Clinical trial NCT03586622: One Year Home Monitoring and Treatment of IBS Patients
Official title: Home Monitoring of IBS Patients: Long Term Effect of Low FODMAP Diet With Re-introduction and Probiotic Treatment VSL#3 on IBS Symptoms and Gut Microbiota
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: eHealth
Dietary Modification
Probiotics
Microbiome
Irritable Bowel Syndrome
Keywords: Home monitoring
Irritable Bowel Syndrome
Lead sponsor: Nordsjaellands Hospital
Sponsor class: OTHER
Collaborators: name: Colitis-Crohn Foreningen
name: Ferring Pharmaceuticals
name: Calpro AS
name: Muusmann forlag
name: Statens Serum Institut
name: Genetic Analysis AS
First posted: 2018-07-13
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Symptom Severity (5-Item visual analogue scale, IBS-SSS)
timeFrame: 4 weeks
Secondary outcomes:
measure: Symptom Severity (IBS-SSS) area under the curve (AUC)
timeFrame: 11 months
measure: Disease course, Copenhagen IBS Disease course Type
timeFrame: one year
measure: Compliance, FODMAP adherence Report scale (FARS)
timeFrame: 4 weeks
measure: Compliance, Medication Adherence Report Scale (MARS)
timeFrame: 4 weeks
measure: Stool consistency, Bristol Stool Chart
timeFrame: 4 weeks
measure: Low grade inflammation measured by Fecal calprotectin (FC) on any smart phone
timeFrame: One year
measure: Microbiome
timeFrame: 4 weeks and one year
measure: Symptom Severity (Time to and time in symptom remission, IBS-SSS)
timeFrame: 11 months
measure: Quality of life, IBS-QOL
timeFrame: Every 4 weeks
measure: Food registration
timeFrame: Every 4 weeks
measure: Patients feedback for improvement of the ehealth platform
timeFrame: One year
Other outcomes:
Locations:
city: Frederikssund
country: Denmark
facility: North Zealand university hospital, Gastro unit
state: Capital Region
Study officials:
affiliation: North Zealands University Hospital
name: Pia Munkholm, Professor
role: STUDY_DIRECTOR
References:
citation: 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.