Ignite Creation Date:
2024-05-06 @ 8:27 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06389851
Status:
RECRUITING
Last Update Posted:
2024-06-12
First Post:
2024-04-17
Brief Title:
Effects of Tomato Consumption on Steatosis Intestinal Function and Glucose and Lipid Metabolism in Subjects With NAFLD
Sponsor:
Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
Organization:
Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
Study Overview
Official Title:
Evaluation of the Effects of Tomato Consumption on the Parameters of Hepatic Steatosis Intestinal Function and on Glucose and Lipid Metabolism in Subjects With NAFLD
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The study in question is an interventional study with nutritional intervention the aim of the study is to evaluate whether a diet enriched with tomatoes can have favorable effects on
specific aspects associated with NAFLD such as the degree of hepatic steatosis and fibrosis
circulating levels of molecules correlated with the degree of generalized and hepatic inflammation and the blood concentrations of metabolic and cardiovascular risk factors associated with abdominal obesity
intestinal barrier
body composition
intestinal microbiota
symptoms of IBS irritable bowel syndrome in patients with NAFLD
specific aspects associated with NAFLD such as the degree of hepatic steatosis and fibrosis
circulating levels of molecules correlated with the degree of generalized and hepatic inflammation and the blood concentrations of metabolic and cardiovascular risk factors associated with abdominal obesity
intestinal barrier
body composition
intestinal microbiota
symptoms of IBS irritable bowel syndrome in patients with NAFLD
Detailed Description:
Chronic liver diseases are among the leading causes of morbidity mortality The increase in mortality from liver disease has been associated with the greater prevalence of NAFLD which is the most frequent chronic liver disease observed in clinical practice in Western countries The term hepatic steatosis is the hallmark of NAFLD and refers to a fat deposit in the liver cells greater than 5 and which is not related to alcohol intake or viral infections or the use of drugs It is possible to distinguish between hepatic steatosis and non-alcoholic steatohepatitis NASH a subtype of NAFLD in which fat deposition is associated with lobular inflammation with or without fibrosis characterized by the risk of possible progression to liver cirrhosis and possibly to hepatocellular carcinoma Hepatic steatosis is an independent risk factor for all liver alterations that characterize NAFLD particularly inflammation and fibrosis Globally the prevalence of NAFLD assessed by liver ultrasound is on average 3069 In the last 10-15 years its prevalence always assessed by liver ultrasound has increased by 387 going from 2516 in the period 1990-2006 to 3459 in the period 2016 -2019 If the highest prevalence of NAFLD is in Latin America 4437 it is 312 in North America and 251 in Western Europe Studies conducted in Italy indicate a prevalence of NAFLD of 225 -270 in the general population with a 2 prevalence of fibrosis diagnosed by non-invasive means In patients with NAFLD the mortality rate for all causes is equal to 1260 per 1000 person-years while that from cardiovascular causes extra-hepatic tumors and liver-related causes is respectively equal to 420 per 1000 peopleyear283 per 1000 person-years and 092 per 1000 person-years In the onset and progression of NAFLD alongside the role of insulin resistance and generalized inflammation pathways of relationship between the intestine and the liver are also involved in turn influenced by the type of intestinal microbiota Age also influences the evolution of these liver diseases and as they advance the prevalence of NAFLD and related fibrosis increases Furthermore the prevalence of NAFLD increases in parallel with the increase in the presence of metabolic alterations such as dyslipidemia and type 2 diabetes mellitus Al though the main causes of death in people affected by NAFLD are cardiovascular diseases and extrahepatic malignancies fibrosis hepatic advanced appears to be in itself an unfavorable prognostic marker for the outcomes of liver diseases In the absence of officially approved pharmacological therapies for the treatment of NAFLD European clinical guidelines and systematic reviews with meta-analyses recommend lifestyle-based interventions These mainly involve quantitative and qualitative changes in diet and an increase in regular physical exercise considered together as the best therapeutic strategy for the management of patients with NAFLD Diet can improve NAFLD by reducing the amount of liver fat and insulin resistance while exercise promotes weight loss and improves liver function The diet therefore acts as an effective prevention tool in combating metabolic-related diseases such as NAFLD In particular fruit with its high content of polyphenols has been shown to exert a high anti-inflammatory antithrombotic and antiproliferative action Recently it has been demonstrated in vitro on human colorectal carcinoma cell lines that table grape polyphenolic extracts can inhibit cell proliferation and growth as well as influence the morphology of the cell inhibiting its migration capacity These data support the idea that grapes as a nutraceutical can have health effects and prevent the mechanisms of oxidation cellular inflammation and metastasis Furthermore a clinical trial on healthy volunteers demonstrated that the daily intake of grapes can down-regulate the expression of small single-stranded non-coding RNA molecules called miRNAs metabolically associated with the metabolism of cancer of the gastrointestinal tract Therefore their inhibition would lead to preventing the transformation of the cell in a neoplastic sense Recently among food antioxidants particular attention has been paid to lycopene a phytochemical belonging to the carotenoid family Lycopene is found abundantly in vegetables and is responsible for their characteristic color Its bioactive properties are influenced by many factors such as bioavailability metabolism and interaction with other carotenoids In nature lycopene occurs in its trans isoform which is responsible for its bioavailability in the presence of elevated temperatures trans to cis It is assumed that due to the cis form lycopene is more highly bioavailable Since it is a fat-soluble substance the associated consumption of dietary fats amplifies its bioavailability The main sources of lycopene in the Mediterranean diet are tomatoes and tomato products In the European population lycopene consumption varies between 5 and 7 mgday and over 80 of its daily intake comes from tomato-based products Several studies have demonstrated the beneficial effects of lycopene on health resulting from its structure and lipophilic nature which determines its anti-inflammatory and antioxidant effects Recent studies suggest that changes in the intestinal microbiota may represent a new strategy to prevent or treat NAFLD and it is now known that a specific diet and regular physical exercise can induce changes in the composition of the intestinal microbiota which in turn contribute to an increase of insulin sensitivity and hepatic lipid metabolism Furthermore a recent prospective study observed that NAFLD is associated with an increase in 20 risk of developing irritable bowel syndrome IBS a disease not due to organic lesions and characterized by abdominal pain and abdominal swelling associated with frequent diarrhea or prolonged constipation often in periodic alternation relief of symptoms after defecation modification of the frequency of bowel movements andor consistency of the stool IBS affects 41 to 101 of the general population and is responsible for a reduction in the quality of life and an increase in healthcare costs and therefore it is a priority to identify lifestyle factors that can improve the IBS symptomsSince NAFLD and IBS share variations in circulating levels of proinflammatory cytokinesincreased tumor necrosis factor TNF-α interleukin IL-6 etc and reduction in IL-10cross-talk between the liver- brain-gut and gut-liver axis dysfunction of the intestinal microbiota alterations of the intestinal barrier and alterations of intestinal motility it cannot be excluded that the improvement or worsening of NAFLD may favor the improvement or worsening of IBS Furthermore it has been seen that the mechanisms that regulate intestinal barrier function are altered in NAFLD and this situation represents an aggravating factor Inflammation associated with liver disease may in turn play a significant role in the development of gastrointestinal GI disorders It is a chronic low intensity state that involves the entire organism Inflammation is related to an increase in inflammatory cytokines in tissues whichby activating immune responses alter cellular metabolic pathways In general chronic low-level inflammation and the variation in the concentration of metabolic hormones together with the distribution of adipose tissue in the abdominal cavity and alterations in the bacterial populations of the intestinal microbiota represent the main factors involved in the development of gastrointestinal pathologies that they develop precisely through alterations of the intestinal barrier The intestinal barrier can be considered a dynamic system that also responds to humoral signals and to a series of different molecules which in various ways are called into question Among these it is important to consider zonulin a GI peptide capable of modulating the functionality of tight junctions TJs Serum zonulin levels have been shown to correlate with the extent of mucosal barrier impairment Cellular andor TJ damage can have a significant impact on the correct function of intestinal permeability PI The I-FABPs intestinal fatty acid binding proteins are cytosolic proteins present in epithelial cells responsible for the transport of fatty acids They can be released into the circulation following the loss of membrane integrity and are rapidly eliminated in the urine therefore they represent non-invasive markers of early damage at the cellular level of the intestinal epithelium Likewise the heck oxidase DAO an intracellular enzyme with a high level of activity in the upper layer of the intestinal villi is considered a serum marker of intestinal epithelial integrity Alterations in the barrier function can favor the entry of bacteria and their products Lipopolysaccharide LPS a predominant component in the cell wall of Gram-negative bacteria has been found to influence barrier function Under physiological conditions LPS is unable to cross intact epithelium but in the presence of reduced epithelial integrity it can cross the GI barrier Tryptophan is an essential amino acid for humans since it is not synthesized in humans commensal bacteria catabolize tryptophan into various derivatives which are absorbed by the intestine and eliminated in the urine Two of these compounds indoxyl sulfate and 3-methyl-indole skatole are currently used to diagnose small intestinal and colon dysbiosis
The study will be a randomized and controlled study with nutritional intervention 60 subjects suffering from NAFLD will be enrolled and randomly assigned to the two groups of the study
Group A Treatment the subjects enrolled in this group will have to consume 200g of fresh raw tomatoes and 50g of sauce per day Group B Control the subjects enrolled in this group must comply with one diet free of tomatoes All groups will be provided with instructions on the diet to follow depending on the arm to which they will be assigned The treatment will last 6 weeks and in addition to the V0 Screening Visit 2 other visits V1-V2 are planned
At V0 will be subjected to Medical history Fibroscan to evaluate the degree of NAFLD - Detection of anthropometric characteristics BIA Test
Enrolled patients will be invited to return for V1 after 7 days to receive the personalized diet In V1 they will be subjected to blood sampling and body composition assessment using DEXA Whole blood and serum samples will be used for the measurement of routine blood chemistry parameters and nutritional metabolic and cardiovascular risk parameters The HOMA index and the degree of hepatic steatosis FLI and FIB-4 will be calculated The main adipokines leptin RBP-4 visfatin the main hepatic growth factors HGF Fetuin-A FGF21 FGF19 PAI-1 and the main proinflammatory cytokines highly sensitive C-reactive protein IL-6 IL-8 TNF-α and anti-inflammatory IL-4 other aliquots will be used for lipidomics and biochemical analyses On the serum samples taken from the subjects at times V1 and V2 the antioxidant activity and the inflammatory state and the serum levels of the deglycant enzymes will be evaluated through the study of the SOD1 and SOD2 enzymes IL-6 TNF-alpha and the Fructosamine 3-Kinase and glyoxalase The study subjects will also be asked to bring two stool samples for the evaluation of the intestinal microbiota and for the measurement of fecal Zonulin and the fecal metabolome as well as two urine samples
Optional visits Patients enrolled in the study will be asked on an optional and voluntary basis to undergo two outpatient sigmoidoscopies with cold biopsies if they wish to undergo
A sigmoidoscopy after the screening visit the second would be performed at the end of 6 weeks
The study will be a randomized and controlled study with nutritional intervention 60 subjects suffering from NAFLD will be enrolled and randomly assigned to the two groups of the study
Group A Treatment the subjects enrolled in this group will have to consume 200g of fresh raw tomatoes and 50g of sauce per day Group B Control the subjects enrolled in this group must comply with one diet free of tomatoes All groups will be provided with instructions on the diet to follow depending on the arm to which they will be assigned The treatment will last 6 weeks and in addition to the V0 Screening Visit 2 other visits V1-V2 are planned
At V0 will be subjected to Medical history Fibroscan to evaluate the degree of NAFLD - Detection of anthropometric characteristics BIA Test
Enrolled patients will be invited to return for V1 after 7 days to receive the personalized diet In V1 they will be subjected to blood sampling and body composition assessment using DEXA Whole blood and serum samples will be used for the measurement of routine blood chemistry parameters and nutritional metabolic and cardiovascular risk parameters The HOMA index and the degree of hepatic steatosis FLI and FIB-4 will be calculated The main adipokines leptin RBP-4 visfatin the main hepatic growth factors HGF Fetuin-A FGF21 FGF19 PAI-1 and the main proinflammatory cytokines highly sensitive C-reactive protein IL-6 IL-8 TNF-α and anti-inflammatory IL-4 other aliquots will be used for lipidomics and biochemical analyses On the serum samples taken from the subjects at times V1 and V2 the antioxidant activity and the inflammatory state and the serum levels of the deglycant enzymes will be evaluated through the study of the SOD1 and SOD2 enzymes IL-6 TNF-alpha and the Fructosamine 3-Kinase and glyoxalase The study subjects will also be asked to bring two stool samples for the evaluation of the intestinal microbiota and for the measurement of fecal Zonulin and the fecal metabolome as well as two urine samples
Optional visits Patients enrolled in the study will be asked on an optional and voluntary basis to undergo two outpatient sigmoidoscopies with cold biopsies if they wish to undergo
A sigmoidoscopy after the screening visit the second would be performed at the end of 6 weeks
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None