A Comparison of Three Different Treatment Options for Irritable Bowel Syndrome (CARIBS)

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

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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Other: Traditional dietary advice and low FODMAP content; Other: Optimized Medical treatment; Other: Low carbohydrate diet

Detailed Description

The study is a randomized controlled trial comparing three different treatments during four weeks:

1. 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

2. 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
3. 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

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Non-US/Non-Canadian
    • Gothenburg, Non-US/Non-Canadian, Sweden, 44331
      • Magnus Simrén

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diet A; Low carbohydrate diet	Other: Traditional dietary advice and low FODMAP content; Traditional dietary advice according to the Brittish Dietetic Association including reducing the intake of fermentable carbohydrates.
Active Comparator: Medical treatment; Optimized Medical treatment	Other: Optimized Medical treatment; 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.
Experimental: Diet B; Traditional dietary advice and low FODMAP content	Other: Low carbohydrate diet; Diet that contains a maximum of 10 energy percent of carbohydrates, 23 energy % proteins and 67 energy % fat.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Qualitative assessment	Patient's subjective experiences related to the dietary intervention described by qualitative methods.	Approx. at 3 months follow-up

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden

Publications and helpful links

General Publications

• Nybacka S, Törnblom H, Simren M, Störsrud S. The Role of Carbohydrates in Irritable Bowel Syndrome: Protocol for a Randomized Controlled Trial Comparing Three Different Treatment Options. JMIR Res Protoc. 2022 Jan 17;11(1):e31413. doi: 10.2196/31413.
• Algera JP, Storsrud S, Lindstrom A, Simren M, Tornblom H. Gluten and fructan intake and their associations with gastrointestinal symptoms in irritable bowel syndrome: A food diary study. Clin Nutr. 2021 Oct;40(10):5365-5372. doi: 10.1016/j.clnu.2021.09.002. Epub 2021 Sep 9.

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Actual): April 15, 2022
• Study Completion (Actual): April 29, 2022

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (Estimate): November 22, 2016

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: microbiota; carbohydrates; metabolomics; FODMAPS
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: Car-IBS 1511-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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