Efficacy and Safety of IBS Digital Behavioral Treatment

Study Overview
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Brief Summary
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A Randomized, Double-Blind, Comparator-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Two Self-administered behavioral treatments for Adult Subjects with Symptomatic Irritable Bowel Syndrome (IBS).

Detailed Description
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EASITx is a pivotal study comparing two self-administered behavioral treatments for irritable bowel syndrome (IBS). The active treatment in EASITx is classified as Software as a Medical Device (SaaMD).

Official Title
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The Efficacy and Safety of IBS Digital Behavioral Treatment Study

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Device: Arm 1 - Active behavioral Treatment Arm (Regulora; Gut-Directed Hypnotherapy Software as a Medical Device - SaMD)
* Device: Arm 2 - Active Comparator behavioral treatment arm (MR-1; Muscle Relaxation, Software as a Medical Device - SaMD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 18-70 Confirmation of the IBS and IBS subtype diagnosis by a study site physician using Rome IV diagnostic criteria Possess an iPhone Operating System (iOS) Apple or Android smartphone or iOS tablet (iPad) released in 2015 or later Agreement to input information about their abdominal pain and bowel movements on a daily basis into Curebase software Agreement to have their anonymized data stored in the cloud for up to 2 years after the conclusion of the study, and to have the data used for research purposes. Agreement to maintain stable dosage of IBS medications during the course of treatment and not to add new IBS medication or stop current IBS medications unless directed to do so by the participants treating physician. Changes in treatment will be captured using a concomitant medication assessment. Average Worst Daily Pain Severity of >3 on a 11-point numeric rating scale (NRS) over the full 28-day pre-treatment symptom tracking period Consistent submission of Pain Severity scores via the Curebase app (data submitted on 80% or more of days in the symptom tracking window) Exclusion Criteria: Evidence of current structural intestinal abnormalities that better explain the participant's IBS symptoms (e.g., celiac disease, inflammatory bowel disease - Crohn's Disease and ulcerative colitis, prior abdominal surgeries such as weight loss surgery or bowel resection) Medication use, other illnesses or conditions that can explain their gastrointestinal symptoms e.g.,regular narcotic use or dependency, Over The Counter (OTC) stimulant laxative dependence (i.e, progressively larger doses of Senna or Bisacodyl containing compounds are needed to produce a bowel movement), history of radiation to the abdomen. Diagnosed and/or treated for a malignancy within the past 5 years (other than localized basal or squamous cell carcinomas of the skin) Current psychotherapy, hypnotherapy, or cognitive behavioral therapy (CBT) for IBS Inability to commit to completing all treatment sessions Have an unstable extraintestinal condition whose immediate or foreseeable treatment needs would realistically interfere with study demands, e.g., ability to participate in online treatment sessions or follow daily diary. Active psychiatric disorder (e.g., post-traumatic stress disorder, depression associated with high risk of suicidal behavior, psychotic or delusional disorders, dissociative disorders, or gross cognitive impairment) Subjects that report a current gastrointestinal infection or an infection within the 4 weeks prior to the evaluation that would otherwise obscure IBS symptoms. In cases of gastrointestinal infection baseline evaluation will be delayed a minimum of 4 weeks until after complete recovery. Current or recent use of a gut-targeted antibiotic such as Neomycin or Rifaximin during the 12 weeks prior to baseline assessment. In the case of treatment with rifaximin or neomycin, eligibility will be suspended for 12 weeks from the initial date of use. Any condition that an investigator feels may interfere with the conduct of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Randomized, Double-Blind, Comparator-Controlled, Parallel-Group Study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Arm 1 is an active behavioral treatment for IBS (Regulora; Gut-Directed Hypnotherapy Software as a Medical Device - SaMD). | Device: Arm 1 - Active behavioral Treatment Arm (Regulora; Gut-Directed Hypnotherapy Software as a Medical Device - SaMD)<br>* The active treatment consists of 7 unique video/audio recordings administered via a mobile application every other week for 12 weeks (SaMD). Since subjects in both the active and comparator treatment arms receive a behavioral treatment, the subjects are blinded to active treatment.<br>|
| Active Comparator: Arm 2<br>Arm 2 is a behavioral treatment (MR-1; Muscle Relaxation, Software as a Medical Device - SaMD) | Device: Arm 2 - Active Comparator behavioral treatment arm (MR-1; Muscle Relaxation, Software as a Medical Device - SaMD)<br>* The comparator treatment consists of an identical treatment platform, scheduling platform, and reminder platform as the Active Treatment Arm, but in place of Gut-Directed Hypnotherapy there is a comparator relaxation treatment administered on an identical schedule: 7 unique video/audio recordings administered via a mobile application every other week for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abdominal Pain Intensity Responder | The primary endpoint of this study is abdominal pain intensity. The Instrument is a 0-10 numeric rating scale (NRS, 0= no pain, 10= worst pain). The subject is asked daily to record their worst abdominal pain over the past 24-hours. An Abdominal Pain Intensity Responder is defined as a subject whose daily abdominal pain intensity averaged over the 4 weeks post-treatment (weeks 13 through 16) is at least 30% reduced compared to the daily abdominal pain intensity averaged over the 4 weeks pre-treatment (weeks -4 through -1). | Baseline score (average of daily score for weeks -4 through -1) was compared to 4-weeks post-treatment (average daily score for weeks 13 through 16) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abdominal Pain Intensity | The Instrument is a 0-10 numeric rating scale (NRS, 0= no pain, 10= worst pain). The subject is asked daily to record their worst abdominal pain over the past 24-hours. Mean change in reported abdominal pain intensity. | Baseline score (average of daily score for weeks -4 through -1) was compared to 4-weeks post-treatment (average daily score for weeks 13 through 16) | 
| Abdominal Pain Frequency | Mean change in reported abdominal pain frequency. The abdominal pain frequency is based on the frequency of abdominal pain measured using a 0-10 numeric rating scale (NRS, 0= no pain, 10= worst pain). The subject is asked daily to record their worst abdominal pain over the past 24-hours. Average abdominal pain frequency is defined as the average number of days per week during the 4-week post-treatment assessment period in which the subjects recorded a 1 or greater on the daily pain measurement. Only days during which an assessment is recorded will be included in the calculation of average abdominal pain frequency. Days where severity was >0 were considered a day with pain and were recorded as positive. Days with a score of 0 were days without pain. Mean represents the mean number of days per week in each time period with abdominal pain. A lower score is a better outcome. | Change from baseline (weeks -4 to -1 before treatment) to 4-week post treatment period (Weeks 13-16) | 
| Number of Participants With >=30% Improvement in Normal Bowel Movements (Scored as 3, 4, or 5 on the Bristol Stool Form Scale) | Number of Participants with a ≥ 30% improvement in the proportion of Bristol Stool Form Scale (BSFS) scores that fell within Group 2 (normal stools) compared with baseline (Weeks -4 through -1). The result represents the number of participants with ≥ 30% improvement in the percentage of normal stools The BSFS is a visual aid that allows patients to classify their bowel movements into seven groups ranging from a score of 1 (separate hard lumps) to 7 (watery, no solid pieces). The BSFS scores will be grouped as 1,2 (Group 1), 3,4,5 (Group 2) and 6,7 (Group 3). The mid-range bowel movements 3,4 and 5 (Group 2) define normal stools. | Baseline score (average of daily score for weeks -4 through -1) was compared to 4-weeks post-treatment (average daily score for weeks 13 through 16) | 
| Daily Stool Frequency | Mean change in reported daily stool frequency Analyses of change in daily stool frequency will only include participants with IBS-C and IBS-D. IBS-C and IBS-D subtypes will be analyzed independently. | Baseline score (average of daily score for weeks -4 through -1) was compared to 4-weeks post-treatment (average daily score for weeks 13 through 16) | 
| Health-related Quality of Life Using the IBS Quality of Life (QOL) Instrument | The IBS QOL is a 34 item IBS-specific, validated instrument. The 34 items are summed for a total score and then transformed to 0-100 scale with higher scores indicating better IBS specific quality of life. IBS QOL scores will be compared pre- and post-treatment and the mean difference compared by treatment. | Baseline (Week -4) to 4-weeks post-treatment (Week 16) | 
| Percent Overall Work Impairment Due to IBS Based on the Work Productivity and Activity Impairment (WPAI) Questionnaire | Productivity and absenteeism will be evaluated using the patient reported Work Productivity and Activity Impairment (WPAI) General Health score. The WPAI (Reilly 1993) is a 6-question survey of presenteeism (impairment at work / reduced on-the-job effectiveness) and absenteeism (work time missed). The WPAI-GH consists of six questions: 1 = currently employed; 2 = hours missed due to health problems; 3 = hours missed other reasons; 4 = hours actually worked; 5 = degree health affected productivity while working (using a 0 to 10 Visual Analogue Scale (VAS)); 6 = degree health affected productivity in regular unpaid activities (VAS). Outcomes are expressed as impairment percentages (0-100%) with higher numbers indicating greater impairment and less productivity (worse outcomes). | Baseline (Week -4) to 4-weeks post-treatment (Week 16) | 
| Percent Overall Activity Impairment Due to IBS Based on the Work Productivity and Activity Impairment (WPAI) Questionnaire | Productivity and absenteeism will be evaluated using the patient reported Work Productivity and Activity Impairment (WPAI) General Health score. The WPAI (Reilly 1993) is a 6-question survey of presenteeism (impairment at work / reduced on-the-job effectiveness) and absenteeism (work time missed). The WPAI-GH consists of six questions: 1 = currently employed; 2 = hours missed due to health problems; 3 = hours missed other reasons; 4 = hours actually worked; 5 = degree health affected productivity while working (using a 0 to 10 Visual Analogue Scale (VAS)); 6 = degree health affected productivity in regular unpaid activities (VAS). Overall activity impairment is based on responses to Question 6. Outcomes are expressed as impairment percentages (0-100%) with higher numbers indicating greater impairment and less productivity (worse outcomes). | 4-weeks post-treatment (Week 16) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBS - Irritable Bowel Syndrome, IBS, Irritable Bowel