Impact of a Low-FODMAP Gluten-free Diet on Gut Microbiota and Circulating miRNAs in Celiac Disease Patients (FODMAP2019)
Primary Purpose
Celiac Disease
Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Low FODMAPs /balanced gluten free diet
Sponsored by
About this trial
This is an interventional treatment trial for Celiac Disease focused on measuring FODMAPs diet, celiac disease, microbiota, miRNA
Eligibility Criteria
Inclusion Criteria:
- patients on a proper gluten-free diet (assessing adherence to the gluten-free diet using the Celiac Dietary Adherence Test (CDAT)
- celiac subjects diagnosed through a positive serological test of anti-endomysium antibodies (EMA) and tissue transglutaminase antibodies (TTG) evaluated through a histological abnormality in duodenal biopsies in accordance with Marsh's modified classification
- refractory celiac disease (CD)
Exclusion Criteria:
- Women who are pregnant or breastfeeding
- Subjects who follow special diets: vegetarianism, veganism
- Subjects with psychiatric disorders, diabetes mellitus, autoimmune systemic diseases, previous anaphylactic episodes, systemic disorders
- individual intolerance to disaccharides evaluated through the expired hydrogen test (lactose and fructose)
Sites / Locations
- Leda RoncoroniRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Low FODMAPs /balanced gluten free diet
Balanced gluten free diet
Arm Description
Dietary Supplement: Balanced low FODMAPs /gluten free diet. An expert in nutrition will give a balanced gluten free diet to patients, low in FODMAPs foods.
Balanced gluten free diet. An expert in nutrition will give a balanced gluten free diet to patients.
Outcomes
Primary Outcome Measures
Microbiota alpha and beta diversity
Evaluate both the biodiversity and the relative abundance of haematic, intestinal and duodenal bacteria in the refractory celiac population of type I and II compared to normoresponsive celiac patients
Secondary Outcome Measures
miRNAs
Evaluate the regulation of duodenal miRNAs in RCD patients and compare them with the miRNAs expressed in normoresponsive patients
IBS symptoms
Improvement of VAS values of IBS symptoms in patients undergoing a balanced Gluten Free/low FODMAPs diet compared to patients undergoing only a balanced. Evaluated IBS symptoms are: abdominal pain, bloating, satisfaction with stool consistency, epigastric pain, postprandial fullness, early satiety.
SF-36
Improvement of quality of life assessed through SF-36 questionnaire (eight scale scores) in patients undergoing a balanced Gluten Free/low FODMAPs diet compared to patients undergoing only a balanced gluten free diet.
SCL 90
Improvement of psychological problems and symptoms of psychopathology through the symptom checklist 90 R (SCL 90 R) in patients undergoing a balanced Gluten Free/low FODMAPs diet compared to patients undergoing only a balanced gluten free diet
Dietary intake
Evaluation of the dietary intake in micro and macro-nutrients before and after following the assigned diet through questionnaire.
Full Information
NCT ID
NCT04655495
First Posted
November 17, 2020
Last Updated
January 16, 2023
Sponsor
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
1. Study Identification
Unique Protocol Identification Number
NCT04655495
Brief Title
Impact of a Low-FODMAP Gluten-free Diet on Gut Microbiota and Circulating miRNAs in Celiac Disease Patients
Acronym
FODMAP2019
Official Title
Impact of a Low-FODMAP Gluten-free Diet on Gut Microbiota and Circulating miRNAs in Different Phenotypes of Celiac Disease Patients
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 6, 2022 (Actual)
Primary Completion Date
January 9, 2023 (Actual)
Study Completion Date
January 9, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
15 patients with refractory celiac disease (RCD) and 15 patients with CD responsive to the GFD between the ages of 21 and 60 will be enrolled. The aim of the research will be: 1) to characterize the intestinal, blood and duodenal microbiota, then to evaluate both the taxonomy of the identified bacteria and their relative abundance 2) to analyse the profile of miRNAs from biopsy and fibroblasts isolated in the first duodenal portion, highlighting any basal deregulation and, for fibroblasts, after treatment with the 33-mer immunogenic peptide 3) quantify and know the composition of the fecal microbiota in celiac patients with persistent symptoms and in refractory celiac patients before (T0) and after (T28) treatment with a low-FODMAP diet. The aim of the study is to observe a diversification of the microbiota pattern of refractory patients vs. normoresponsive celiac patients and to observe a deregulation in the expression of miRNAs, both basally on biopsies and after treatment with the immunogenic peptide in primary fibroblast cultures.
Detailed Description
Celiac disease (CD) is a chronic, autoimmune, multisystemic disorder caused by ingestion of gluten contained in wheat. A chronic gluten-free diet (GFD) is the only therapy for CD, however a small subgroup of patients is refractory to a GFD, in fact the pathology does not regress even with a strict diet. The microbiota plays a fundamental role in the CD, in fact, especially intestinal homeostasis requires balanced interactions between the microbiota, food antigens and the host. It is widely recognized that intestinal microbiota plays a role in the initiation and progression of intestinal inflammation in numerous chronic conditions, but recent studies have shown that even the blood microbiota plays a fundamental role in autoimmune diseases. Also microRNAs (miRNAs), RNA sequences of 20-22 non-coding nucleotides that post-transcriptionally regulate gene expression, are molecules of interest in many common diseases and therefore also in CD. Fermentable, Oligo-, Di-, Mono-saccharides And Polyol (FODMAP) are short-chain carbohydrates with poor absorption in the small intestine which increases gas production and intestinal osmolarity, which can trigger gastrointestinal symptoms in sensitive individuals. A diet low in FODMAPs is a new dietary option for the treatment of persistent gastrointestinal symptoms in celiac patients. Evaluating the effect of this type of diet on intestinal microbiota changes and miRNA expression in celiac patients with persistent gastroenterological symptoms and in patients with refractory celiac disease represents an opportunity to understand how this dietary modification could contribute to the development of this disease.
15 patients with refractory celiac disease (RCD) and 15 patients with CD responsive to the GFD between the ages of 21 and 60 will be enrolled. The aim of the research will be: 1) to characterize the intestinal, blood and duodenal microbiota, then to evaluate both the taxonomy of the identified bacteria and their relative abundance 2) to analyse the profile of miRNAs from biopsy and fibroblasts isolated in the first duodenal portion, highlighting any basal deregulation and, for fibroblasts, after treatment with the 33-mer immunogenic peptide 3) quantify and know the composition of the fecal microbiota in celiac patients with persistent symptoms and in refractory celiac patients before (T0) and after (T28) treatment with a low-FODMAP diet. The aim of the study is to observe a diversification of the microbiota pattern of refractory patients vs. normoresponsive celiac patients and to observe a deregulation in the expression of miRNAs, both basally on biopsies and after treatment with the immunogenic peptide in primary fibroblast cultures.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Celiac Disease
Keywords
FODMAPs diet, celiac disease, microbiota, miRNA
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Low FODMAPs /balanced gluten free diet
Arm Type
Experimental
Arm Description
Dietary Supplement: Balanced low FODMAPs /gluten free diet. An expert in nutrition will give a balanced gluten free diet to patients, low in FODMAPs foods.
Arm Title
Balanced gluten free diet
Arm Type
Active Comparator
Arm Description
Balanced gluten free diet. An expert in nutrition will give a balanced gluten free diet to patients.
Intervention Type
Dietary Supplement
Intervention Name(s)
Low FODMAPs /balanced gluten free diet
Intervention Description
Dietary Supplement: Balanced low FODMAPs /gluten free diet
Primary Outcome Measure Information:
Title
Microbiota alpha and beta diversity
Description
Evaluate both the biodiversity and the relative abundance of haematic, intestinal and duodenal bacteria in the refractory celiac population of type I and II compared to normoresponsive celiac patients
Time Frame
28 days
Secondary Outcome Measure Information:
Title
miRNAs
Description
Evaluate the regulation of duodenal miRNAs in RCD patients and compare them with the miRNAs expressed in normoresponsive patients
Time Frame
28 days
Title
IBS symptoms
Description
Improvement of VAS values of IBS symptoms in patients undergoing a balanced Gluten Free/low FODMAPs diet compared to patients undergoing only a balanced. Evaluated IBS symptoms are: abdominal pain, bloating, satisfaction with stool consistency, epigastric pain, postprandial fullness, early satiety.
Time Frame
28 days
Title
SF-36
Description
Improvement of quality of life assessed through SF-36 questionnaire (eight scale scores) in patients undergoing a balanced Gluten Free/low FODMAPs diet compared to patients undergoing only a balanced gluten free diet.
Time Frame
28 days
Title
SCL 90
Description
Improvement of psychological problems and symptoms of psychopathology through the symptom checklist 90 R (SCL 90 R) in patients undergoing a balanced Gluten Free/low FODMAPs diet compared to patients undergoing only a balanced gluten free diet
Time Frame
28 days
Title
Dietary intake
Description
Evaluation of the dietary intake in micro and macro-nutrients before and after following the assigned diet through questionnaire.
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
patients on a proper gluten-free diet (assessing adherence to the gluten-free diet using the Celiac Dietary Adherence Test (CDAT)
celiac subjects diagnosed through a positive serological test of anti-endomysium antibodies (EMA) and tissue transglutaminase antibodies (TTG) evaluated through a histological abnormality in duodenal biopsies in accordance with Marsh's modified classification
refractory celiac disease (CD)
Exclusion Criteria:
Women who are pregnant or breastfeeding
Subjects who follow special diets: vegetarianism, veganism
Subjects with psychiatric disorders, diabetes mellitus, autoimmune systemic diseases, previous anaphylactic episodes, systemic disorders
individual intolerance to disaccharides evaluated through the expired hydrogen test (lactose and fructose)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Leda Roncoroni, MS, PhD
Phone
+390255033384
Email
leda.roncoroni@unimi.it
Facility Information:
Facility Name
Leda Roncoroni
City
Milan
ZIP/Postal Code
20100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luca Elli, MD, PhD
First Name & Middle Initial & Last Name & Degree
Leda Roncoroni, MS, PhD
First Name & Middle Initial & Last Name & Degree
Alice Scricciolo, MS
First Name & Middle Initial & Last Name & Degree
Vincenza Lombardo, BS
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
26725064
Citation
Marasco G, Di Biase AR, Schiumerini R, Eusebi LH, Iughetti L, Ravaioli F, Scaioli E, Colecchia A, Festi D. Gut Microbiota and Celiac Disease. Dig Dis Sci. 2016 Jun;61(6):1461-72. doi: 10.1007/s10620-015-4020-2. Epub 2016 Jan 2.
Results Reference
result
PubMed Identifier
25403367
Citation
Wacklin P, Laurikka P, Lindfors K, Collin P, Salmi T, Lahdeaho ML, Saavalainen P, Maki M, Matto J, Kurppa K, Kaukinen K. Altered duodenal microbiota composition in celiac disease patients suffering from persistent symptoms on a long-term gluten-free diet. Am J Gastroenterol. 2014 Dec;109(12):1933-41. doi: 10.1038/ajg.2014.355. Epub 2014 Nov 18.
Results Reference
result
Links:
URL
https://doi.org/10.1016/j.humic.2018.12.001
Description
Results Reference
Learn more about this trial
Impact of a Low-FODMAP Gluten-free Diet on Gut Microbiota and Circulating miRNAs in Celiac Disease Patients
We'll reach out to this number within 24 hrs