/glucose cotransporter (SGLT) 2 inhibitors, glucagon-like peptide (GLP)-1 agonists or insulin. Dose changes of these medications are allowed in the 6 months prior to diagnostic liver biopsy, except for GLP-1 agonists, which must remain on stable dose in the 6 months prior to diagnostic liver biopsy.
• No implementation of GLP-1 agonists and SGLT2 inhibitors up to 1 year.
• Initiation of any other antidiabetic drugs is allowed after randomization based on treating physicians' judgment, except for glitazones which are prohibited 6 months prior to diagnostic liver biopsy until the end of treatment.
• Must be able to comply with all study requirements for the duration of the study as outlined in the protocol. This includes complying with the visit schedule as well as study specific procedures such as: clinical assessment, endoscopy, radiography, as well as laboratory investigations.
• Must be able to understand and be willing to provide written informed consent.
• Must live within 75 km of the treatment site.
• In case of obesity, had followed the bariatric multidisciplinary workup (blood analyses, dietician,psychologist and doctor appointments).

You may not qualify if:

• Other well documented causes of chronic liver disease according to standard diagnostic procedures including, but not restricted to:
• Positive hepatitis B surface antigen (HBsAg)
• Positive HCV RNA, (tested for in case of known cured HCV infection, or positive HCV Ab at Screening)
• Suspicion of drug-induced liver disease
• Alcoholic liver disease
• Autoimmune hepatitis
• Wilson's disease
• Primary biliary cholangiopathy, primary sclerosing cholangitis
• Genetic homozygous hemochromatosis
• Presence of HCC
• History or planned liver transplant, or current MELD score \>12.
• Alpha-1 antitrypsin deficiency.
• Current or recent history (\< 5 years) of significant alcohol consumption. For men, significant consumption is defined as higher than 30g pure alcohol per day. For women, it is defined as higher than 20g pure alcohol per day.
• Compensated and decompensated cirrhosis (clinical and/or histological evidence of cirrhosis). Notably, NASH patients with fibrosis stage=4 according to the NASH CRN fibrosis staging system are excluded.
• Weight loss of more than 5 % within 6 months prior to randomization.

Sponsors & Collaborators

• Erasme University Hospital: lead
• Epidemiological and Clinical Research Information Network: collaborator

Study Sites (1)

CUB Hôpital Erasme

Brussels, 1070, Belgium

RECRUITING

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Jacques Deviere, MD, phD

  CUB Hôpital Erasme, Brussels, Belgium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alia Hadefi, MD

CONTACT

+325553714; alia.hadefi@erasme.ulb.ac.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The primary outcome will be blindly assessed at one year
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arm 1: Endomina procedure + lifestyle intervention Arm 2: Lifestyle intervention

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: December 4, 2020
• Study Start: June 23, 2020
• Primary Completion: June 23, 2023
• Study Completion: December 23, 2023
• Last Updated: February 2, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)