An observational study in Metabolic Dysfunction-Associated Steatotic Liver Disease, Non Celiac Wheat Sensitivity and Irritable Bowel Syndrome, sponsored by University of Palermo. Recruiting at 2 sites in Italy. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-08-11.
Sponsored by University of Palermo · Observational
Hypothesizing an intestinal barrier impairment as a common pathophysiological substrate of both Non Celiac Wheat Sensitivity (NCWS) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MAFLD), in a retrospective cohort study (data not yet published), demographic, clinical, laboratory and histology data of NCWS patients at the time of diagnosis, were analyzed and compared to control subjects with Irritable Bowel Syndrome/Functional Dyspepsia (IBS/FD) and freshly diagnosed Celiac Disease (CeD). NCWS diagnosis was performed by a double-blind placebo-controlled wheat challenge. Steatosis was confirmed by ultrasound examination. Our retrospective data showed that the frequency of liver of steatosis was lower in NCWS than in IBS patients. In addition, it seems that pre-diagnosis avoidance of wheat in NCWS correlates with protection from steatosis. A subset of NCWS patients, recently exposed to wheat, with clinical features suggesting increased IP, seems to be predisposed to liver steatosis and fibrosis.
To validate the results of the retrospective study, the researchers planned the present prospective study, to analyze the prevalence of liver steatosis and fibrosis, evaluated by ultrasound (US) examination, FibroScan analysis [CAP (Controlled Attenuation Parameter) and LSM (Liver Stiffness Measurement) values], FIB-4 (Fibrosis-4) index, and NFS [Non-alcoholic fatty liver disease (NAFLD) Fibrosis Score], in patients with NCWS at the time of diagnosis, comparing them with two control populations of newly diagnosed IBS/FD and CeD patients.
Many people with symptoms similar to inflammatory bowel syndrome (IBS) or functional dyspepsia (FD) follow a wheat-free diet (WFD) because it is subjectively better tolerated, even if they do not suffer from celiac disease (CeD) or wheat allergy. This condition, originally named non-celiac gluten sensitivity, has been redefined as non-celiac wheat sensitivity (NCWS), because its clinical manifestations can be triggered by a spectrum of non-gluten wheat proteins, such as wheat amylase-trypsin inhibitors (ATIs), that cause a delayed type - non-IgE-mediated food allergy associated with an intestinal mucosa barrier (IB) defect.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease in countries with excess nutrient supply. In addition to the main etiopathogenetic factors, other factors must be implicated: nutrition, intestinal microbiota, intestinal permeability (IP) and the gut-liver axis might play a key role due to the translocation of nutrient-derived peptides and microbial products into the intestinal lamina propria. Here, the liver is prominently exposed to the inflammatory intestinal signals via the mesenteric-portal venous system, that significantly contributes to the onset of MASLD, metabolic disfunction-associated steatohepatitis (MASH) and liver fibrosis.
In patients with NCWS, intake of wheat and wheat ATIs (Amylase-Trypsin Inhibitors) increases IP, promotes intestinal dysbiosis, and activates the gastrointestinal and extra-intestinal immune response.
Hypothesizing an intestinal barrier impairment as a common pathophysiological substrate of both NCWS and MAFLD, in a retrospective cohort study (data not yet published), demographic, clinical, laboratory and histology data of NCWS patients at the time of diagnosis, were analyzed and compared to control subjects with IBS/FD and freshly diagnosed CeD. NCWS diagnosis was performed by a double-blind placebo-controlled wheat challenge. Steatosis was confirmed by ultrasound examination. Our retrospective data showed that the frequency of liver of steatosis was lower in NCWS than in IBS patients. In addition, it seems that pre-diagnosis avoidance of wheat in NCWS correlates with protection from steatosis. A subset of NCWS patients, recently exposed to wheat, with clinical features suggesting increased IP, seems to be predisposed to liver steatosis and fibrosis.
To validate the results of the retrospective study, the researchers planned the present prospective study, to analyze the prevalence of liver steatosis and fibrosis, evaluated by ultrasound examination, FibroScan analysis [CAP (Controlled Attenuation Parameter) and LSM (Liver Stiffness Measurement) values], FIB-4 (Fibrosis-4) index, and NFS [Non-alcoholic fatty liver disease (NAFLD) Fibrosis Score], in patients with NCWS at the time of diagnosis, comparing them with two control populations of newly diagnosed IBS/FD and CeD patients.
1,116 studies on the registry are indexed under Irritable Bowel Syndrome; 208 are open to participants now.
This study's planned enrollment of 250 is above the median of 160 across 191 observational studies indexed under Irritable Bowel Syndrome.
Browse Irritable Bowel Syndrome studies →University of Palermo is the lead sponsor of 145 studies on the registry; 28 are open to participants now.
Counted across the registry records on this site, refreshed daily.
This is a prospective multicenter study conducted on patients with Non-Celiac Wheat Sensitivity (NCWS), consecutively diagnosed by double-blind placebo-controlled challenge (DBPCC) with wheat, from January 2024, in the outpatient clinics of two Internal Medicine Units: University Hospital of Palermo, Italy, and "Villa-Sofia-Cervello" Hospital, Palermo, Italy. The records of the patients were prospectively collected and analyzed, together with those of two control populations of Irritable Bowel Syndrome/Functional Dyspepsia (IBS/FD) unrelated to food (including wheat) allergies/intolerances, and Celiac Disease (CeD), consecutively recruited in the same period and in the same outpatient clinics, before diagnosis (baseline) and after 1 year of follow-up.
The inclusion/exclusion criteria used to select the study population have been previously validated in other retrospective studies. Additional exclusion criteria related to steatosis and other liver diseases and specifically required for this study were adopted.
Inclusion criteria for Non-Celiac Wheat Sensitivity (NCWS) patients
Inclusion criteria for Irritable Bowel Syndrome/Functional Dyspepsia (IBS/FD) and other functional gastrointestinal disorders unrelated to NCWS or other food allergies/intolerances patients
Inclusion criteria for Celiac Disease (CeD) patients
Exclusion criteria for all the patients enrolled in the study
Additional exclusion criteria related to liver steatosis and other liver diseases
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Non-Celiac Wheat Sensitivity (NCWS) patients, consecutively diagnosed by double-blind placebo-controlled challenge (DBPCC) with wheat
Diagnostic Test: Prevalence and severity of liver steatosis and fibrosis,
Control population of Irritable Bowel Syndrome/Functional Dyspepsia (IBS/FD) patients unrelated to food (including wheat) allergies/intolerances
Diagnostic Test: Prevalence and severity of liver steatosis and fibrosis,
Control populations of Celiac Disease (CeD) patients
Diagnostic Test: Prevalence and severity of liver steatosis and fibrosis,
To establish the prevalence and severity of liver steatosis and fibrosis, the researchers will analyze data from the UltraSound (US) and FibroScan examinations, and from two validate scores performed before diagnosis.
Prevalence and severity of liver steatosis and fibrosis by Ultrasound examination
Steatosis was evaluated according to international validated Ultrasound (US) criteria and classified as follows: absent (score 0), when the echostructure of the liver was normal; mild (score 1), when there was a mild, diffuse increase in hepatic echogenicity, with normal visualization of the portal vein wall and diaphragm; moderate (score 2), in the case of a moderate increase in hepatic echogenicity, with a less clear/slightly altered demarcation of the portal vein wall and diaphragm; severe (score 3), in the case of markedly increased hepatic echogenicity, with little or no visualization of the portal vein wall, diaphragm and posterior part of the right hepatic lobe.
Time frame: At baseline, before diagnosis
Prevalence and severity of liver steatosis by FibroScan analysis
FibroScan analysis provides CAP (Controlled Attenuation Parameter, normal validated cut-offs of ≤275 dB/m) and LSM (Liver Stiffness Measurement, normal validated cut-offs of ≤5.5 kPa) values for liver steatosis and fibrosis, respectively. Detailed scores were, for CAP, Normal values ≤275 dB/m; Mild Steatosis (S1): 275-290 dB/m; Moderate Steatosis (S2): 290-302 dB/m; Severe Steatosis (S3): ≥302 dB/m. For LSM, F0 (No fibrosis): ≤5.5-6.0 kPa; F1 (Mild fibrosis): 5.6-7.0 kPa; F2 (Moderate/significant fibrosis): 7.1-9.4 kPa; F3 (Severe/Advanced fibrosis): 9.5-14.5 kPa; F4 (Cirrhosis): ≥14.6 kPa.
Time frame: At baseline, before diagnosis
Prevalence and severity of liver steatosis and fibrosis by FIB-4
A validated score was used to assess the risk for significant liver fibrosis in MASLD: the FIB-4 index. Based on this test, our cohort was stratified as being at low- or moderate-high-risk for advanced fibrosis, based on validated cut-off of ≤1.3 for a low-risk and of ≥1.4 for moderate-high-risk.
Time frame: At baseline, before diagnosis
Prevalence and severity of liver steatosis and fibrosis by NFS
Another validated score was used to assess the risk for significant liver fibrosis in MASLD: the NFS. Based on this test, our cohort was stratified as being at low- or moderate-high-risk for advanced fibrosis, based on validated cut-off ≤1.455 for NFS for a low-risk and of ≥1.456 for moderate-high-risk.
Time frame: At baseline, before diagnosis
Plan to share: No
Started Jan 2024 (actual). Primary completion is estimated for Dec 2028, 59 months after the start.
Of 51 non-industry observational studies under Irritable Bowel Syndrome, half reached primary completion within 53 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 193. This study's planned 59 months is above that.
Counting every sponsor, half of 65 studies reached it within 40 months; a quarter within 21 and three quarters within 109.
How these figures are worked out, and which studies are left out of them.
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