Multicenter, Randomized, Controlled and Double-blind Study of Efficacy and Safety of Endoscopic Gastric Tubulization in Patients With Non-alcoholic Steatohepatitis (NASH-APOLLO).
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- 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.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women aged between 18 and 75 years (inclusive) at the time of the first screening visit.
- •They must provide signed written informed consent and agree to comply the study protocol
- •Body mass index> 30 kg / m².
- •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.
- •NAS score ≥
- •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).
- •The liver biopsy should have been done with a 16 G trucut needle and the minimum size should be 25 mm.
排除标准
- •Known heart failure (Grade I to IV of the classification of the New York Heart Association).
- •History of effective bariatric surgery in the 5 years prior to selection.
- •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).
- •Weight loss of more than 5% in the 6 months prior to randomization.
- •Liver cirrhosis.
- •Non-cirrhotic portal hypertension.
- •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.
- •Esophagogastric varices.
- •Hepatocellular carcinoma
- •Portal thrombosis.
- •Refusal to give informed consent.
- •Any medical condition that could reduce life expectancy to less than 2 years, including known cancers.
- •Signs of any other unstable or clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric disease without treatment.
- •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:
- •Antibodies positive for the human immunodeficiency virus.
- •Aspartate aminotransferase (AST) and / or ALT> 10 x upper limit of normal (ULN).
- •Total bilirubin> 25 μmol / l (1.5 mg / dl).
- •Standardized international index> 1.
- •Platelet count <100 000 / mm
- •Serum creatinine levels> 135 μmol / l (> 1.53 mg / dl) in men and> 110 μmol / l (> 1.24 mg / dl) in women.
- •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.
结局指标
主要结局
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.
时间窗: 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.
次要结局
- steatosis-activity-fibrosis index score (steatosis activity fibrosis, SAF).(72 weeks)
- Changes in lipid parameters(72 weeks)
- Changes in markers of homeostasis of glucose and insulin resistance(72 weeks)
- Changes in quality of life (abbreviated health questionnaire SF-36).(72 weeks)
- Number of patients with improvement of fibrosis according to the CRN score NASH.(72 weeks)
- Cardiovascular and death events related to the liver(72 weeks)
- Variation in body weight(72 weeks)
- Biomarkers of endothelial and macrophage dysfunction(72 weeks)
- Non alcoholic fatty liver disease (NASH) activity score (NAS).(72 weeks)
- Changes in liver enzymes(72 weeks)
- Changes in the noninvasive markers of fibrosis and steatosis(72 weeks)
- Changes in cardiovascular risk profile(72 weeks)
研究者
Jose Luis Calleja
Professor and Head of Hepatology Unit of Puerta de Hierro University Hospital
Puerta de Hierro University Hospital