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

December 10, 2018 updated by: Jose Luis Calleja, Puerta de Hierro University Hospital

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Recruiting
        • Jose Luis Calleja
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jose Luis Calleja, Prof
        • Sub-Investigator:
          • Elba Llop, PhD
        • Sub-Investigator:
          • Jose Luis Martinez, PhD
        • Sub-Investigator:
          • Marta Hernandez, MD
        • Sub-Investigator:
          • Javier Abad, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men or women aged between 18 and 75 years (inclusive) at the time of the first screening visit.
  2. They must provide signed written informed consent and agree to comply the study protocol
  3. Body mass index> 30 kg / m².
  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 fibrosis of 0 to <4, according to the staging system of CRN fibrosis on NASH.
  5. NAS score ≥ 4.
  6. 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).
  7. The liver biopsy should have been done with a 16 G trucut needle and the minimum size should be 25 mm.

Exclusion Criteria:

  1. Known heart failure (Grade I to IV of the classification of the New York Heart Association).
  2. History of effective bariatric surgery in the 5 years prior to selection.
  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. Liver cirrhosis.
  6. Non-cirrhotic portal hypertension.
  7. 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.
  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.

    In addition to the above criteria, the patient must not present any of the following biological exclusion criteria:

  16. Antibodies positive for the human immunodeficiency virus.
  17. Aspartate aminotransferase (AST) and / or ALT> 10 x upper limit of normal (ULN).
  18. Total bilirubin> 25 μmol / l (1.5 mg / dl).
  19. Standardized international index> 1.4.
  20. Platelet count <100 000 / mm3.
  21. Serum creatinine levels> 135 μmol / l (> 1.53 mg / dl) in men and> 110 μmol / l (> 1.24 mg / dl) in women.
  22. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Diagnostic upper endoscopy plus lifestyle modification.
Behavioral: Lifestyle modification
Hypocaloric diet and moderate physical exercise
ACTIVE_COMPARATOR: Treatment
Endoscopic gastric tubulization with OverStitch® system (Apollo Endosurgery, Austin, TX, USA) plus lifestyle modification.
Behavioral: Lifestyle modification
Hypocaloric diet and moderate physical exercise
Device: Endoscopic Gastric Tubulization with OverStitch® system (Apollo Endosurgery, Austin, TX, USA)
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 72 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with improvement of fibrosis according to the CRN score NASH.
Time Frame: 72 weeks
to evaluate other histological changes after 72 weeks of treatment (CRN)
72 weeks
Non alcoholic fatty liver disease (NASH) activity score (NAS).
Time Frame: 72 weeks
Number of patients with improvement in histological scores CRN score on NASH (NAS)
72 weeks
steatosis-activity-fibrosis index score (steatosis activity fibrosis, SAF).
Time Frame: 72 weeks
Number of patients with improvement in the SAF score.
72 weeks
Cardiovascular and death events related to the liver
Time Frame: 72 weeks
To evaluate the CV events in patients treated with gastric endoscopic tubulization + lifestyle modification with respect to lifestyle modification / placebo
72 weeks
Changes in liver enzymes
Time Frame: 72 weeks
To evaluate liver enzymes in patients treated with gastric endoscopic tubulization + lifestyle modification with respect to lifestyle modification / placebo
72 weeks
Changes in the noninvasive markers of fibrosis and steatosis
Time Frame: 72 weeks
To evaluate the noninvasive markers in patients treated with gastric endoscopic tubulization + lifestyle modification with respect to lifestyle modification / placebo
72 weeks
Changes in lipid parameters
Time Frame: 72 weeks
To evaluate the lipid parameters in patients treated with gastric endoscopic tubulization + lifestyle modification with respect to lifestyle modification / placebo
72 weeks
Variation in body weight
Time Frame: 72 weeks
To evaluate body weight in patients treated with gastric endoscopic tubulization + lifestyle modification with respect to lifestyle modification / placebo
72 weeks
Biomarkers of endothelial and macrophage dysfunction
Time Frame: 72 weeks
To evaluate macrophage function in patients treated with gastric endoscopic tubulization + lifestyle modification with respect to lifestyle modification / placebo
72 weeks
Changes in markers of homeostasis of glucose and insulin resistance
Time Frame: 72 weeks
To evaluate the glucose metabolism in patients treated with gastric endoscopic tubulization + lifestyle modification with respect to lifestyle modification / placebo
72 weeks
Changes in cardiovascular risk profile
Time Frame: 72 weeks
To evaluate cardiovascular risk profile in patients treated with gastric endoscopic tubulization + lifestyle modification with respect to lifestyle modification / placebo
72 weeks
Changes in quality of life (abbreviated health questionnaire SF-36).
Time Frame: 72 weeks
To evaluate the following endpoints in patients treated with gastric endoscopic tubulization + lifestyle modification with respect to lifestyle modification / placebo
72 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Puerta de Hierro University Hospital

Collaborators

Hospital Universitario Ramon y Cajal
Hospitales Universitarios Virgen del Rocío
Hospital Universitario Marqués de Valdecilla

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 18, 2018

Primary Completion (ANTICIPATED)

December 1, 2020

Study Completion (ANTICIPATED)

December 1, 2020

Study Registration Dates

First Submitted

January 9, 2018

First Submitted That Met QC Criteria

February 1, 2018

First Posted (ACTUAL)

February 8, 2018

Study Record Updates

Last Update Posted (ACTUAL)

December 12, 2018

Last Update Submitted That Met QC Criteria

December 10, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PI17-00499

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Obesity

Clinical Trials on Lifestyle modification

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Gabon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe