Dried Chicory Root in IBD

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical pilot trial is to test the use of dried chicory root in patients with IBD. The main questions it aims to answer are: what the effect of a 4-week 10-20 g/day WholeFiberTM intervention on fecal calprotectin, IBD-complaints and QoL, serum inflammatory markers, gut microbiota and SCFA levels in patients with Crohn's disease and ulcerative colitis Participants will receive 1 sachet of 10g WholeFiberTM for the first 2 weeks (equals 8.5 g fiber), and 2 sachets of 10g WholeFiberTM per day for the last two weeks (equals 17 g fiber). Researchers will compare the above mentioned outcomes before and after the intervention.

Detailed Description
-----------------
Rationale: Inflammatory Bowel Diseases (IBD), of which Ulcerative Colitis (UC) and Crohn's Disease (CD) are the main types, includes recurring episodes of inflammation in the gastro-intestinal tract and severely impacts quality of life (QoL), leads to more hospitalization and increases the mortality risk. An impaired gut microbiota and lower levels of short-chain fatty acids (SCFA) have been linked to the pathophysiology. A higher fiber intake is linked to positive changes in the gut microbiota and increase SCFA-production, however patients with IBD consume too little dietary fiber. WholeFiberTM, a dried vegetable rich in 4 types of prebiotic fiber, may be an easy solution to increase dietary fiber intake, impact the gut microbiota and SCFA, IBD-complaints and health parameters. Objective: To explore the effect of a 4-week 10-20 g/day WholeFiberTM intervention on fecal calprotectin, IBD-complaints and QoL, serum inflammatory markers, gut microbiota and SCFA levels in patients with CD and UC. Study design: this is a 4-week pilot study with one arm to explore the effects of a WholeFiberTM intervention. Measurements will take place before and after the intervention, questionnaires will also be conducted halfway. Study population: in total 12 patients with mild to moderate IBD complaints will be included, of which 6 UC and 6 CD patients, to investigate if there is a difference between the two groups in efficacy of WholeFiberTM. Intervention: Subjects will receive 1 sachet of 10g WholeFiberTM for the first 2 weeks (equals 8.5 g fiber), and 2 sachets of 10g WholeFiberTM per day for the last two weeks (equals 17 g fiber). Main study parameters/endpoints: the primary parameter is change in fecal calprotectin after the 4-week intervention, which is a marker for inflammation in the gut. Secondary parameters are improvements in IBD-complaints, QoL, serum markers, and changes in the gut microbiota and increase in fecal SCFA-production. Moreover, it will be explored whether the response on the intervention will be different between UC and CD. Furthermore, an evaluation questionnaire will be conducted to assess feasibility and acceptance of the WholeFiberTM intervention in this population.

Official Title
-----------------
The Effect of Dried Chicory Root on Inflammation, Gut Microbiota and Complaints in Patients With Inflammatory Bowel Disease: a Pilot Study

Conditions
-----------------
Inflammatory Bowel Diseases, Dietary Exposure

Intervention / Treatment
-----------------
* Dietary Supplement: Dried Chicory Root


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged ≥18 years; Having a diagnosis of IBD (either UC or CD) and undergoing treatment at the policlinic at the University Medical Center Groningen; Mild or moderate IBD, defined as fecal calprotectin levels ≥100 μg and Harvey Bradshaw Index (HBI) <8 for CD patients or Simple Clinical Colitis Activity Index (SCCAI) <5 for UC patients; Using stable maintenance therapy for at least 12 weeks; Being able to read and speak Dutch; Willing to come to the University Medical Center Groningen for practical reasons (visiting the study site); Willing to continue their regular lifestyle patterns during the study. Exclusion Criteria: Having a medical history that may impact study outcomes, such as a diagnosis of diabetes mellitus type 2, heart disease, renal disease, cancer, celiac disease; Having an ileostomy or colostomy, as this greatly impacts bowel function and gut microbiota composition; Having a clinically significant stenosis; Use of antibiotics <4 weeks before study start; Use of prebiotics, probiotics and/or synbiotic (this should be stopped 4 weeks before start of the study) or other fiber supplements such as psyllium; Use of tube feeding or sib-feeding; Being pregnant or lactating; Participation in another clinical study at the same time; Unable or unwilling to comply to study rules

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Pilot study investigating the effect of additional dietary intake 10-20 gram of a dried vegetable fibre. The difference in outcomes before and after the intervention in fecal calprotectin, IBD complaints, QOL, serum inflammatory markers, gut microbiota and SCFA will be determined
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Before and after study in 6 patients with UC and 6 patients wiht CD<br>This is a 4-week before-after pilot study to explore the effectiveness of a WholeFiber Trademark (TM) intervention (a dried vegetable rich in prebiotic intrinsic fibers) on inflammation, fecal gut microbiota and metabolites, IBD-complaints and QoL and assesses its feasibility. In this before-after study, 12 patients with IBD will receive WholeFiberTM; of which 6 patients with CD and 6 patients with UC to assess if there is a difference in effect between these groups of patients. | Dietary Supplement: Dried Chicory Root<br>* Subjects will receive 1 sachet of 10g WholeFiberTM for the first 2 weeks (equals 8.5 g fiber), and 2 sachets of 10g WholeFiberTM per day for the last two weeks (equals 17 g fiber). WholeFiberTM is a fiber-rich dried vegetable made from the chicory root that contains four types of prebiotic fibers (inulin, pectin, cellulose, hemi-cellulose).<br>* Other names: WholeFiber Trademark (TM);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in fecal calprotectin | To explore the effect of a 4-week 10-20 g/day WholeFiberTM intervention on fecal calprotectin levels in patients with CD and UC. | difference between baseline and after 4-week intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IBD complaints by HBI for CD | To explore the effect of a 4-week WholeFiberTM intervention on IBD-complaints in patients with CD measured by the Harvey Bradshaw Index (HBI) | difference between baseline and after 4-week intervention | 
| Change in IBD complaints by SCCAI for UC | To explore the effect of a 4-week WholeFiberTM intervention on IBD-complaints in patients UC measured by the Simple Clinical Colitis Activity Index (SCCAI) | difference between baseline and after 4-week intervention | 
| Change in QOL measured by IBDQ | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on QoL measured by the IBDQ (Irvine 1999) | difference between baseline and after 4-week intervention | 
| Change in the Food-related Quality of Life (FrQOL) | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on Food-related QoL measured by a validated instrument by Hughes et al 2015 | difference between baseline and after 4-week intervention | 
| Change in stool consistency | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on stool consistency. Stool consistency will be measured using the validated Bristol Stool Chart. | difference between baseline and after 4-week intervention | 
| Change in stool frequency | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on stool frequency. Patients will be asked how often they defecated per day during the past week | difference between baseline and after 4-week intervention | 
| Change in fecal microbiota composition: Shannon-index | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on fecal microbiota composition. Next generation sequencing will be used ot determine bacterial richness (Shannon-index) | difference between baseline and after 4-week intervention | 
| Change in fecal microbiota composition by beta-diversity | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on fecal microbiota composition. Next generation sequencing will be used ot determine bacterial interindividual variations (beta-diversity) | difference between baseline and after 4-week intervention | 
| Change in fecal SCFA levels: lactate | To explore the effect of a 4-week WholeFiberTM intervention on fecal lactate in patients with CD and UC measured by a conductivity detector. | difference between baseline and after 4-week intervention | 
| Change in fecal SCFA levels: formate | To explore the effect of a 4-week WholeFiberTM intervention on fecal formate in patients with CD and UC measured by a conductivity detector. | difference between baseline and after 4-week intervention | 
| Change in fecal SCFA levels; butyrate | To explore the effect of a 4-week WholeFiberTM intervention on fecal butyrate in patients with CD and UC measured by a conductivity detector. | difference between baseline and after 4-week intervention | 
| Change in fecal SCFA levels: propionate | To explore the effect of a 4-week WholeFiberTM intervention on fecal propionate in patients with CD and UC measured by a conductivity detector. | difference between baseline and after 4-week intervention | 
| Change in fecal SCFA levels: acetate | To explore the effect of a 4-week WholeFiberTM intervention on fecal acetate in patients with CD and UC measured by a conductivity detector. | difference between baseline and after 4-week intervention | 
| Change in fecal acidity (pH) | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on fecal acidity (pH) by a PCE-228-R pH and redox meter in a stool sample. | difference between baseline and after 4-week intervention | 
| Change in fecal redox status | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on fecal redox status, measured by PCE-228-R instrument. | difference between baseline and after 4-week intervention | 
| Change in serum leukocytes | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on leukocytes count. | difference between baseline and after 4-week intervention | 
| Change in serum thrombocytes | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on thrombocytes. | difference between baseline and after 4-week intervention | 
| Change in serum iron status: serum iron | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC serum iron [micromol/L] | difference between baseline and after 4-week intervention | 
| Change in serum iron status: Total Iron Binding Capacity (TIBC) | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on Total Iron Binding Capacity (TIBC) [micromol/L] | difference between baseline and after 4-week intervention | 
| Change in serum iron status: ferritin | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on ferritin [microg/L] | difference between baseline and after 4-week intervention | 
| Change in serum iron status: transferrin | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on transferrin [g/L] | difference between baseline and after 4-week intervention | 
| Change in serum ALAT | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on Alanine Aminotransferase (ALAT). | difference between baseline and after 4-week intervention | 
| Change in serum ASAT | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on Aspartate Aminotransferase (ALAT). | difference between baseline and after 4-week intervention | 
| Change in serum GGT | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on Gamma-Glutamyl Transferase (GGT) | difference between baseline and after 4-week intervention | 
| Change in serum creatinine | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on iron status. | difference between baseline and after 4-week intervention | 
| Change in C-reactive protein (CRP) | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on C-reactive protein (CRP), which is an inflammation marker. | difference between baseline and after 4-week intervention | 
| Change in inflammatory marker IL-6 analysed by an ELISA kit | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on the inflammatory marker IL-6 on an ELISA kit | difference between baseline and after 4-week intervention | 
| Change in inflammatory marker IL-8 analysed by an ELISA kit | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on the inflammatory marker IL-8 on an ELISA kit | difference between baseline and after 4-week intervention | 
| Change in inflammatory marker IL-10 analysed by an ELISA kit | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on the inflammatory marker IL-10 on an ELISA kit | difference between baseline and after 4-week intervention | 
| Change in inflammatory markers IL-12 analysed by an ELISA kit | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on the inflammatory marker IL-12 on an ELISA kit | difference between baseline and after 4-week intervention | 
| Change in inflammatory markerIL-17a analysed by an ELISA kit | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on the inflammatory marker IL-17a on an ELISA kit | difference between baseline and after 4-week intervention | 
| Change in inflammatory marker IL-22 analysed by an ELISA kit | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on the inflammatory marker IL-22 on an ELISA kit | difference between baseline and after 4-week intervention | 
| Change in inflammatory marker IL-23 analysed by an ELISA kit | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on the inflammatory marker IL-23 on an ELISA kit | difference between baseline and after 4-week intervention | 
| Change in inflammatory marker TNF-alpha analysed by an ELISA kit | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on the inflammatory marker TNF-alpha on an ELISA kit | difference between baseline and after 4-week intervention | 
| Change in inflammatory marker Interferon(IFN)-gamma analysed by an ELISA kit | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on the inflammatory marker Interferon(IFN)-gamma on an ELISA kit | difference between baseline and after 4-week intervention | 
| Change in oxidative stress measured by free thiols | To explore the effect of a 4-week WholeFiberTM intervention in patients with CD and UC on oxidative stress measured by free thiols. | difference between baseline and after 4-week intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inflammatory bowel disease, dietary fiber, gut microbiome, inflammation