One Year Home Monitoring and Treatment of IBS Patients

NCT ID: NCT03586622

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-23
• Study Completion Date: 2020-12-20

Brief Summary

The purpose of this study Is to evaluate if a 4 weeks probiotic VSL#3 treatment and a strict LFD for 4 weeks are equally good in treating IBS symptoms in IBS patients with diarrhoea or mixed predominance and further evaluate the long term effect. Hopefully this one year individualized web-based IBS study will generate a fundament that could be used as a treatment in the primary care/sector to IBS patients.This one year study will be carried out based on an eHealth platform ibs.constant-care.com. Patients will self-measure on the web-program the first 4 weeks before randomization. The patients will fill out different questionnaires regarding symptom severity, adherence, stool consistency and frequency, quality of life, disease course type, food registration and weight. Nearly all of the questionnaires are illustrated to the patients in a traffic light manner (Green, Yellow and Red). They will also self-measure Fecal calprotectin on their smart phones and send in fecal samples for microbiome analysis. In this randomized cross over study - 104 IBS patients will be randomized to either a diet low in FODMAPs (fermentable, oligo-, di- and monosaccharides and polyols, LFD) or the probiotic product VSL#3® for 4 weeks. The probiotic group will receive 2 sachets a day (450 billions live bacteria in one sachet) for 4 weeks. After 4 weeks intervention (LFD or VSL#3) non responders, defined as a reduction of less than 50 points in IBS-SSS will after two weeks wash out period be crossed over. IBS patients randomized to LFD and responds to LFD will after a reintroduction counselling with dieticians at North Zealand university hospital after 4 weeks on a strict LFD start reintroducing high FODMAP foods until symptom flare (individual defined as either Yellow or Red, >175 in IBS-SSS). Hereafter they will go on a strict LFD again until symptom remission (IBS-SSS below 175, Green zone) - LFD responders will continue with this procedure for 10 months. IBS patients initially randomized to VSL#3 and are after 4 weeks of intervention characterized as responders will not be offered a LFD. Instead they will self- measure on the web with no intervention after the 4 weeks of VSL#3 treatment. When/if they reach a symptom flare ( again individually defined as either Yellow or Red, >175 point in IBS-SSS) they will be offered another 4 weeks VSL#3 treatment.

Detailed Description

IBS (irritable bowel syndrome) patients will be recruited from the out-patient clinic of North Zealand University Hospital, capitol region of Copenhagen, Denmark. Project investigator will give the patients all relevant information and forms needed to obtain a written informed consent. 104 IBS patients with diarrhoea or mixed type predominance will be included. Before enrollment, Patients will receive education on IBS and good toilet habit (squatty potty) etc. They will hereafter self-measure on a web-program the first 4 weeks in order to capture intra individual variation on the web and giving the patients time to learn how to use the 'tool': ibs.constant-care.com, in particular the primary end point IBS-SSS will be filled out several times during the first 4 weeks. The web algorithm for ibs.constant-care.com is specially designed for this trial. After 4 weeks on the 'web' IBS patients will be randomized to either Low FODMAP diet (LFD) or VSL#3 probiotic treatment (900 billions live bacteria/day) for 4 weeks. Patients randomized to the LFD group will be educated by a nutritionist in the diet and taught how to use a Danish Low FODMAP diet app in order to adhere to the LFD.

Non-responders (IBS-SSS<50) after 4 weeks intervention will have a 2 weeks wash out period and crossed over to the other intervention. LFD Responders (IBS-SSS ≥50) will be taught by a nutritionist at North Zealand University Hospital how to re-introduce foods high in FODMAPs and while re-introducing tightly monitor on the web-program. If LFD responders during the reintroduction period (10 months) will encounter a symptom flare individually defined as either Yellow or Red (that is > 175 on IBS-SSS) they will start on a strict LFD until symptom remission (<175 IBS-SSS) and so forth during the rest of the year. Responders to VSL#3 (IBS-SSS ≥50) will self-monitor on the 'web' and if the patients experience a symptom flare (again individually defined as either Yellow or Red - that is > 175 on IBS-SSS), they will be offered another 4 weeks VSL#3 treatment.

20 healthy controls will consecutively be included in the study and followed for a year on the web as well - they will not fill out as many questionnaires and is primarily included to have a background population and variation regarding the microbiome.

Patients will at inclusion receive their personal log in (Two Factor Authentication, 2FA) to ibs.constant-care.com and Calprosmart. Patients will register the below listed:

Severity scores system for IBS (IBS-SSS), web IBS-QoL (Quality of life), web Copenhagen IBS disease course, web Bristol Stool Chart and frequency, web FODMAP adherence rating scale (FARS), web Medication Adherence Rating Scale (MARS), web Evaluation questionnaire of the web program, web Evaluation questionnaire on food habits, web Fecal calprotectin (FC) on any smart Phone (CalproSmart app) Microbiome (patients will send in 2 fecal samples every time they send in samples - one for microbiome analysis (research biobank) and another one for a fecal biobank for future use. Weight, web IBS-SSS, QoL, BSC and frequency, FARS, MARS, FC, weight/BMI will be illustrated longitudinally to the patients in a traffic light manner (for ease of interpretation).

Conditions

eHealth; Dietary Modification; Probiotics; Microbiome; Irritable Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low FODMAP diet

Low FODMAP diet (LFD) Each IBS patient randomized to the Australian exclusion diet, Low FODMAP diet (LFD) group (n=52) will when allocated to LFD group have a one-hour counseling to the LFD by a nutritionist at the hospital. Within this one hour a diet anamnesis of the patient will be made in order to register the High FODMAP foods the patient is consuming (important that one find good low FODMAP substitutions). Based on the diet anamnesis optimization of the low FODMAP diet counseling can be made. They will receive hands-out with recipes, tips, meal plans, list of suitable low FODMAP foods and folder of foods they should avoid- most of information in the LFD folder patients will also find in the app 'Low FODMAP diet' which they will receive free of charge.

Group Type: EXPERIMENTAL

Low FODMAP diet (LFD)

Intervention Type: DIETARY_SUPPLEMENT

The Low FODMAP diet (LFD) is an acronym for Fermentable Oligo-, Di-, and Monosaccharides And Polyols - all of which are small osmotic active carbohydrates or sugar alcohols that are poorly absorbed in the small intestine and therefore easily fermented by the gut microbiota. The fact that they are fermented rapidly and osmotic active makes them potential and likely candidates for causing luminal distension due to accumulation of gas and water in the intestine.

VSL#3®

Each IBS patient randomized to the probiotic VSL#3 arm (n=52) will at randomization be given VSL#3 for 4 weeks (56 sachets) together with a leaflet on VSL#3 - holding information on the product from the manufacture regarding storage, nutritional information etc. If the patients have any questions regarding the treatment, they can ask the project investigator handing out the VSL#3 to them. They will be instructed in taking their VSL#3 (2 sachets a day) as described by the manufacturer

Group Type: EXPERIMENTAL

VSL#3®

Intervention Type: DIETARY_SUPPLEMENT

VSL#3® is a dietary supplement that helps maintain the balance of the intestinal flora. VSL#3® has been recognized and classified as GRAS (Generally Regarded as Safe) by a panel of experts in the USA for both adult and pediatric IBD and IBS patients. VSL#3® is a probiotic food containing 450 billion freeze-dried live lactic acid bacteria and bifidobacteria from 8 different strains per bag/sachet: Streptococcus thermophilus BT01, Bifidobacteria (B. breve BB02, B. longum\* BL03, B. infantis\* BI04), Lactobacillus acidophilus BA05, Lactobacillus plantarum BP06, Lactobacillus paracasei BP07, Lactobacillus delbrueckii subsp. bulgaricus\*\* BD08; \*Recently reclassified as B. animalis subsp. lactis \*\* Recently reclassified as L. helveticus. The recommended daily dose is 1-2 bags.

Interventions

Low FODMAP diet (LFD)

The Low FODMAP diet (LFD) is an acronym for Fermentable Oligo-, Di-, and Monosaccharides And Polyols - all of which are small osmotic active carbohydrates or sugar alcohols that are poorly absorbed in the small intestine and therefore easily fermented by the gut microbiota. The fact that they are fermented rapidly and osmotic active makes them potential and likely candidates for causing luminal distension due to accumulation of gas and water in the intestine.

Intervention Type: DIETARY_SUPPLEMENT

VSL#3®

VSL#3® is a dietary supplement that helps maintain the balance of the intestinal flora. VSL#3® has been recognized and classified as GRAS (Generally Regarded as Safe) by a panel of experts in the USA for both adult and pediatric IBD and IBS patients. VSL#3® is a probiotic food containing 450 billion freeze-dried live lactic acid bacteria and bifidobacteria from 8 different strains per bag/sachet: Streptococcus thermophilus BT01, Bifidobacteria (B. breve BB02, B. longum\* BL03, B. infantis\* BI04), Lactobacillus acidophilus BA05, Lactobacillus plantarum BP06, Lactobacillus paracasei BP07, Lactobacillus delbrueckii subsp. bulgaricus\*\* BD08; \*Recently reclassified as B. animalis subsp. lactis \*\* Recently reclassified as L. helveticus. The recommended daily dose is 1-2 bags.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Patients fulfilling the Rome III criteria for IBS.
• IBS patients classified as diarrhea or mixed type by the Bristol stool chart.
• Within normal BMI range (18.5-25)
• IBS patients who can read, speak and understand Danish
• Have a smart phone
• IBS patients that can manage going on Internet and wireless networks
• Above 18 years of age
• IBS-SSS>175

Exclusion Criteria

• IBS Patients with diagnosed co-morbidities like diabetes
• IBS patients that have undergone gastrointestinal surgery
• IBS patients on IBS medication
• IBS patients on alternative diets
• IBS patients diagnosed with celiac disease and lactose intolerance
• IBS patients with severe mental disturbance or alcohol/ other drug abuse.
• IBS diagnosed with predominate constipation or unspecified
• Has previously been on low FODMAP diet (Guided by professional nutritionist )
• Has been on any probiotic or antibiotic treatment within 3 months prior to inclusion
• IBS patients with a BMI below 18.5 and above 25
• IBS patients with a language barrier
• Below 18 years of age

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Colitis-Crohn Foreningen

OTHER

Sponsor Role: collaborator

Ferring Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Calpro AS

OTHER

Sponsor Role: collaborator

Muusmann forlag

UNKNOWN

Sponsor Role: collaborator

Statens Serum Institut

OTHER

Sponsor Role: collaborator

Genetic Analysis AS

UNKNOWN

Sponsor Role: collaborator

Nordsjaellands Hospital

OTHER

Sponsor Role: lead

Responsible Party

Pia Munkholm

MD and Professor in eHealth and epidemiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pia Munkholm, Professor

Role: STUDY_DIRECTOR

North Zealands University Hospital

Locations

North Zealand university hospital, Gastro unit

Frederikssund, Capital Region, Denmark

Countries

Denmark

References

Ankersen DV, Weimers P, Bennedsen M, Haaber AB, Fjordside EL, Beber ME, Lieven C, Saboori S, Vad N, Rannem T, Marker D, Paridaens K, Frahm S, Jensen L, Rosager Hansen M, Burisch J, Munkholm P. Long-Term Effects of a Web-Based Low-FODMAP Diet Versus Probiotic Treatment for Irritable Bowel Syndrome, Including Shotgun Analyses of Microbiota: Randomized, Double-Crossover Clinical Trial. J Med Internet Res. 2021 Dec 14;23(12):e30291. doi: 10.2196/30291.

Reference Type: DERIVED

PMID: 34904950 (View on PubMed)

Other Identifiers

H16023499

Identifier Type: -

Identifier Source: org_study_id