Dietary Interventions and Butyrate Production in Behçet's Patients

Therapeutic Modulation of Butyrate Production in Behçet's Patients: a Dietary Intervention Trial

A dietary intervention trial will be performed on patients affected by Behçet's syndrome. Three different diets will be compared, analyzing their effects on the gut microbiota composition, on endogenous butyrate production and on the general symptoms in Behçet's patients.

Study Overview

• Status: Completed
• Conditions: Behcet Syndrome
• Intervention / Treatment: Dietary supplement: Vegetarian diet; Dietary supplement: Oral butyrate; Dietary supplement: Habitual diet

Detailed Description

A dietary intervention trial will be conducted with the use of three different diets in order to compare the effects of these diets on the gut microbiota composition, on endogenous butyrate production and on the general symptoms in Behçet's patients.

The study will be a randomized, open trial designed to test whether a vegetarian diet or an habitual diet supplemented with oral butyrate would benefit the butyrate production, the gut microbiota composition and the general symptoms of Behçet's patients, compared with the habitual diet.

The study will involve 30 subjects with Behçet syndrome. Patients will be randomly assigned to follow a 3-months isocaloric dietary profile with either:

• vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products
• habitual diet supplemented with 2.4g/day of oral butyrate
• habitual diet without supplementation At the baseline visit, subjects will be educated about the aims and methods of the clinical trial and will sign their informed consent form.

Anthropometric measurements, body composition, and blood and stool sampling will be obtained from each participant at the beginning and at the end of the intervention period. All subjects will be examined between 07.00 and 09.30 hours after a 12 h fasting period.

The following parameters will be analyzed both at the beginning and at the end of the intervention period:

• Complete blood count
• Lipid variables - total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides
• Glycemic profile - glucose, insulin, glycated hemoglobin (HbA1C), HOMA index
• Liver function tests - aspartate aminotransferase (AST), alanine transaminase (ALT), gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, prealbumin
• Kidney function tests - serum creatinine, urea, uric acid
• Mineral profile - sodium, potassium, magnesium, calcium
• Iron metabolism - iron, ferritin
• Vitamin profile - vitamin B12, folic acid, vitamin D
• Thyroid function - TSH
• Inflammatory markers - erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA)
• Serology for celiac disease - IgA, anti-transglutaminase antibodies (IgA), anti endomysium antibodies (IgA)
• Circulating levels of inflammatory cytokines
• Oxidative stress markers
• Gut microbiota composition
• Butyrate production

At the beginning and at the end of the intervention period, participants will be asked to complete a questionnaire, which will assess Behçet's symptoms frequency and severity. In addition, participants will be contacted by phone to complete a 24-hours recall in order to test the adherence to diets they have been assigned to.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Florence, Italy, 50134
    • AOU Careggi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients affected by Behçet's disease

Exclusion Criteria:

• Pregnancy or breastfeeding
• Presence of diabetes mellitus
• Presence of other immune-mediated diseases
• Presence or history of cancer in the last 5 years
• Presence of infectious diseases in the last 3 months
• No antibiotic therapy in the last 3 months
• No vegetarian or vegan diet
• No intake of pro- or pre-biotics in the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vegetarian diet; vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products	Dietary supplement: Vegetarian diet; Patients follow a vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products
Experimental: Habitual diet + oral butyrate; habitual diet supplemented with 2.4g/day of oral butyrate	Dietary supplement: Oral butyrate; Patients follow the habitual diet supplemented with 2.4g/day of oral butyrate
Active Comparator: Habitual diet; habitual diet without supplementation	Dietary supplement: Habitual diet; Patients follow the habitual diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of gut microbiota composition		0-3 months
Evaluation of butyrate production	For the extraction of SCFAs (and butyrate in particular) the method described in Schnorr et al. will be follow" [Schnorr SL, Candela M, Rampelli S, Centanni M, Consolandi C, Basaglia G,et al. Gut microbiome of the Hadza hunter-gatherers. Nat Commun 2014;5:3654]	0-3 months
Complete blood count	composite score	0-3 months
Lipid variables	composite score taking into account the levels of: total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides	0-3 months
Glycemic profile	composite score taking into account the levels of : glucose, insulin, glycated hemoglobin (HbA1C), HOMA index	0-3 months
Vitamin profile	composite score, taking into account the levels of: vitamin B12, folic acid, vitamin D	0-3 months
Liver function tests	composite score taking into account the levels of: aspartate aminotransferase (AST), alanine transaminase (ALT), gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, prealbumin	0-3 months
Kidney function tests	composite score taking into account the levels of : serum creatinine, urea, uric acid	0-3 months
Mineral profile	composite score taking into account the levels of: sodium, potassium, magnesium, calcium	0-3 months
Iron metabolism	composite score taking into account the levels of: iron, ferritin	0-3 months
Thyroid function	measurement of TSH levels	0-3 months
Inflammatory markers	composite score taking into account the levels of: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA)	0-3 months
Serology for celiac disease	composite score taking into account the levels of: IgA, anti-transglutaminase antibodies (IgA), anti endomysium antibodies (IgA)	0-3 months
Circulating levels of inflammatory cytokines	composite score	0-3 months
Oxidative stress markers	composite score	0-3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation Behçet's symptoms frequency and severity	Participants are asked to complete a questionnaire, which will assess Behçet's symptoms frequency and severity.	0-3 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Careggi

Publications and helpful links

General Publications

• Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behcet's disease: a review. World J Gastroenterol. 2015 Apr 7;21(13):3801-12. doi: 10.3748/wjg.v21.i13.3801.
• Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, Centanni M, Cianchi F, Gotti R, Emmi L, Brigidi P, Bizzaro N, De Bellis G, Prisco D, Candela M, D'Elios MM. Behcet's syndrome patients exhibit specific microbiome signature. Autoimmun Rev. 2015 Apr;14(4):269-76. doi: 10.1016/j.autrev.2014.11.009. Epub 2014 Nov 27.
• Wong JM. Gut microbiota and cardiometabolic outcomes: influence of dietary patterns and their associated components. Am J Clin Nutr. 2014 Jul;100 Suppl 1:369S-77S. doi: 10.3945/ajcn.113.071639. Epub 2014 Jun 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2017
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): July 5, 2019

Study Registration Dates

• First Submitted: August 31, 2017
• First Submitted That Met QC Criteria: September 6, 2017
• First Posted (Actual): September 7, 2017

Study Record Updates

• Last Update Posted (Actual): January 28, 2020
• Last Update Submitted That Met QC Criteria: January 27, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Stomatognathic Diseases; Mouth Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Vasculitis; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Behcet Syndrome
• Other Study ID Numbers: butyrate2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD will not be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No