Irritable Bowel Syndrome Clinical Trial
Official title:
Long Term Effect of Web-based Low FODMAP Diet and Probiotic Treatment VSL#3 on IBS Symptoms and Gut Microbiota
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 (of course with possibility of
future improvements of the web algorithm) 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
ibsnoh.constant-care.dk, where patients after being educated to self-measure on the
web-program and having a 4 week measuring period on the 'web' before randomization. The
patients will fill out different questionnaires regarding symptom severity, adherence, stool
consistency, quality of life, disease course type, food registration and weight. Some 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 billons 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.
Status | Not yet recruiting |
Enrollment | 124 |
Est. completion date | December 2019 |
Est. primary completion date | December 2019 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Patients fulfilling the Rome III criteria for IBS. - IBS patients classified as diarrhea or mixed type by the Bristol stoochart. - Within normal BMI range (18.5-25) - IBS patients who can read, speak and understand Danish - Have a smartphone - 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 |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Nordsjaellands Hospital | Calpro AS, Colitis-Crohn Foreningen, Ferring Pharmaceuticals, Genetic Analysis AS, Muusmann forlag, Statens Serum Institut |
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Symptom Severity (5-Item visual analogue scale, IBS-SSS) | The IBS-SSS scale is constructed as a five item visual analog scale (VAS) which will be self-administrated by the patients on the web program. And results will be illustrated as a function of time in a traffic light manner to the patients (Mild, Green Zone <175, Moderate, Yellow Zone 175-300 and Severe, Red Zone > 300 on the IBS-SSS). IBS-SSS evaluates the intensity of IBS symptoms during the past 10 days with regards to: abdominal pain, distension, bowel habits, and interference with life in general. Each of the five items generates a maximum score of 100, which gives a maximum total score of 500 for all five items. A greater score indicates more severe symptoms. A cut off value for improvement/ responder of 50 point was recommended by Francis et al. 1997 and will also be used in this study to evaluate respond rates in the 2 arms. | 4 weeks | No |
Secondary | Symptom Severity (IBS-SSS) area under the curve (AUC) | The IBS-SSS scale is constructed as a five item visual analog scale (VAS) which will be self-administrated by the patients on the web program. Each of the five items generates a maximum score of 100, which gives a maximum total score of 500 for all five items. Results will be illustrated as a function of time in a traffic light manner to the patients (Mild, Green Zone <175, Moderate, Yellow Zone 175-300 and Severe, Red Zone > 300 on the IBS-SSS). The cumulative AUC for IBS-SSS, Red Zone, Yellow zone and Green zone after 11 months on the web program ibsnoh.conctant-care.dk will be used for long term evaluation of the effect of the interventions. | 11 months | No |
Secondary | Disease course, Copenhagen IBS Disease course Type | Based on epidemiology four figures have been developed to describe disease-course of IBS. These figures have been used in a retrospective study (Maagaard et al. 2016) to measure change in IBS disease course in IBS and IBD with co-existing IBS before and after a low FODMAP diet. The four figures depicting different types of disease courses is described as follows: Mild IBS with indolent course Mild IBS with aggressive course Chronic IBS with continuous course Chronic IBS with intermittent course The patients have to choose one figure representing their disease course type the best at inclusion and one year later. |
one year | No |
Secondary | Compliance, FODMAP adherence Report scale (FARS) | FODMAP Adherence Report Scale (FARS) was constructed to evaluate dietary adherence and was inspired by the validated Medication Adherence Report Scale by Byrne et al 2005. It consists of five questions regarding changing the diet, substituting the diet, forgetting to follow the diet and stop following the diet. Each of the five questions can be answered with the following options: 'always', 'often', 'sometimes', 'rare', and 'never' (scoring 1-5 points). A total score of 20 points or more (=80%) will be considered as adherence to the diet (Maagaard et al. 2016). | 4 weeks | No |
Secondary | Compliance, Medication Adherence Report Scale (MARS) | This questionnaire is measuring compliance to any medical/probiotic therapy by five questions with the following response options: always, often, sometimes, seldom, never (scoring 1-5 points). A total score of 20 points or more (=80%) will be considered as compliant | 4 weeks | No |
Secondary | Stool consistency, Bristol Stool Chart | To evaluate stool consistency, the Bristol Stool Scale will be used. The scale is composed of a simple visual chart accompanied by a text description that classifies stools in seven forms. The description differentiates among the following: type 1, separate hard lumps, like nuts; type 2, sausage-shaped but lumpy; type 3, like a sausage or snake but with cracks on its surface; type 4, like a sausage or snake, smooth and soft; type 5, soft blobs with clear-cut edges; type 6, fluffy pieces with ragged edges, a mushy stool; and type 7, watery, no solid pieces | 4 weeks and one year | No |
Secondary | Low grade inflammation measured by Fecal calprotectin (FC) on any smart phone | Calprotectin can be measured in stool and is a very sensitive marker for inflammation in the gastro intestinal tract. In IBS patients the use of this fecal biomarker is relative to patients with e.g. ulcerative colitis less clear but is used in this study for the purpose to detect low grade inflammation: below 200 mg/kg by using a FC home test, CalproSmart ((https://www.youtube.com/watch?v=wrTk7VumnSE).) | One year | No |
Secondary | Microbiome | The microbiome (same fecal samples) will be analyzed in 2 different ways. The method is based on culture independent 16S rRNA next generation sequencing. DNA from the patient fecal samples will be purified and 16S rRNA specific DNA will be amplified by polymerase chain reaction (PCR) technique of variable regions of the 16S rRNA gene and subsequently sequenced using Illumina 2x251 bp paired end sequencing on a MiSeq sequencing instrument. The dysbiosis index is based on polymerase chain reaction (PCR) technique of variable regions of 16S rRNA with selected 54 bacterial probes. Outcome from this analysis is a dysbiosis index (DI) ranging from 1 to 5 where 1 and 2 is definded as normobiobiotic and 3-5 is dysbiotic (5 more dysbiotc than 3 and 4). DI 'grade 1 and 2' is 'green' and defines normobiosis. Grade 3 I yellow and 4 and 5 is red (dysbiotic). |
4 weeks and one year | No |
Secondary | Symptom Severity (Time to and time in symptom remission, IBS-SSS) | The IBS-SSS scale is constructed as a five item visual analog scale (VAS) which will be self-administrated by the patients on the web program. Each of the five items generates a maximum score of 100, which gives a maximum total score of 500 for all five items. Results will be illustrated as a function of time in a traffic light manner to the patients (Mild, Green Zone <175, Moderate, Yellow Zone 175-300 and Severe, Red Zone > 300 on the IBS-SSS). Symptom remission is defined as green zone. We will count number of days that it takes for patients to reach green zone (symptom remission); less than 175 in IBS-SSS and time (days) in the green zone throughout 11 months. | 11 months | No |
Secondary | Quality of life, IBS-QOL | The IBS-QoL is a self-report QoL measure.The IBS-QoL consists of 34 items, each with a five-point response scale: Items 1, 2, 4, 8-10, 12, 13, 16, 25-29, 34: answer options: 1 = not at all 2 = slightly 3 = moderately 4 = quite a bit 5 = extremely. And regarding the items 3, 5-7, 11, 14, 15, 17-24, 30-33 the answer options are : 1 = not at all 2 = slightly, 3 = moderately, 4 = quite a bit, 5 = a great deal. The 34 items are based on the following eight variables; dysphoria, interference with activity, body image, health worry, food avoidance, social reactions, sexual relationships. The individual responses to the 34 items are summed in a total score (max score 170) and the recall period is the past month (Patrick, D. L, 1998). The individual responses to the 34 items are summed up and averaged to give a total score and then transformed to a 0-100 scale for ease of interpretation with lower scores indicating better IBS specific QoL. | One year | No |
Secondary | Patients feedback for improvement of the ehealth platform | In order to improve the web program for future use. A self-made questionnaire has been made consisting of 11 question regarding the use of the web program Constant Care. Patients will fill out the questionnaire at follow up (that is after one year on the web program). | one year | No |
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