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

M

Majadahonda Iron Gate University

Status

Unknown

Conditions

Obesity
Non-Alcoholic Fatty Liver Disease

Treatments

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

Study type

Interventional

Funder types

Other

Identifiers

NCT03426111
PI17-00499

Details and patient eligibility

About

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.

Enrollment

40 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

40 participants in 2 patient groups, including a placebo group

Placebo
Placebo Comparator group
Description:
Diagnostic upper endoscopy plus lifestyle modification.
Treatment:
Behavioral: Lifestyle modification
Treatment
Active Comparator group
Description:
Endoscopic gastric tubulization with OverStitch® system (Apollo Endosurgery, Austin, TX, USA) plus lifestyle modification.
Treatment:
Behavioral: Lifestyle modification
Device: Endoscopic Gastric Tubulization with OverStitch® system (Apollo Endosurgery, Austin, TX, USA)

Trial contacts and locations

1

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Central trial contact

Jose Luis Calleja, Prof; Javier Abad, MD

Data sourced from clinicaltrials.gov

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