Clinical trial NCT05697991: Non-Alcoholic Fatty Liver Disease in a Saudi Cohort With Type 2 Diabetes Mellitus
Official title: Non-Alcoholic Fatty Liver Disease in a Saudi Cohort With Type 2 Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Nonalcoholic Fatty Liver Disease
Type 2 Diabetes Mellitus
Keywords: T2DM
Fatty Liver Disease
NAFLD
Lead sponsor: King Saud University
Sponsor class: OTHER
Collaborators: name: King Fahad Medical City
First posted: 2023-01-26
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population included patients who participated in the Cohort of Non-alcoholic Fatty Liver Disease with T2DM (the CORDIAL Study). This prospective cohort study started in 2015 and recruited patients from King Fahad Medical City (KFMC) and affiliated Primary Care Centers in Riyadh, Saudi Arabia. The patients will be prospectively followed up for 10 years for hepatic, metabolic, renal, and cardiovascular complications.

Brief summary: The global rise in the prevalence of obesity paved the way for the increased prevalence of yet another obesity-related complication significant enough to be considered within the roster of major public health threats: non-alcoholic fatty liver disease (NAFLD). In this follow-up study, the investigators will attempt to decipher the natural history of hepatic steatosis among patients with type 2 diabetes mellitus (T2DM) using state-of-the-art methods in a well-characterized Saudi cohort. The investigators aim also to validate existing biomarkers of disease severity and explore the pathogenesis of progressive disease using metabolic profiling technologies. A total of 1000 adult Saudi patients (males and females) with T2DM will be recruited. Those with co-morbidities, including hepatic decompensation, will be excluded. Participants will be followed three times for a total of 10 years/patient (Year 2, Year 5, and Year 10), and measures such as dietary evaluations, anthropometrics, and urine, stool, and blood examinations will be performed. Patients who develop NAFLD will be noted, and patterns/changes in the metabolic profile will be examined. For this specific grant (the first 2 years of the whole project), the investigators will be able to recruit the study cohort, do the baseline anthropometric, imaging, and biochemical measurements, and report the prevalence of NAFLD among patients with T2DM. This information will be the basis of subsequent follow-up and allow for validating potential diagnostic and prognostic biomarkers. This project will be of high importance at the national level since it will create awareness in the local medical community of the current severity status of NAFLD in the kingdom and will be used as a tool to promote public health awareness in the community.

Detailed description: The increased prevalence of obesity in both the developed and developing worlds paved the way to the increased prevalence of yet another obesity-related complication significant enough to be considered within the roster of major public health threats: non-alcoholic fatty liver disease (NAFLD). It has been estimated that approximately 20% to 30% of the adult population harbors NAFLD. It is also the most common liver pathology among children of developed countries. Unfortunately, despite the alarming figures, NAFLD remains largely underdiagnosed, probably because of its less aggressive nature and benign presentation compared with other liver diseases. Thus, it is apparent that NAFLD, being a precursor to more serious liver conditions such as cirrhosis and hepatocellular carcinoma, should be given equal, if not greater, clinical significance.

Accumulating evidence has pointed to parallel clinical similarities between NAFLD and metabolic syndrome (MetS), the clustering of cardiovascular risk factors with insulin resistance as the common unifying factor. It is well established that persons with MetS are at greater risk of progressing to major chronic non-communicable diseases such as coronary artery disease and type 2 diabetes mellitus (T2DM). Consequently, patients with T2DM are more likely to develop NAFLD. Obesity is acknowledged as one of the common denominators linking NAFLD, MetS, and T2DM, making dietary and lifestyle modifications the gold standard for the treatment of these clinical entities aside from pharmacotherapy that aims to improve insulin sensitivity. Therefore, it is important to better understand the intricate pathophysiology of NAFLD among patients with T2DM so that future interventions will be aimed at reversing complications.

Our current knowledge of NAFLD in terms of prognosis and treatment is promising yet inconclusive, which means that further investigations using prospective approaches are required. Only recently was a consensus design for clinical trials and endpoints for non-alcoholic steatohepatitis (NASH) reported. In this follow-up study, the investigators attempt to decipher the natural history of hepatic steatosis among patients with T2DM using state-of-the-art methods in a well-characterized Saudi cohort. Diabetes, and its related medical complications, have been identified as one of the priority areas of the National Plan for Science and Technology in the Kingdom of Saudi Arabia (KSA).

Eligibility criteria: Inclusion Criteria:

* Subject has provided informed consent prior to screening
* Men and women aged 18 to 60 years
* T2DM

Exclusion Criteria:

* Evidence of hepatic decompensation (ascites, clinical jaundice-bilirubin ≥ 40 µmol/L, encephalopathy)
* Preexisting hepatocellular carcinoma
* Other preexisting hepatic or extrahepatic malignancy
* Previous overt ischemic heart disease (myocardial infarction or acute coronary syndrome) or cerebrovascular disease (stroke or transient ischemic attack)
* Previous coronary artery bypass grafting, angioplasty, or stenting
* Any other issues that, in the opinion of the investigators, may preclude satisfactory completion of the study protocol

Primary outcomes:
measure: Prevalence of hepatic steatosis in T2DM
timeFrame: 15 years
Secondary outcomes:
measure: Progression of hepatic steatosis to advanced liver disease will be assessed by USS and FibroScan.
timeFrame: 15 years
measure: Pathogenesis of progressive disease
timeFrame: 15 years
Other outcomes:
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Fahad Medical City
state: Select A State Or Province
Study officials:
affiliation: King Saud University
name: Assim Alfadda, MD
role: PRINCIPAL_INVESTIGATOR
References: