Evaluation of Gut Permeability in Patients Affected by Obesity and NAFLD: Influence of Ketogenic Diet.

Evaluation of Gut Permeability in Patients Affected by Obesity and NAFLD: Influence of Ketogenic Diet on Diagnostic and Prognostic Markers in Liver Disease

This study is open label, with one arm only. In this study will be enrolled patients with obesity (BMI more than 30). Aim of the study is to determine the influence (if any) of a very low calorie ketogenic diet (VLCKD) on gut permeability and liver steatosis.

The first objective is to examine the influence of obesity on the prevalence and severity of impaired intestinal permeability and hepatic steatosis.

Intestinal permeability means the ability of the intestinal barrier to block the passage of substances potentially harmful to our body.

The second objective is to evaluate whether a low-calorie and ketogenic dietary intervention, lasting 6 weeks, can change intestinal permeability and hepatic steatosis

Study Overview

• Status: Recruiting
• Conditions: Obesity; NAFLD; Permeability; Increased
• Intervention / Treatment: Dietary supplement: Ketogenic Diet

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giovanni De Perogla, Prof; Phone Number: 0804994635; Email: giovanni.depergola@irccsdebellis.it

Study Locations

• Italy
  • Bari
    • Castellana Grotte, Bari, Italy, 70013
      • Recruiting
      • Irccs Saverio de Bellis
      • Contact: Giovanni De Pergola, Professor; Phone Number: 0804994635; Email: giovanni.depergola@irccsdebellis.it
      • Contact: Sara De Nucci, Dr; Phone Number: 0804994635; Email: sa.denucci@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. BMI ≥ 30 Kg/m2 or abdominal circumference (waist) >94 cm in men and >80 cm in women (IDF criteria for the definition of abdominal obesity) with or without the features that characterize the metabolic syndrome
2. Age range between 18 and 70 years, both sexes
3. Diagnosis of hepatic steatosis, formulated on the basis of fibroscan [CAP (controlled attenuation parameter) > 238 dB/m(decibel/meter)], and other recognized criteria (FLI - Fatty Liver Index , FIB-4 - Fibrosis-4 index, NFS - NAFLD fibrosis score).

Exclusion Criteria:

1. Normal and underweight subjects
2. Presence of any pathology that may affect the presence of altered intestinal permeability or steatosis, apart from pathologies that represent inclusion criteria
3. Treatment with any device, pharmacological or not, that can affect intestinal permeability and liver metabolism and, therefore, the presence of steatosis
4. Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intervention arm with VLCKD; all patients will receive a very low calorie Ketogenic diet (VLCKD) and will be followed for all the time of the study, monitoring gut permeability, liver steatosis and microbiome composition	Dietary supplement: Ketogenic Diet; all patients will receive a very low calorie ketogenic diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut permeability	examine the influence of obesity on possible alterations (if any) in intestinal permeability. subjects drank a sugar test solution containing 10 g of lactulose, 5 g of mannitol, and 40 g of sucrose in a volume of 100 ml. Urine samples were collected up to 5 h after administration. . Te percentage of ingested La (%La), Ma (%Ma), and Su (%Su) were evaluated in urine, and the La/Ma ratio was calculated for each sample. Patients with a La/Ma ratio higher than 0.030 were considered as having an altered gut permeability	6 weeks
Gut Dysbiosis	evaluate the impact of the low-calorie and ketogenic diet on possible alterations of the intestinal microbiome. The dysbiosis test is based on urinary quantification of two metabolites deriving from the decomposition of tryptophan, skatole (3-methyl-indole), and indican. Urinary indican and skatole were considered normal at values lower than 10 mg/L and 10 µg/L, respectively. Urinary concentrations of indican and skatole higher than 20 mg/L and 20 µg/L indicate the presence of fermentative and putrefactive grade I dysbiosis, respectively	6 weeks

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
• Collaborators: Francesco Russo; Giuseppe, Riezzo; Michele, Linsalata; Antonella, Orlando; Benedetta, D Attoma; Laura, Prospero; Antonia, Ignazzi; Sara, De Nucci; Raffaele, Cozzolongo; Vito, Giannuzzi; Maria, De Angelis; Giusy Rita, Caponio; Oronzo, Milella; Gianluigi, Giannelli
• Investigators: Principal Investigator: Giovanni De Pergola, Prof, IRCCS "Saverio De Bellis"

Publications and helpful links

General Publications

• Genser L, Aguanno D, Soula HA, Dong L, Trystram L, Assmann K, Salem JE, Vaillant JC, Oppert JM, Laugerette F, Michalski MC, Wind P, Rousset M, Brot-Laroche E, Leturque A, Clement K, Thenet S, Poitou C. Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes. J Pathol. 2018 Oct;246(2):217-230. doi: 10.1002/path.5134. Epub 2018 Aug 28.
• Damms-Machado A, Louis S, Schnitzer A, Volynets V, Rings A, Basrai M, Bischoff SC. Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction. Am J Clin Nutr. 2017 Jan;105(1):127-135. doi: 10.3945/ajcn.116.131110. Epub 2016 Nov 9.
• Mkumbuzi L, Mfengu MMO, Engwa GA, Sewani-Rusike CR. Insulin Resistance is Associated with Gut Permeability Without the Direct Influence of Obesity in Young Adults. Diabetes Metab Syndr Obes. 2020 Aug 24;13:2997-3008. doi: 10.2147/DMSO.S256864. eCollection 2020.
• Ott B, Skurk T, Hastreiter L, Lagkouvardos I, Fischer S, Buttner J, Kellerer T, Clavel T, Rychlik M, Haller D, Hauner H. Effect of caloric restriction on gut permeability, inflammation markers, and fecal microbiota in obese women. Sci Rep. 2017 Sep 20;7(1):11955. doi: 10.1038/s41598-017-12109-9.
• Muscogiuri G, El Ghoch M, Colao A, Hassapidou M, Yumuk V, Busetto L; Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO). European Guidelines for Obesity Management in Adults with a Very Low-Calorie Ketogenic Diet: A Systematic Review and Meta-Analysis. Obes Facts. 2021;14(2):222-245. doi: 10.1159/000515381. Epub 2021 Apr 21.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2022
• Primary Completion (Actual): May 28, 2024
• Study Completion (Estimated): May 28, 2025

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: July 25, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: obesity; NAFLD; Gut permeability; Ketogenic diet
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Fatty Liver; Obesity; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: NAFLDdietachetogenica

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No