NCT04281303

Brief Summary

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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
10

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Apr 2020

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 20, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 24, 2020

Completed
1 month until next milestone

Study Start

First participant enrolled

April 1, 2020

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2021

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2022

Completed
Last Updated

February 25, 2020

Status Verified

February 1, 2020

Enrollment Period

1 year

First QC Date

February 20, 2020

Last Update Submit

February 24, 2020

Conditions

Keywords

NASHObesityendoscopic vertical gastroplastycirrhosis

Outcome Measures

Primary Outcomes (9)

  • 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

    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

Secondary Outcomes (5)

  • Evaluate the following histological changes of treatment according to NASH-CRN criteria

    after 96 weeks

  • Evaluate the following histological changes of treatment according to NASH-CRN criteria

    after 96 weeks

  • Reduction the following histological changes of treatment according to NASH-CRN criteria

    after 96 weeks

  • Evaluate the following histological changes of treatment according to NASH-CRN criteria

    after 96 weeks

  • Evaluate the following histological changes of treatment according to NASH-CRN criteria

    after 96 weeks

Study Arms (1)

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

Procedure: Endoscopic vertical gastroplasty

Interventions

endoscopic vertical gastroplasty + lifestyle modification

Endoscopic vertical gastroplasty

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

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.

You may qualify if:

  • \) 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.
  • \) Subjects with a BMI greater than 30 kg/m2 whether or not associated with metabolic risk factors (MD, hypertension, dyslipemia).
  • \) 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.
  • \) Absence of other causes of chronic liver disease (alcoholic, viral, autoimmune, cholestatic disease, Wilson's disease, α1AT deficit, hemochromatosis)

You may not qualify if:

  • Current or past history of any liver decompensation event (ascites, hepatic encephalopathy, variceal bleeding, hepatorenal syndrome, hepatopulmonary syndrome).
  • Child-Pugh Scale ≥ 7 points.
  • MELD scale \> 12
  • Documented presence of varicose veins based on a previous endoscopy performed in the 6 months prior to the intervention.
  • Documented presence of collateral circulation based on an echoendoscopy and/or thoraco-abdominal CT with 3D reconstruction performed in the selection period.
  • Presence of a hepatic venous pressure gradient (HVPG) ≥ 10 mmHg in a hemodynamic study performed in the 4 months prior to surgery or in the selection period.
  • Known heart failure (Grade I-IV of the New York Heart Association classification).
  • History of bariatric surgery
  • Patients with a history of clinically significant cardiovascular events in the 6 months prior to the endoscopic procedure, such as an acute cardiovascular event, stroke, transient ischemic attack, or coronary heart disease (angina, myocardial infarction, revascularization procedures).
  • Weight loss of more than 5 % in the 6 months prior to the operation.
  • Recent or current history of significant consumption of alcoholic beverages (\< 5 years) For men, significant consumption is usually defined as more than 30 g of pure alcohol per day. For women, it is normally defined as more than 20 g of pure alcohol per day.
  • Hepatocarcinoma. (13) Portal thrombosis.
  • \) Pregnancy. 15) Refusal to give informed consent. 16) Any medical condition that could reduce life expectancy to less than 2 years, including known cancers.
  • \) Indications of any other untreated, unstable or clinically significant immunological, endocrine, haematological, gastrointestinal, neurological, neoplastic or psychiatric disease.
  • \) Mental instability or incompetence such that the validity of the informed consent or the ability to comply with the study is uncertain.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Non-alcoholic Fatty Liver DiseaseObesityFibrosis

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System DiseasesOverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsPathologic Processes

Central Study Contacts

Paula Iruzubieta, MD, PhD

CONTACT

Lucia Lavín Alconero, MBs, PhD

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 20, 2020

First Posted

February 24, 2020

Study Start

April 1, 2020

Primary Completion

April 1, 2021

Study Completion

April 1, 2022

Last Updated

February 25, 2020

Record last verified: 2020-02