A Comparison of Three Different Treatment Options for Irritable Bowel Syndrome

Study Overview
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Brief Summary
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Irritable Bowel Syndrome is a common disease to which there is no curable treatment. Diet is considered to trigger symptoms associated with the clinical picture of IBS, and dietary treatment is thus believed to relieve the symptoms of IBS. As the disease is very heterogeneous in its manifestation, different treatment options might be indicated depending on the predominant symptom. To investigate the response to different dietary treatment options, a randomized controlled intervention trial will be carried out in adult patients (>18 y) with IBS according to Rome IV criteria. The aim of this study is to compare the response to two different dietary treatments or optimized medical treatment.

Detailed Description
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The study is a randomized controlled trial comparing three different treatments during four weeks: Combination of low FODMAP diet + traditional dietary advice (based on NICE recommendations) Eat at regular hours; 3 main meals and 3 snacks Eat in peace, chew the food properly Peel all fruits and vegetables Limit intake of spicy and fatty foods, coffe, alcohol, avoid fizzy drinks and chewing gum Choose soluble rather than insoluble fibres Avoid foods high in FODMAPs Diet low in carbohydrates 10 E% carbohydrates, 23 E% protein, 67 E% fat Larger amounts of fish, shellfish, meat, egg, dairy products (lactose free if wanted) nuts, seeds, oil, vegetables No sugary or starchy foods, e.g pasta, potatoes, bread, rice, most fruits No specific consideration about FODMAP content Optimized pharmacological tretament based on predominant symptom and previous experience with pharmacological treatmment. Pain/discomfort: Pain: Amitriptyline 25 mg. Increase to 50 mg if needed Episodic pain: Hyoscyamine 0,2mg 2x2; adjust dose if needed Pain with diarrhea: Amitriptyline 25 mg. Increase dose if needed Pain with constipation: Linaclotide 290 microgram 1x1 Constipation: Bulking agent (Sterculia gum (Inolaxol) 1x1. Increase to 1x3 if needed Osmotic laxative (Macrogol (Movicol) 1x1 Linaclotide 290 microgram 1x1 Diarrhea Loperamide 1x2 . Adjust dose if needed Cholestyramine 1x1. Increase ever 3-5 d as needed Ondansetron 4mg 1x1. Increase to 1x2-3 if needed Eluxadoline 100mg 1x2 Primary endpoint: IBS-SSS reduction >50 points

Official Title
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The Role of CARbohydrates in Irritable Bowel Syndrome (CARIBS): Protocol for a Randomized Controlled Trial Comparing Three Different Treatment Options

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Other: Traditional dietary advice and low FODMAP content
* Other: Low carbohydrate diet
* Other: Optimized Medical treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IBS according to ROME IV criteria, BMI 18-35, ability to communicate in Swedish, Gothenburg region resident Exclusion Criteria: Heart, liver, neurologic or psychiatric disease or illness Serious gastrointestinal diseases Celiac disease Diabetes Other conditions or surgery that affects the gastrointestinal function Hyperlipidemia Food allergy or intolerance other than lactose Adherence to a specific diet Being pregnant or breastfeeding Previously been treated with any of the intervention arms, including having tested all of the pharmacological treatment options of relevance for the symptom profile of the patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diet A<br>Low carbohydrate diet | Other: Traditional dietary advice and low FODMAP content<br>* Traditional dietary advice according to the Brittish Dietetic Association including reducing the intake of fermentable carbohydrates.<br>|
| Active Comparator: Medical treatment<br>Optimized Medical treatment | Other: Optimized Medical treatment<br>* Standard consultation by physician and if needed patients will receive medical treatment based on the most prominent symptom. Constipation: osmotic laxatives, linaclotide. Diarrhea: loperamid, bile acid binders. Pain: anti depressent, antispasmodics, linaclotide.<br>|
| Experimental: Diet B<br>Traditional dietary advice and low FODMAP content | Other: Low carbohydrate diet<br>* Diet that contains a maximum of 10 energy percent of carbohydrates, 23 energy % proteins and 67 energy % fat.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion (%) of patients who respond to treatment | A responder is defined as having an IBS-SSS reduction >50 points @ 4 weeks | Baseline to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in symptom severity | Absolute and percentage change in IBS-SSS | Baseline, 4 weeks, 3 and 6 months | 
| Determinants for GI symptoms by IBS-SSS | GI symptoms measured by IBS-SSS | Baseline, 4 weeks, 3 and 6 months | 
| Determinants for GI symptoms by GSRS-IBS | GI symptoms measured by GSRS-IBS | Baseline, 4 weeks, 3 and 6 months | 
| Predictors of response to treatment | Potential predictors include demographics, questionnaire data, microbiota, metabolites, immunology | Baseline to 4 weeks | 
| Adherence to allocated intervention | Including compliance to dietary intervention during 4 weeks, and long-term adherence during follow-up | Baseline, 4 weeks, 3 and 6 months | 
| Change in microbiota content | Fecal microbiota analysis using 16S technique | Baseline, 4 weeks, 6 months | 
| Change in extra-intestinal symptoms and quality of life | As assessed by IBS specific questionnaires | Baseline, 4 weeks, 3 and 6 months | 
| Change in metabolic profile | Metabolomics in serum and urine samples | Baseline, 4 weeks, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FODMAPS, carbohydrates, metabolomics, microbiota