Integrated Multi-omics Data for Personalized Treatment of Obesity-associated Fatty Liver Disease

Sponsor

Institut Investigacio Sanitaria Pere Virgili (Other)

Overall Status

Recruiting

CT.gov ID

NCT05554224

Collaborator

Hospital Universitari Sant Joan (Other), University of Barcelona (Other), La Caixa Foundation (Other), Instituto de Salud Carlos III (Other)

2,000

Enrollment

Location

246.2

Anticipated Duration (Months)

8.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators seek to analyze the samples provided by patients with obesity-associated fatty liver disease at the multi-omics level and to integrate the results with clinical information, genotypic variants, and factors influencing inter-organ crosstalk. The main aim is to improve the interpretation of fatty liver disease associated with obesity and diabetes by developing predictive models built with algorithms from artificial intelligence. The challenge is to decipher the flow of information by exploring contributing factors, proximate causes of regulatory defects, and maladaptive responses that may promote therapeutic approaches.

Condition or Disease	Intervention/Treatment	Phase
NAFLD Obesity, Morbid Comorbidities and Coexisting Conditions	Diagnostic Test: To propose diagnostic tests for liver diseases before surgical decisions.

Detailed Description

The investigators study the most prevalent liver disease in the history of humankind, which is the leading cause of liver transplantation in its severe forms. It results from two silent pandemics with enormous health impacts: obesity and diabetes. Together or separately, they affect more than 30% of the world's population. The current term for the disease is MAFLD (metabolic (dysfunction)-associated fatty liver disease). This designation indicates that metabolic disorders related to obesity, diabetes, dyslipidemia, and hypertension are its primary cause. These disorders are related and lead to fat accumulation in the liver, the first step in a broad spectrum of chronic liver diseases. These diseases respond clinically in a very variable way and remain undiagnosed and untreated for a long time. There is no accepted pharmacological treatment, and lifestyle changes, although possibly effective, usually fail because they require particularly favorable conditions. Therefore, the identified problems that should be solve are:

(1) The diagnosis of MAFLD requires a liver biopsy, a costly and aggressive procedure. (2) Without examining the liver, clinicians can know little about the progression of the disease and the underlying causes. (3) The results in experimental models can be informative but difficult to translate to the clinic. Recent reports suggest the essential role of phospholipid biosynthesis and transport between the endoplasmic reticulum and mitochondria. (4) All of the above makes it difficult to obtain the necessary information to propose changes in clinical guidelines.

Considering these aspects, patients with morbid obesity can be an informative human model. Among other advantages, patients have surgical options that allow us to obtain portions of affected organs that facilitate specific diagnosis and that, because they require constant care, can be studied on an ongoing basis. The presented approach can improve patient care and essentially consists of identifying the most significant number of variables that can help. In particular, here are proposed the inclusion of variables that can already be obtained from recent advances in the laboratory, encompassed within the omics sciences (genomics, transcriptomics, proteomics, metabolomics, lipidomics, microbiomics). Each of these has its advantages and limitations. Predictive models can integrate these variables into clinical data to explore organ crosstalk.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

2000 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Integrated Multi-omics and Machine Learning-driven Personalized Treatment of Obesity-associated Fatty Liver Disease

Actual Study Start Date :

Jun 25, 2008

Anticipated Primary Completion Date :

Dec 31, 2028

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Severe obesity without liver disease Patients with severe obesity who did not meet the criteria described in Kleiner et al. (2005) for nonalcoholic steatohepatitis diagnosis (score 0-2).	Diagnostic Test: To propose diagnostic tests for liver diseases before surgical decisions. Observational although patients are candidates for metabolic surgery. Other Names: External follow up monitoring liver diseases and weight loss.
Severe obesity with liver disease without criteria for steatohepatitis Patients with severe obesity who did not meet the criteria described in Kleiner et al. (2005) for nonalcoholic steatohepatitis diagnosis, but their biopsies presented some liver severity (scores 3 and 4).	Diagnostic Test: To propose diagnostic tests for liver diseases before surgical decisions. Observational although patients are candidates for metabolic surgery. Other Names: External follow up monitoring liver diseases and weight loss.
Severe obesity with well-defined steatohepatitis and/or cirrhosis Patients with severe obesity who met the criteria described in Kleiner et al. (2005) for nonalcoholic steatohepatitis diagnosis (score 5-8).	Diagnostic Test: To propose diagnostic tests for liver diseases before surgical decisions. Observational although patients are candidates for metabolic surgery. Other Names: External follow up monitoring liver diseases and weight loss.

Arm

Intervention/Treatment

Severe obesity without liver disease

Patients with severe obesity who did not meet the criteria described in Kleiner et al. (2005) for nonalcoholic steatohepatitis diagnosis (score 0-2).

Diagnostic Test: To propose diagnostic tests for liver diseases before surgical decisions.

Observational although patients are candidates for metabolic surgery.

Other Names:

External follow up monitoring liver diseases and weight loss.

Severe obesity with liver disease without criteria for steatohepatitis

Patients with severe obesity who did not meet the criteria described in Kleiner et al. (2005) for nonalcoholic steatohepatitis diagnosis, but their biopsies presented some liver severity (scores 3 and 4).

Diagnostic Test: To propose diagnostic tests for liver diseases before surgical decisions.

Observational although patients are candidates for metabolic surgery.

Other Names:

External follow up monitoring liver diseases and weight loss.

Severe obesity with well-defined steatohepatitis and/or cirrhosis

Patients with severe obesity who met the criteria described in Kleiner et al. (2005) for nonalcoholic steatohepatitis diagnosis (score 5-8).

Diagnostic Test: To propose diagnostic tests for liver diseases before surgical decisions.

Observational although patients are candidates for metabolic surgery.

Other Names:

External follow up monitoring liver diseases and weight loss.

Outcome Measures

Primary Outcome Measures

Weight change [1 to 10 years]
The effect of bariatric surgery on adiposity outcomes.
Type 2 diabetes mellitus incidence [1 to 10 years]
The effect of bariatric surgery on metabolic outcomes.
Hypertension incidence [1 to 10 years]
The effect of bariatric surgery on metabolic outcomes.
Chronic liver diseases incidence [1 to 10 years]
The usefulness of imaging techniques on metabolic outcomes.
Dyslipidemia incidence [1 to 10 years]
The effect of bariatric surgery on metabolic outcomes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Body mass index greater or equal to 40 kg/m^2.
Body mass index between 35 and 40 kg/m^2 with high-risk comorbidities (diagnosis or treatment for hypertension, dyslipidemia, or type 2 diabetes mellitus).
Positive psychiatric evaluation.
Age greater or equal to 18 years old.