| CTRI Number |
CTRI/2023/01/048844 [Registered on: 09/01/2023] Trial Registered Prospectively |
| Last Modified On: |
09/01/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Observational |
|
Type of Study
|
Cohort Study |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
Proteomic and transcriptomic analysis to understand the biology of alcoholic hepatitis
|
|
Scientific Title of Study
|
Integrated multi-omics and machine learning to decipher pathobiology and
outcomes in alcoholic hepatitis patients |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Nipun Verma |
| Designation |
Associate Professor |
| Affiliation |
PGIMER, CHandigarh |
| Address |
Department of Hepatology, Nehru Hospital Extension Block, PGIMER, Sector-12, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9914208562 |
| Fax |
|
| Email |
nipun29j@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Nipun Verma |
| Designation |
Associate Professor |
| Affiliation |
PGIMER, CHandigarh |
| Address |
Department of Hepatology, Nehru Hospital Extension Block, PGIMER, Sector-12, Chandigarh
CHANDIGARH
160012
India |
| Phone |
9914208562 |
| Fax |
|
| Email |
nipun29j@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Nipun Verma |
| Designation |
Associate Professor |
| Affiliation |
PGIMER, CHandigarh |
| Address |
Department of Hepatology, Nehru Hospital Extension Block, PGIMER, Sector-12, Chandigarh
CHANDIGARH
160012
India |
| Phone |
9914208562 |
| Fax |
|
| Email |
nipun29j@gmail.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
ICMR |
| Address |
ICMR, V. Ramalingaswami Bhawan, P.O. Box No. 4911. Ansari Nagar, New Delhi - 110029, India. |
| Type of Sponsor |
Government funding agency |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Nipun Verma |
PGIMER, Chandigarh |
Department of Hepatology, Nehru Hospital Extension block, PGIMER, Chandigarh
Chandigarh
CHANDIGARH |
9914208562
nipun29j@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| PGIMER Institutional Ethics committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K74||Fibrosis and cirrhosis of liver, |
|
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Intervention / Comparator Agent
|
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1. Patients age 18 to 80 years
2. 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 |
|
| ExclusionCriteria |
| Details |
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 |
|
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Method of Generating Random Sequence
|
|
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Method of Concealment
|
|
|
Blinding/Masking
|
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Primary Outcome
|
| Outcome |
TimePoints |
| Impact of GH along with standard medical therapy (SMT) as compared to SMT-alone on overall survival (Time frame 30 days) |
30 days and 90 days |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
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] |
0-16 months |
Proteomic analysis of neutrophils towards unravelling parameters influencing the
pathophysiology and outcomes in alcoholic hepatitis (AH) patients. [Time frame: day-0 and day-7] |
0-16 months |
Validation of identified transcriptomic and proteomic signatures associated with prognosis in
alcoholic hepatitis (AH) patients. [Time frame: day-0 and day-7] |
18-34 months |
|
|
Target Sample Size
|
Total Sample Size="150"
Sample Size from India="150"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
15/01/2023 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
- 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.
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