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Non-alcoholic steatohepatitis (NASH) is a growing public health problem that affects more than 5% of the population and can lead to cirrhosis and hepatocellular carcinoma. These patients are at greater risk of cardiovascular and hepatic death, and higher rates of neoplasms, both gastrointestinal and extra-intestinal. The standard treatment is weight loss with diet and physical exercise, which has shown a histological and analytical improvement in patients who achieve a 5-10% reduction in body weight. However, less than 25% of subjects achieve this goal. Restrictive surgical treatments and gastric bypass have achieved, in obese patients, an improvement in metabolic syndrome, insulin resistance and liver histology, but in patients with liver cirrhosis the morbidity-mortality of this surgery is high. Currently, endoscopic techniques are being developed, which are less invasive and have fewer complications, and which also achieve gastric restriction with similar characteristics to those obtained by the surgical method. Among them is the tubulization or vertical gastroplasty with the OverStitch system (Apollo Endosurgery, Austin, TX, USA). However, this method has not been evaluated in patients with obesity and/or metabolic syndrome and NASH cirrhosis. For this reason, the main objective of the investigators study is to evaluate the safety and efficacy of endoscopic gastroplasty in improving metabolic factors and liver histology in patients with obesity with or without metabolic syndrome and NASH-compensated cirrhosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Endoscopic vertical gastroplasty | Proof-of-concept study that will prospectively include a number of patients undergoing endoscopic vertical gastroplasty + lifestyle modifications to evaluate the effect of this technique in an adult population with obesity and NASH cirrhosis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Endoscopic vertical gastroplasty | Procedure | endoscopic vertical gastroplasty + lifestyle modification |
|
| Measure | Description | Time Frame |
|---|---|---|
| To evaluate the safety of endoscopic vertical gastroplasty + lifestyle modification | Number of adverse events resulting from the procedure during the study | 96 weeks |
| To evaluate the safety of endoscopic vertical gastroplasty + lifestyle modification | Number of events related to liver disease: ascites, bleeding secondary to PTH, encephalopathy, SBP, or renal failure | 96 weeks |
| To evaluate the safety of endoscopic vertical gastroplasty + lifestyle modification | Number of cardiovascular events during follow-up: Ischemic heart disease, stroke, peripheral arterial disease, heart failure, cardiomyopathy. | 96 weeks |
| Number of the patients to evaluate the safety of endoscopic vertical gastroplasty + lifestyle modification | Death from all causes | 96 weeks |
| Number of the patients to evaluate the safety of endoscopic vertical gastroplasty + lifestyle modification | Liver transplant | 96 weeks |
| Number of the patients to evaluate the safety of endoscopic vertical gastroplasty + lifestyle modification | Model for end-stage liver disease (MELD) ≥ 15. | 96 weeks |
| To evaluate the safety of endoscopic vertical gastroplasty + lifestyle modification | Worsening of the Child-Pugh score by at least 2 points |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the following histological changes of treatment according to NASH-CRN criteria | Changes in fibrosis including: improvement, not worsening, and progression | after 96 weeks |
| Evaluate the following histological changes of treatment according to NASH-CRN criteria |
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Inclusion Criteria:
1) Subjects between the ages of 18 and 65 (inclusive) at the time of the first selection visit 2) They must provide a signed written informed consent and agree to comply with the study protocol.
3) Subjects with a BMI greater than 30 kg/m2 whether or not associated with metabolic risk factors (MD, hypertension, dyslipemia).
4) Confirmed diagnosis of non-alcoholic steatohepatitis with a degree of fibrosis 4 according to the NASH CRN staging system in a liver biopsy obtained in the 12 months prior to the endoscopic procedure or during the screening period.
5) Absence of other causes of chronic liver disease (alcoholic, viral, autoimmune, cholestatic disease, Wilson's disease, α1AT deficit, hemochromatosis)
Exclusion Criteria:
14) Pregnancy. 15) Refusal to give informed consent. 16) Any medical condition that could reduce life expectancy to less than 2 years, including known cancers.
17) Indications of any other untreated, unstable or clinically significant immunological, endocrine, haematological, gastrointestinal, neurological, neoplastic or psychiatric disease.
18) Mental instability or incompetence such that the validity of the informed consent or the ability to comply with the study is uncertain.
19) Positive antibodies to human immunodeficiency virus. 20) Data on decompensated liver disease:
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Given the lack of previous studies on the efficacy of this technique in this type of patient, this proof-of-concept study will include a relatively small number of patients in order to obtain safety data and preliminary estimates of efficacy.
Patients must present with obesity (BMI ≥ 30) associated or not with a metabolic syndrome according to NCEP ATP III criteria, which is already an indication for endoscopic treatment, and the diagnosis of cirrhosis by NASH according to histology (See inclusion criteria), which is a relative contraindication for the performance of bariatric surgery.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Paula Iruzubieta, MD, PhD | Contact | 942204084 | p.iruzubieta@gmail.com | |
| Lucia Lavín Alconero, MBs, PhD | Contact | lucia.lavin@scren.es |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D009765 | Obesity |
| D005355 | Fibrosis |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D050177 | Overweight |
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| 96 weeks |
| Number of the patients to evaluate the safety of endoscopic vertical gastroplasty + lifestyle modification | Appearance of hepatocellular carcinoma (HCC) | 96 weeks |
| To evaluate the efficacy of endoscopic vertical gastroplasty + lifestyle modification in the histological improvement of fibrosis | using the percentage of subjects with improvement in at least 1 stage in fibrosis without worsening of NASH | 96 weeks |
Resolution of NASH defined as the presence or not of steatosis, without ballooning and with no or minimal inflammation. |
| after 96 weeks |
| Reduction the following histological changes of treatment according to NASH-CRN criteria | Improvement of at least 1 point in the different components of the NASH-CRN score (steatosis, liver ballooning, and lobular inflammation) | after 96 weeks |
| Evaluate the following histological changes of treatment according to NASH-CRN criteria | Improvement of fibrosis in at least 1 stage along with NASH improvement, defined as at least 1 stage improvement in fibrosis and at least 2 points less in NAFLD activity score (NAS) with at least 1 point improvement in ballooning and lobular swelling. | after 96 weeks |
| Evaluate the following histological changes of treatment according to NASH-CRN criteria | NAS score changes. | after 96 weeks |
| D044343 |
| Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010335 | Pathologic Processes |