Behcet SyndromeNCT03962335
Gut Microbiota and Behcet's Syndrome: a Dietary Intervention Trial (MAMBA Study)
A study testing Vegetarian diet, Mediterranean diet with butyrate and Mediterranean diet in people with Behcet Syndrome, run by Azienda Ospedaliero-Universitaria Careggi at 1 site in Italy.
Trial summary
Behçet's syndrome (BS) is an idiopathic, chronic, multi-systemic inflammatory disorder characterized by ocular disease, skin lesions, vascular, neurological and gastrointestinal involvement. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Behcet Syndrome
- What is being tested?
- Vegetarian diet, Mediterranean diet with butyrate and Mediterranean diet
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteItaly
- Study dates
- 6 Jan 2019to 31 May 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Behcet syndrome
- Age 18-65 years
- Willing to give informed consent
- Willing to participate in a study where one of the proposed dietary profile is a vegetarian pattern
Who cannot join
- Pregnancy or lactation
- Concomitant presence of serious illness or unstable condition (autoimmune diseases; chronic viral infections; malignancies, recent myocardial infarction, chronic liver disease, inflammatory bowel diseases)
- Current or recent (past 6 months) participation in weight loss treatment program or use of weight loss medication
- Adoption of a vegetarian diet for the past 3 months
Trial locations and contacts
1 site in 1 country.
Italy1 site
Unit of Clinical Nutrition, University Hospital of Careggi
Florence, 50134
About this study
Official title: ModulAtion of Gut Microbiota Through Nutritional Interventions in Behcet's Syndrome pAtients: the MAMBA Study
Behçet's syndrome (BS) is an idiopathic, chronic, multi-systemic inflammatory disorder characterized by ocular disease, skin lesions, vascular, neurological and gastrointestinal involvement. A recent study showed a peculiar dysbiosis of gut microbiota (GM) in BS patients, with specific changes in the profiles of short-chain fatty acids, especially butyrate. Over the last few years, a growing interest on the role of GM in metabolic disturbances has been manifested. Diet is one of the major factors driving the GM composition and functionality. In this context, the influence of diets generally recognized healthy on GM has been explored, but consistent data on autoimmune and inflammatory diseases are not available. The aim of this intervention study is to investigate whether a lacto-ovo-vegetarian diet enriched in substrates with potential for butyrate production or a Mediterranean diet supplemented with oral butyrate could be beneficial for GM and metabolic risk profile in BS.
Read the detailed description
Background / State of Art:
Behçet's syndrome (BS) is a systemic inflammatory disorder characterized by a wide range of potential clinical manifestations with no gold-standard therapy. Although BS is usually not a life-threatening condition, mortality can be associated with vascular-thrombotic and neurological affections.
A recent study by our group, for the first time, provided evidence of a peculiar gut microbiota (GM) dysbiosis in BS patients, with reduced biodiversity, and decrease in short-chain fatty acid (SCFA)-producers and butyrate production. In light of this, controlled dietary interventions specifically designed to favor the increase of butyrate-producing members of the GM may support the recovery of a healthy GM ecosystem. Lacto-ovo-vegetarian diet is characterized by abstention from consuming meat and meat products, poultry, seafood and flesh from any other animal and by a large amount of plant- derived foods. This dietary pattern has been largely demonstrated to be beneficial for both patients with an established disease and for subjects with traditional risk factors for chronic diseases. Indeed, dietary patterns rich in plant-based food have been found to promote a more favorable GM profile, according to the high amount of dietary fiber and fermentable substrate, which are sources of metabolic fuel for GM fermentation that, in turn, result in end products - mainly SCFA - that are key microbial metabolites with a multifactorial role on the host health.
Hypothesis and Specific aims:
Although the pathogenesis of BS is currently unknown, it has been recently classified at the crossroad between autoimmune and autoinflammatory syndromes. GM has been found to deeply influence our metabolic and immunological health, and specific perturbed GM configurations have been indicating a fascinating link between intestinal microbes and health status. A recent study from our group showed that a peculiar dysbiosis of the GM ecosystem is present also in patients with BS, corresponding to specific changes in the profiles of SCFA production. In particular, the GM ecosystem in BS showed a low biodiversity, in line with several other chronic disorders. Moreover, a significant depletion of well- known butyrate producers, Roseburia and Subdoligranulum, and a corresponding decrease of butyrate production in BS patients was demonstrated. Butyrate - which is the preferred fuel for colonocytes - is able to induce T regulatory cell differentiation via several mechanisms, so the butyrate impairment in BS patients could favor a reduced T regulatory cell- mediated control, thus promoting a powerful immuno-pathological T cell responses.
In this context, over the last years, growing evidence suggested that high-fiber dietary patterns are able to promote a more favorable GM profile, and are key mediators of microbial diversity. In particular, it has recently been demonstrated that high adherence to a lacto-ovo-vegetarian diet - including high intake of non-refined cereals, fruit, vegetables and legumes - is associated with a beneficial GM profile, with enrichment in fiber-degrading bacteria and increase of fecal SCFA. In a similar way, other dietary patterns have been shown to modulate GM dysbiosis, by supporting the recovery of a balanced microbial community of health-promoting SCFA-producing members with the decrease of pro-inflammatory groups. Furthermore, current evidence indicates that the consumption of certain fibers - such as inulin and resistant starch - leads to specific GM rearrangements with the production of more butyrate than others in humans.
All these findings let hypothesize that the adherence to a controlled dietary profile such as lacto-ovo-vegetarian diet, possibly enriched in substrates with potential for butyrate production may select butyrate-producing bacteria - especially Roseburia spp. (Clostridium cluster XIVa) and Faecalibacterium prausnitzii (Clostridium cluster IV)- so reversing the pro- inflammatory dysbiosis observed in BS.
Preliminary Data:
A recent study by our group showed that a peculiar dysbiosis of the GM ecosystem is present in patients with BS, corresponding to specific changes in the profiles of SCFA production. By strengthening this dysbiotic GM structure, a significant decrease of fecal butyrate production was found in BS patients. More recently, a high percentage of Th1/Th17 cells at gut mucosal level in BS patients was observed, thus suggesting a reduced T regulatory activity, probably mediated by reduced levels of butyrate (unpublished data).
Specific Aim 1: To conduct a dietary intervention randomized controlled trial in order to investigate whether a lacto-ovo-vegetarian diet enriched in substrates with potential for butyrate production or a Mediterranean diet supplemented with 2 g/day of butyrate could be beneficial for GM and for the amelioration of the clinical manifestations and disease severity of patients with BS.
Specific Aim 2: To evaluate the effects of these interventions on: inflammatory parameters, circulating biomarkers of disease, endogenous butyrate production, and oxidative stress markers.
Specific Aim 3: To validate and extend our preliminary results on GM ecosystem dysbiosis in BS patients
- Conditions
- Behcet Syndrome
- Being tested
- Vegetarian diet, Mediterranean diet with butyrate, Mediterranean diet
- Keywords
- Gut microbiota, Mediterranean diet, Vegetarian diet, Short chain fatty acids
- Medical subject headings
- Behcet Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vegetarian dietBehavioural
Also called VD
7-days dietary profile with a Vegetarian diet (VD), containing inulin and resistant starch-rich foods and including no meat and fish, but containing eggs and dairy, for 3 months
Mediterranean diet with butyrateBehavioural
Also called MD+Bt
7-days dietary profile with Mediterranean diet with oral supplementation with butyrate (MD+Bt), 2 g/day, for 3 months
Mediterranean dietBehavioural
Also called MD
7-days dietary profile with Mediterranean diet (MD), including 2 portions per week of fish and 3 portions per week of fresh and processed meat (2 of which fresh or processed red meat), for 3 months
| Study group | Role | What they receive |
|---|---|---|
| VD group | Experimental | Group that starts with Vegetarian diet (VD) Receives: Behavioral: Vegetarian diet; Behavioral: Mediterranean diet with butyrate; Behavioral: Mediterranean diet |
| MD+Bt group | Experimental | Group that starts with Mediterranean diet with oral supplementation with butyrate (MD+Bt) Receives: Behavioral: Vegetarian diet; Behavioral: Mediterranean diet with butyrate; Behavioral: Mediterranean diet |
| MD group | Active comparator | Group that starts with Mediterranean diet (MD) Receives: Behavioral: Vegetarian diet; Behavioral: Mediterranean diet with butyrate; Behavioral: Mediterranean diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease severity of Behcet syndrome assessed by Behçet Disease Current Activity Form
The disease activity will be assessed by the use of the validated Behçet Disease Current Activity Form (BCDAF), at the baseline and after the dietary intervention. The BCDAF will assess the presence of oral and genital ulceration, skin, joint and gastrointestinal involvement, presence of fatigue and headache with a 5-point scale according to the duration of symptoms, with 0 meaning no symptoms and 4 meaning symptoms for 4 weeks. The presence of eyes, large vessels or central nervous system (CNS) involvement are document with "yes/no" answers. In addition, patients will be asked to rate on a 7-point scale how active they felt. Similarly, the clinicians will complete a 7-rating scale to assess their opinion of overall activity of the disease, with lower scores representing better outcomes.
Measured: 1 year
Behcet disease's improvement of symptoms assessed by the Global Assessment of Improvement Scale (GAI) modified form
The Global Assessment of Improvement Scale (GAI) modified form will assess Behcet disease's improvement of symptoms using a 7-point scale, with higher scores meaning an improvement of the symptoms. The severity of abdominal pain, severity of abdominal distention, satisfaction with bowel habits, severity of headache, severity of exhaustion, severity of nausea, attention disorder, muscle/joint pain, and quality of life will be investigated in response to the following question: "Compared to the way you felt before you entered the study, have your symptoms over the past 7 days been: 1) "Substantially Worse", 2) "Moderately Worse, 3) "Slightly Worse", 4) "No Change", 5) "Slightly Improved", 6) "Moderately Improved" or 7) "Substantially Improved".
Measured: 1 year
Behcet disease's severity of gastrointestinal symptoms assessed by the Symptom Severity Scale (SSS) modified form
The Symptom Severity Scale (SSS) modified form is a multidimensional rating scale assessing overall symptoms' severity on a Visual Analogue Scale (VAS). An overall score will be calculated from six items: pain severity, pain frequency, abdominal bloating, bowel habit dissatisfaction, abdominal heaviness, and life interference. The modified SSS ranges from 0 to 600, with higher scores meaning more severe symptoms.
Measured: 1 year
Secondary outcomes (6)
Gut microbiota assessed by Illumina MiSeq platform
Changes of gut microbiota profiles from baseline. The V3 and V4 hypervariable regions of the 16S rRNA gene will be sequenced on Illumina MiSeq platform, following the Illumina protocol for 16S Metagenomic Sequencing Library Preparation
Measured: 1 year
Fecal SCFA assessed by Gas Chromatography - Mass Spectrometry system
Fecal SCFA's change from baseline, especially butyrate, will be assessed by Gas Chromatography - Mass Spectrometry system
Measured: 1 year
Inflammatory profile assessed by cytofluorimetric approach
Inflammatory cytokines' change from baseline, will be assessed with the Bio-Plex cytokine assay, according to the manufacturer's instructions. In particular, Interleukin (IL)-1ra (pg/mL), IL-4 (pg/mL), IL-6 (pg/mL), IL-8 (pg/mL), IL-10 (pg/mL), IL-12 (pg/mL), IL-17 (pg/mL), monocyte chemoattractant protein (MCP)-1 (pg/mL), macrophage inflammatory protein (MIP)-1beta (pg/mL), vascular endothelial growth factor (VEGF) (pg/mL), tumor necrosis factor (TNF)-alpha (pg/mL), interferon (IFN)-gamma (pg/mL), interferon-gamma-induced protein (IP)-10 (pg/mL), will be measured.
Measured: 1 year
Lipid peroxidation assessed by flow cytometry
Lipid peroxidation markers' change from baseline will be estimated using the Thiobarbituric Acid Reactive Substances (TBARS, pg/mL) assay kit through the flow cytometry.
Measured: 1 year
Plasma total antioxidant capacity assessed by the oxygen radical absorbance capacity
Plasma total antioxidant capacity's (TAC, μmol/mL) change from baseline, will be measured using the oxygen radical absorbance capacity.
Measured: 1 year
Reactive oxygen species (ROS) assessed by flow cytometry
Leukocyte (lymphocyte, monocyte, and granulocyte) reactive oxygen species' (ROS, RFU) change from baseline will be assessed through flow cytometry
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2019
- Study start6 Jan 2019
- Primary completion31 May 2023
- Study completion31 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Behcet SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized crossover open dietary intervention study with 3 arms of intervention
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria Careggi
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Sofi, Azienda Ospedaliero-Universitaria Careggi
- Investigators
- Alessandro Casini, MD, Study director, Unit of Clinical Nutrition, University Hospital of Careggi, Florence, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03962335
- Sponsor's protocol ID
- MAMBA
- Status last verified
- Feb 2024
- First submitted
- 14 May 2019
- Last updated
- 2 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 25852265Consolandi 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.
PubMed 25435420Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology. 2009 Jan;136(1):65-80. doi: 10.1053/j.gastro.2008.10.080. Epub 2008 Nov 19.
PubMed 19026645Candela M, Rampelli S, Turroni S, Severgnini M, Consolandi C, De Bellis G, Masetti R, Ricci G, Pession A, Brigidi P. Unbalance of intestinal microbiota in atopic children. BMC Microbiol. 2012 Jun 6;12:95. doi: 10.1186/1471-2180-12-95.
PubMed 22672413Kosiewicz MM, Dryden GW, Chhabra A, Alard P. Relationship between gut microbiota and development of T cell associated disease. FEBS Lett. 2014 Nov 17;588(22):4195-206. doi: 10.1016/j.febslet.2014.03.019. Epub 2014 Mar 26.
PubMed 24681103Wong 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.
PubMed 24898225Sonnenburg ED, Sonnenburg JL. Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell Metab. 2014 Nov 4;20(5):779-786. doi: 10.1016/j.cmet.2014.07.003. Epub 2014 Aug 21.
PubMed 25156449Kabeerdoss J, Devi RS, Mary RR, Ramakrishna BS. Faecal microbiota composition in vegetarians: comparison with omnivores in a cohort of young women in southern India. Br J Nutr. 2012 Sep 28;108(6):953-7. doi: 10.1017/S0007114511006362. Epub 2011 Dec 20.
PubMed 22182464Haro C, Montes-Borrego M, Rangel-Zuniga OA, Alcala-Diaz JF, Gomez-Delgado F, Perez-Martinez P, Delgado-Lista J, Quintana-Navarro GM, Tinahones FJ, Landa BB, Lopez-Miranda J, Camargo A, Perez-Jimenez F. Two Healthy Diets Modulate Gut Microbial Community Improving Insulin Sensitivity in a Human Obese Population. J Clin Endocrinol Metab. 2016 Jan;101(1):233-42. doi: 10.1210/jc.2015-3351. Epub 2015 Oct 27.
PubMed 26505825Candela M, Biagi E, Soverini M, Consolandi C, Quercia S, Severgnini M, Peano C, Turroni S, Rampelli S, Pozzilli P, Pianesi M, Fallucca F, Brigidi P. Modulation of gut microbiota dysbioses in type 2 diabetic patients by macrobiotic Ma-Pi 2 diet. Br J Nutr. 2016 Jul;116(1):80-93. doi: 10.1017/S0007114516001045. Epub 2016 May 6.
PubMed 27151248Candela M, Maccaferri S, Turroni S, Carnevali P, Brigidi P. Functional intestinal microbiome, new frontiers in prebiotic design. Int J Food Microbiol. 2010 Jun 15;140(2-3):93-101. doi: 10.1016/j.ijfoodmicro.2010.04.017. Epub 2010 Apr 24.
PubMed 20471127International Team for the Revision of the International Criteria for Behcet's Disease (ITR-ICBD). The International Criteria for Behcet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol. 2014 Mar;28(3):338-47. doi: 10.1111/jdv.12107. Epub 2013 Feb 26.
PubMed 23441863Munoz-Gonzalez I, Jimenez-Giron A, Martin-Alvarez PJ, Bartolome B, Moreno-Arribas MV. Profiling of microbial-derived phenolic metabolites in human feces after moderate red wine intake. J Agric Food Chem. 2013 Oct 2;61(39):9470-9. doi: 10.1021/jf4025135. Epub 2013 Sep 19.
PubMed 24010549Pagliai G, Dinu M, Fiorillo C, Becatti M, Turroni S, Emmi G, Sofi F. Modulation of gut microbiota through nutritional interventions in Behcet's syndrome patients (the MAMBA study): study protocol for a randomized controlled trial. Trials. 2020 Jun 9;21(1):511. doi: 10.1186/s13063-020-04444-6.
PubMed 32517729
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ModulAtion of Gut Microbiota Through Nutritional Interventions in Behcet's Syndrome pAtients: the MAMBA Study
- ClinicalTrials.gov ID
- NCT03962335
- Acronym / sponsor ID
- MAMBA
- Conditions
- Behcet Syndrome
- Keywords
- Gut microbiota, Mediterranean diet, Vegetarian diet, Short chain fatty acids
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Azienda Ospedaliero-Universitaria CareggiUniversity, hospital or other
- Study start
- 6 Jan 2019 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 31 May 2023 (actual)
- First posted
- 24 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Behçet's syndrome (BS) is an idiopathic, chronic, multi-systemic inflammatory disorder characterized by ocular disease, skin lesions, vascular, neurological and gastrointestinal involvement. A recent study showed a peculiar dysbiosis of gut microbiota (GM) in BS patients, with specific changes in the profiles of short-chain fatty acids, especially butyrate. Over the last few years, a growing interest on the role of GM in metabolic disturbances has been manifested. Diet is one of the major factors driving the GM composition and functionality. In this context, the influence of diets generally recognized healthy on GM has been explored, but consistent data on autoimmune and inflammatory diseases are not available. The aim of this intervention study is to investigate whether a lacto-ovo-vegetarian diet enriched in substrates with potential for butyrate production or a Mediterranean diet supplemented with oral butyrate could be beneficial for GM and metabolic risk profile in BS.
Detailed description
Background / State of Art:
Behçet's syndrome (BS) is a systemic inflammatory disorder characterized by a wide range of potential clinical manifestations with no gold-standard therapy. Although BS is usually not a life-threatening condition, mortality can be associated with vascular-thrombotic and neurological affections.
A recent study by our group, for the first time, provided evidence of a peculiar gut microbiota (GM) dysbiosis in BS patients, with reduced biodiversity, and decrease in short-chain fatty acid (SCFA)-producers and butyrate production. In light of this, controlled dietary interventions specifically designed to favor the increase of butyrate-producing members of the GM may support the recovery of a healthy GM ecosystem. Lacto-ovo-vegetarian diet is characterized by abstention from consuming meat and meat products, poultry, seafood and flesh from any other animal and by a large amount of plant- derived foods. This dietary pattern has been largely demonstrated to be beneficial for both patients with an established disease and for subjects with traditional risk factors for chronic diseases. Indeed, dietary patterns rich in plant-based food have been found to promote a more favorable GM profile, according to the high amount of dietary fiber and fermentable substrate, which are sources of metabolic fuel for GM fermentation that, in turn, result in end products - mainly SCFA - that are key microbial metabolites with a multifactorial role on the host health.
Hypothesis and Specific aims:
Although the pathogenesis of BS is currently unknown, it has been recently classified at the crossroad between autoimmune and autoinflammatory syndromes. GM has been found to deeply influence our metabolic and immunological health, and specific perturbed GM configurations have been indicating a fascinating link between intestinal microbes and health status. A recent study from our group showed that a peculiar dysbiosis of the GM ecosystem is present also in patients with BS, corresponding to specific changes in the profiles of SCFA production. In particular, the GM ecosystem in BS showed a low biodiversity, in line with several other chronic disorders. Moreover, a significant depletion of well- known butyrate producers, Roseburia and Subdoligranulum, and a corresponding decrease of butyrate production in BS patients was demonstrated. Butyrate - which is the preferred fuel for colonocytes - is able to induce T regulatory cell differentiation via several mechanisms, so the butyrate impairment in BS patients could favor a reduced T regulatory cell- mediated control, thus promoting a powerful immuno-pathological T cell responses.
In this context, over the last years, growing evidence suggested that high-fiber dietary patterns are able to promote a more favorable GM profile, and are key mediators of microbial diversity. In particular, it has recently been demonstrated that high adherence to a lacto-ovo-vegetarian diet - including high intake of non-refined cereals, fruit, vegetables and legumes - is associated with a beneficial GM profile, with enrichment in fiber-degrading bacteria and increase of fecal SCFA. In a similar way, other dietary patterns have been shown to modulate GM dysbiosis, by supporting the recovery of a balanced microbial community of health-promoting SCFA-producing members with the decrease of pro-inflammatory groups. Furthermore, current evidence indicates that the consumption of certain fibers - such as inulin and resistant starch - leads to specific GM rearrangements with the production of more butyrate than others in humans.
All these findings let hypothesize that the adherence to a controlled dietary profile such as lacto-ovo-vegetarian diet, possibly enriched in substrates with potential for butyrate production may select butyrate-producing bacteria - especially Roseburia spp. (Clostridium cluster XIVa) and Faecalibacterium prausnitzii (Clostridium cluster IV)- so reversing the pro- inflammatory dysbiosis observed in BS.
Preliminary Data:
A recent study by our group showed that a peculiar dysbiosis of the GM ecosystem is present in patients with BS, corresponding to specific changes in the profiles of SCFA production. By strengthening this dysbiotic GM structure, a significant decrease of fecal butyrate production was found in BS patients. More recently, a high percentage of Th1/Th17 cells at gut mucosal level in BS patients was observed, thus suggesting a reduced T regulatory activity, probably mediated by reduced levels of butyrate (unpublished data).
Specific Aim 1: To conduct a dietary intervention randomized controlled trial in order to investigate whether a lacto-ovo-vegetarian diet enriched in substrates with potential for butyrate production or a Mediterranean diet supplemented with 2 g/day of butyrate could be beneficial for GM and for the amelioration of the clinical manifestations and disease severity of patients with BS.
Specific Aim 2: To evaluate the effects of these interventions on: inflammatory parameters, circulating biomarkers of disease, endogenous butyrate production, and oxidative stress markers.
Specific Aim 3: To validate and extend our preliminary results on GM ecosystem dysbiosis in BS patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Randomized crossover open dietary intervention study with 3 arms of intervention
| Arm | Type | Receives |
|---|---|---|
| VD group | Experimental | Behavioral: Vegetarian diet, Behavioral: Mediterranean diet with butyrate, Behavioral: Mediterranean dietGroup that starts with Vegetarian diet (VD) |
| MD+Bt group | Experimental | Behavioral: Vegetarian diet, Behavioral: Mediterranean diet with butyrate, Behavioral: Mediterranean dietGroup that starts with Mediterranean diet with oral supplementation with butyrate (MD+Bt) |
| MD group | Active comparator | Behavioral: Vegetarian diet, Behavioral: Mediterranean diet with butyrate, Behavioral: Mediterranean dietGroup that starts with Mediterranean diet (MD) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Behcet syndrome
- Age 18-65 years
- Willing to give informed consent
- Willing to participate in a study where one of the proposed dietary profile is a vegetarian pattern
Key exclusion criteria (4 listed)
- Pregnancy or lactation
- Concomitant presence of serious illness or unstable condition (autoimmune diseases; chronic viral infections; malignancies, recent myocardial infarction, chronic liver disease, inflammatory bowel diseases)
- Current or recent (past 6 months) participation in weight loss treatment program or use of weight loss medication
- Adoption of a vegetarian diet for the past 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vegetarian dietAlso: VD7-days dietary profile with a Vegetarian diet (VD), containing inulin and resistant starch-rich foods and including no meat and fish, but containing eggs and dairy, for 3 months | Behavioural | MD group, MD+Bt group, VD group |
| Mediterranean diet with butyrateAlso: MD+Bt7-days dietary profile with Mediterranean diet with oral supplementation with butyrate (MD+Bt), 2 g/day, for 3 months | Behavioural | MD group, MD+Bt group, VD group |
| Mediterranean dietAlso: MD7-days dietary profile with Mediterranean diet (MD), including 2 portions per week of fish and 3 portions per week of fresh and processed meat (2 of which fresh or processed red meat), for 3 months | Behavioural | MD group, MD+Bt group, VD group |
Primary outcome
Disease severity of Behcet syndrome assessed by Behçet Disease Current Activity Form
Time frame: 1 year
The disease activity will be assessed by the use of the validated Behçet Disease Current Activity Form (BCDAF), at the baseline and after the dietary intervention. The BCDAF will assess the presence of oral and genital ulceration, skin, joint and gastrointestinal involvement, presence of fatigue and headache with a 5-point scale according to the duration of symptoms, with 0 meaning no symptoms and 4 meaning symptoms for 4 weeks. The presence of eyes, large vessels or central nervous system (CNS) involvement are document with "yes/no" answers. In addition, patients will be asked to rate on a 7-point scale how active they felt. Similarly, the clinicians will complete a 7-rating scale to assess their opinion of overall activity of the disease, with lower scores representing better outcomes.
Behcet disease's improvement of symptoms assessed by the Global Assessment of Improvement Scale (GAI) modified form
Time frame: 1 year
The Global Assessment of Improvement Scale (GAI) modified form will assess Behcet disease's improvement of symptoms using a 7-point scale, with higher scores meaning an improvement of the symptoms. The severity of abdominal pain, severity of abdominal distention, satisfaction with bowel habits, severity of headache, severity of exhaustion, severity of nausea, attention disorder, muscle/joint pain, and quality of life will be investigated in response to the following question: "Compared to the way you felt before you entered the study, have your symptoms over the past 7 days been: 1) "Substantially Worse", 2) "Moderately Worse, 3) "Slightly Worse", 4) "No Change", 5) "Slightly Improved", 6) "Moderately Improved" or 7) "Substantially Improved".
Behcet disease's severity of gastrointestinal symptoms assessed by the Symptom Severity Scale (SSS) modified form
Time frame: 1 year
The Symptom Severity Scale (SSS) modified form is a multidimensional rating scale assessing overall symptoms' severity on a Visual Analogue Scale (VAS). An overall score will be calculated from six items: pain severity, pain frequency, abdominal bloating, bowel habit dissatisfaction, abdominal heaviness, and life interference. The modified SSS ranges from 0 to 600, with higher scores meaning more severe symptoms.
6 secondary outcomes
Gut microbiota assessed by Illumina MiSeq platform
Time frame: 1 year
Fecal SCFA assessed by Gas Chromatography - Mass Spectrometry system
Time frame: 1 year
Inflammatory profile assessed by cytofluorimetric approach
Time frame: 1 year
Lipid peroxidation assessed by flow cytometry
Time frame: 1 year
Plasma total antioxidant capacity assessed by the oxygen radical absorbance capacity
Time frame: 1 year
Reactive oxygen species (ROS) assessed by flow cytometry
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2024.
- Background: PubMed 25852265Skef 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.
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- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alessandro Casini, MD study director
Unit of Clinical Nutrition, University Hospital of Careggi, Florence, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vegetarian diet, Mediterranean diet with butyrate and Mediterranean diet in people with Behcet Syndrome, run by Azienda Ospedaliero-Universitaria Careggi at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease severity of Behcet syndrome assessed by Behçet Disease Current Activity Form (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03962335, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2024; AzTrials last refreshed its copy on 7 Nov 2026.