Clinical trial NCT04770883: Psychological and Dietary Treatment in IBS
Official title: Phenotyping and Treatment of Primary Health Care IBS Patients. A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: Irritable Bowel Syndrome
Cognitive Behavioral Therapy
Diet Therapy
Low FODMAP Diet
Internet Based Cognitive Behavioral Therapy
Psychological Therapy
Psychological Parameters
Phenotyping of Irritable Bowel Syndrome Patients
Gastrointestinal Symptoms
Quality of Life
Irritable Bowel Syndrome Symptom Severity
Lead sponsor: Region Örebro County
Sponsor class: OTHER
First posted: 2021-02-25
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study design is an open labelled, randomized, controlled clinical trial, with a ratio 2:2:1.
Primary purpose: TREATMENT

Brief summary: Irritable Bowel Syndrome (IBS) is a common functional gastrointestinal (GI) condition which is strongly associated with dietary and psychosocial factors. Management of IBS remains challenging for primary health care.

The aim is to perform a comprehensive phenotyping of patients with IBS within the primary health care in Region Örebro County, Sweden. Following this phenotyping, the investigators will perform a prospective randomized controlled trial of two different treatments versus control as described below. Subsequently, the investigators want to evaluate the result of the treatments in order to see whether the presence of a certain phenotype can predict the efficacy of different treatments.

Our hypothesis is that the presence of certain baseline symptom characteristics in patients with IBS can predict how effective internet based cognitive behavioral therapy (iCBT) and low FODMAP (low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) treatment will be for each patient.

200 patients with IBS aged 18-65 years will be recruited from the primary health care in Region Örebro County.

The study plan is structured as follows:

1. Phenotyping of IBS patients. Investigation of the correlation between different psychological parameters, IBS symptom severity and Quality of Life.
2. The effect and outcome of 10-weeks internet-based cognitive behavioral therapy (iCBT) versus control in IBS patients.
3. The effect and outcome of 10-weeks low FODMAP diet versus control in IBS patients.
4. Comparison of iCBT and low FODMAP treatment in IBS patients and identification of baseline phenotypic characteristics predicting treatment outcome for both treatments.

Stool and blood samples will be taken before and after treatment for analysis of gut microbiota, proteomics and epigenetics and to correlate these with the clinical phenotype.

All participants will undergo phenotyping regarding GI symptoms and psychological variables using questionnaires. Participants will afterwards be randomised to either 10 weeks treatment with iCBT (80 participants), low FODMAP (80 participants) or control group (40 participants) (2:2:1 randomization). The control group will wait 10 weeks before being randomised to either iCBT (20 participants) or low FODMAP (20 participants).

Significance

This study will provide effective and individualized treatment for IBS patients. This may lead to the development of a guideline to improve the effectiveness of treatment and care for patients with IBS.

Detailed description: Part 1

Study design:

Cross-sectional observational study.

Study population:

200 IBS patients, M/F, age 18-65 years, will be recruited under a period of 4 years from the primary health care in Region Örebro County. Patients will also be recruited from the general public using websites, social media and advertisements.

Data collection:

After informed consent is signed, a doctor's assessment is made including medical history, physical examination and laboratory tests.

For assessment of the IBS symptoms but also comorbid conditions such as upper GI symptoms, somatization and psychiatric symptoms, 12 different validated questionnaires will be used to identify sub-populations (phenotypes).

All patients will be asked to fill in these questionnaires before starting, during and after treatment.

Stool and blood samples will be taken at baseline and after treatment and will be stored at a biobank for later analysis of microbiomics, proteomics and epigenetics.

Analysis:

Descriptive statistics to identify different IBS features, and Pearson's correlations to study between-person correlations in a correlation network to see which parameters correlate most with the IBS symptom scale (GSRS-IBS) and Quality of life (IBS-QoL). They will be used as the dependent variables in multiple linear regression analysis with the other parameters as independent variables.

Part 2 and 3

Study design:

Randomized controlled clinical trial.

Study population:

Patients will then be randomized to either iCBT (80 patients), Low FODMAP diet (80 patients) or control group (40 patients) (2:2:1 randomization). The control group will wait 10 weeks before being randomised to treatment with either iCBT (20 patients) or low FODMAP diet (20 patients).

Treatments:

iCBT and Low FODMAP diet (see below).

Analysis:

Treatment efficacy analysis using linear mixed models on the primary outcome measures with time as within-subject factor (random intercept random slope models) and group as between-subject factor, with the time-by-group interaction effect testing the hypothesis of a stronger response to treatment compared to waiting list control. Continuous variables will be used to maximize power. Within-person correlations between IBS features. Linear mixed models and latent class growth analysis to establish which baseline parameters of IBS predict the treatment effect on the GSRS-IBS and IBS-QoL. Cross-lagged panel models to investigate the temporal order of change in the different outcome variables, while controlling for stabilities over time and cross-sectional correlations.

Part 4

Comparison of psychological and dietary treatment in IBS patients. At this point the investigators will have 100 patients who were treated with ICBT and 100 patients who were treated with low-FODMAP diet. Treatment efficacy will be analyzed using linear mixed models on the primary outcome measures with time as within-subject factor (random intercept random slope models) and group as between-subject factor, with the time-by-group interaction effect testing the hypothesis of a stronger response to iCBT compared to low-FODMAP.

Power calculation:

It is estimated that 100 participants per group need to be included in the treatment studies and the analysis of predictors of treatment responses with regard to a dropout rate of 10% (part 2-4). For part 1, the analysis can be performed on the entire study population of 200 participants, which gives 90% power to be able to detect an effect size (Cohen's f² = 0.10) in multiple regression analysis with 9 independent variables (derived from questionnaire PHQ-9, GAD-7, PHQ-12, VSI, IBS-BRQ and NEO-FFI) predicting the severity of IBS symptoms (IBS-SSS and GSRS-IBS) and quality of life (IBS-QoL).

Eligibility criteria: Inclusion Criteria:

1. IBS symptom severity score of at least 175 (moderate to severe symptoms).
2. Age 18 to 65 years.

Exclusion Criteria:

1. Abnormal results on standard screening laboratory tests; this means that patients with abnormal thyroid-stimulating hormone (TSH), increased f-calprotectin or positive celiac disease serology will not be included.
2. Severe psychiatric, systemic inflammatory diseases, inflammatory bowel disease and other severe diseases such as cancer.
3. Current drug or alcohol abuse.
4. Inability to complete questionnaires in Swedish.
5. Current pharmacological treatment for their IBS symptoms, except for "over the counter" products such as loperamide or fiber.
6. Ongoing use of low FODMAP (Fermentable Mono-, di-, oligosaccharides, and polyols) diet. A current lactose free or gluten free diet will not be accepted. Earlier lactose or gluten free diet will be accepted after a wash-out period of at least 2 weeks.
7. Current psychological treatment.
8. Current psychological treatment.

Primary outcomes:
measure: Gastrointestinal Symptom Rating Scale-IBS (GSRS-IBS)
timeFrame: 10 weeks
measure: The IBS quality of life questionnaire (IBS-QoL)
timeFrame: 10 weeks
Secondary outcomes:
measure: Patient Health Questionnaire Anxiety module (GAD-7)
timeFrame: 10 weeks
measure: Patient Health Questionnaire Depression Module (PHQ-9)
timeFrame: 10 weeks
measure: Patient Health Questionnaire Somatic symptom severity ('somatization') module (PHQ-12)
timeFrame: 10 weeks
measure: Visceral Sensitivity Index (VSI) questionnaire
timeFrame: 10 weeks
measure: The Irritable Bowel Syndrome-Behavioural Responses Questionnaire (IBSBRQ)
timeFrame: 10 weeks
measure: Nepean Dyspepsia Index (NDI)
timeFrame: 10 weeks
measure: IBS severity scoring system (IBS-SSS)
timeFrame: 10 weeks
measure: Rome IV diagnostic questionnaire
timeFrame: 10 weeks
measure: The Neuroticism-Extraversion-Openness Five Factor Inventory-3 (NEO-FFI-3) questionnaire
timeFrame: 10 weeks
measure: Bristol Stool Form Scale
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Örebro
country: Sweden
facility: Skebäck primary health care center
Study officials:
References: