CTRI/2023/01/048844招募中不适用
Integrated multi-omics and machine learning to decipher pathobiology and outcomes in alcoholic hepatitis patients
ICMR1 个研究点 分布在 1 个国家目标入组 150 人开始时间: 2023年1月15日最近更新:
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Impact of GH along with standard medical therapy (SMT) as compared to SMT-alone on overall survival (Time frame 30 days)
研究概览
简要总结
- Background: Alcoholic liver disease (ALD) portends significant burden with 21.5 million life years lost every year. Alcoholic hepatitis (AH), a severe form of ALD, confers a high mortality (33-77% in 3 months). Aberrations in metabolism, immune response and gut bacterial translocation are major drivers of disease and its outcomes. Neutrophil dysfunction plays a key role in shaping organ failures and mortality in AH patients. However, literature is limited to biased and cross-sectional reporting of neutrophil dysfunction viz. impaired phenotype, phagocytosis, and extracellular traps in AH. And the trajectories of neutrophil dysfunction remain unclear. Therapies for AH are limited to abstinence, nutrition and steroids or liver transplant (selected cases), but are often in-effective or in-feasible in providing a long-term survival benefit.
- Novelty: We propose that unbiased and dynamic understanding of disease pathobiology hold a strong chance in improving outcomes of AH patients.
- Objectives: We aim to conduct extensive, unbiased and dynamic profiling of neutrophils at transcriptional and translational level employing high throughput multi-omics and machine learning strategies.
- Methods: First in the discovery phase, enrolled AH patients will be followed till 90days. Transcriptomic and proteomics of isolated neutrophils will be performed at baseline and at day-7. Differentially expressed genes and proteins associated with diseased condition and 90-day outcomes will be analyzed. Second, in the validation phase, relevant genes and proteins will be validated through qRT-PCR and ELISA in another cohort of AH patients.
- Expected outcome: We will ascertain AH and its mortality specific biologic signatures. These will be leveraged for novel therapeutics.
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients age 18 to 80 years
- •Patients with probable or definite alcoholic hepatitis (AH) (as per AASLD guidelines) will be enrolled from consecutive patients presenting first time to the department.
- •The diagnosis of AH will be made as per the NIAAA consensus, i.e., • onset of jaundice within the prior eight weeks, • ongoing consumption of >40g (female) or >60 (male)g of alcohol/day for 6 months or more, with less than 60 days of abstinence before the onset of jaundice • aspartate aminotransferase >50, aspartate aminotransferase/alanine aminotransferase >1.5, and both values <400IU/L • serum bilirubin (total) >3.0 mg/dL • liver biopsy confirmation in patients with confounding factors.
排除标准
- •Patients having: i.
- •HIV infection ii.
- •Prior organ transplantation iii.
- •Hepatic or extra-hepatic malignancy iv.
- •Receiving any experimental therapies v.
- •Pregnant or lactating women, will be excluded.
结局指标
主要结局
Impact of GH along with standard medical therapy (SMT) as compared to SMT-alone on overall survival (Time frame 30 days)
时间窗: 30 days and 90 days
次要结局
- Transcriptomic analysis of neutrophils to define molecular signatures linked to(pathophysiology and outcomes in alcoholic hepatitis (AH) patients. [Time frame: day-0 and day-7])
- Proteomic analysis of neutrophils towards unravelling parameters influencing the(pathophysiology and outcomes in alcoholic hepatitis (AH) patients. [Time frame: day-0 and day-7])
- Validation of identified transcriptomic and proteomic signatures associated with prognosis in(alcoholic hepatitis (AH) patients. [Time frame: day-0 and day-7])
研究者
研究点 (1)
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