Efficacy and Safety of IBS Digital Behavioral Treatment (EASITx)

• ClinicalTrials.gov Identifier: NCT04133519
• Recruitment Status: Completed
• First Posted: October 21, 2019
• Results First Posted: May 4, 2022
• Last Update Posted: May 4, 2022
• Sponsor: metaMe Health
• Information provided by (Responsible Party): metaMe Health

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Irritable Bowel Syndrome	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)	Not Applicable

Detailed Description:

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 378 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A Randomized, Double-Blind, Comparator-Controlled, Parallel-Group Study
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Efficacy and Safety of IBS Digital Behavioral Treatment Study
• Actual Study Start Date: October 23, 2019
• Actual Primary Completion Date: October 28, 2020
• Actual Study Completion Date: October 26, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm 1; 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); 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.
Active Comparator: Arm 2; 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); 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.

Outcome Measures

Primary Outcome Measures :

1. Abdominal Pain Intensity Responder [ Time Frame: 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) ]

   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).

Secondary Outcome Measures :

1. Abdominal Pain Intensity [ Time Frame: 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) ]
   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.
2. Abdominal Pain Frequency [ Time Frame: Change from baseline (weeks -4 to -1 before treatment) to 4-week post treatment period (Weeks 13-16) ]

   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.

3. Number of Participants With >=30% Improvement in Normal Bowel Movements (Scored as 3, 4, or 5 on the Bristol Stool Form Scale) [ Time Frame: 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) ]
   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.
4. Daily Stool Frequency [ Time Frame: 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) ]
   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.
5. Health-related Quality of Life Using the IBS Quality of Life (QOL) Instrument [ Time Frame: Baseline (Week -4) to 4-weeks post-treatment (Week 16) ]
   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.
6. Percent Overall Work Impairment Due to IBS Based on the Work Productivity and Activity Impairment (WPAI) Questionnaire [ Time Frame: Baseline (Week -4) to 4-weeks post-treatment (Week 16) ]

   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).

7. Percent Overall Activity Impairment Due to IBS Based on the Work Productivity and Activity Impairment (WPAI) Questionnaire [ Time Frame: 4-weeks post-treatment (Week 16) ]

   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Curebase

San Francisco, California, United States, 94122

Sponsors and Collaborators

metaMe Health

Investigators

• Principal Investigator: Lucy Pun, DO; Elevated Health

  Study Documents (Full-Text)

Documents provided by metaMe Health:

Study Protocol and Statistical Analysis Plan  [PDF] June 12, 2020

More Information

Publications:

El-Serag HB. Impact of irritable bowel syndrome: prevalence and effect on health-related quality of life. Rev Gastroenterol Disord. 2003;3 Suppl 2:S3-11.

Ford AC, Bercik P, Morgan DG, Bolino C, Pintos-Sanchez MI, Moayyedi P. Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care. Gastroenterology. 2013 Dec;145(6):1262-70.e1. doi: 10.1053/j.gastro.2013.08.048. Epub 2013 Aug 28.

Leong SA, Barghout V, Birnbaum HG, Thibeault CE, Ben-Hamadi R, Frech F, Ofman JJ. The economic consequences of irritable bowel syndrome: a US employer perspective. Arch Intern Med. 2003 Apr 28;163(8):929-35. doi: 10.1001/archinte.163.8.929.

Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012 Jul;10(7):712-721.e4. doi: 10.1016/j.cgh.2012.02.029. Epub 2012 Mar 15.

Mayer EA, Tillisch K. The brain-gut axis in abdominal pain syndromes. Annu Rev Med. 2011;62:381-96. doi: 10.1146/annurev-med-012309-103958.

Lackner JM. The role of psychosocial factors in functional gastrointestinal disorders. Quigley, Hongo, Fukuda (eds): Functional and GI Motility Disorders. 2014(33):104-16.

Lacy BE, Patel H, Guerin A, Dea K, Scopel JL, Alaghband R, Wu EQ, Mody R. Variation in Care for Patients with Irritable Bowel Syndrome in the United States. PLoS One. 2016 Apr 26;11(4):e0154258. doi: 10.1371/journal.pone.0154258. eCollection 2016.

Blanchard EB, Greene B, Scharff L, Schwarz-McMorris SP. Relaxation training as a treatment for irritable bowel syndrome. Biofeedback Self Regul. 1993 Sep;18(3):125-32. doi: 10.1007/BF00999789.

Palsson OS. Hypnosis Treatment of Gastrointestinal Disorders: A Comprehensive Review of the Empirical Evidence. Am J Clin Hypn. 2015 Oct;58(2):134-58. doi: 10.1080/00029157.2015.1039114.

Lackner JM, Jaccard J, Keefer L, Brenner DM, Firth RS, Gudleski GD, Hamilton FA, Katz LA, Krasner SS, Ma CX, Radziwon CD, Sitrin MD. Improvement in Gastrointestinal Symptoms After Cognitive Behavior Therapy for Refractory Irritable Bowel Syndrome. Gastroenterology. 2018 Jul;155(1):47-57. doi: 10.1053/j.gastro.2018.03.063. Epub 2018 Apr 25. Erratum In: Gastroenterology. 2018 Oct;155(4):1281.

Flik CE, Laan W, Zuithoff NPA, van Rood YR, Smout AJPM, Weusten BLAM, Whorwell PJ, de Wit NJ. Efficacy of individual and group hypnotherapy in irritable bowel syndrome (IMAGINE): a multicentre randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 Jan;4(1):20-31. doi: 10.1016/S2468-1253(18)30310-8. Epub 2018 Nov 23.

Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002 Dec;123(6):2108-31. doi: 10.1053/gast.2002.37095. No abstract available.

Yeh VM, Schnur JB, Montgomery GH. Disseminating hypnosis to health care settings: Applying the RE-AIM framework. Psychol Conscious (Wash D C). 2014 Jun;1(2):213-228. doi: 10.1037/cns0000012.

Gonsalkorale WM, Miller V, Afzal A, Whorwell PJ. Long term benefits of hypnotherapy for irritable bowel syndrome. Gut. 2003 Nov;52(11):1623-9. doi: 10.1136/gut.52.11.1623.

Lowen MB, Mayer EA, Sjoberg M, Tillisch K, Naliboff B, Labus J, Lundberg P, Strom M, Engstrom M, Walter SA. Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome. Aliment Pharmacol Ther. 2013 Jun;37(12):1184-97. doi: 10.1111/apt.12319. Epub 2013 Apr 25.

Powell RA, Gee TL. The effects of hypnosis on dissociative identity disorder: a reexamination of the evidence. Can J Psychiatry. 1999 Nov;44(9):914-6. doi: 10.1177/070674379904400908.

Meyerson J, Konichezy A. Out-of-illness experience: hypnotically induced dissociation as a therapeutic resource in treating people with obstinate mental disorders. Am J Psychother. 2009;63(2):133-46. doi: 10.1176/appi.psychotherapy.2009.63.2.133. Erratum In: Am J Psychother. 2009;63(4):383. Myerson, Joseph [corrected to Meyerson, Joseph].

Hauser W, Hagl M, Schmierer A, Hansen E. The Efficacy, Safety and Applications of Medical Hypnosis. Dtsch Arztebl Int. 2016 Apr 29;113(17):289-96. doi: 10.3238/arztebl.2016.0289.

Patrick DL, Drossman DA, Frederick IO, DiCesare J, Puder KL. Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Dig Dis Sci. 1998 Feb;43(2):400-11. doi: 10.1023/a:1018831127942.

Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993 Nov;4(5):353-65. doi: 10.2165/00019053-199304050-00006.

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Williamson A. What is hypnosis and how might it work? Palliat Care. 2019 Jan 31;12:1178224219826581. doi: 10.1177/1178224219826581. eCollection 2019. No abstract available.

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Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997 Sep;32(9):920-4. doi: 10.3109/00365529709011203.

Palsson OS, Baggish JS, Turner MJ, Whitehead WE. IBS patients show frequent fluctuations between loose/watery and hard/lumpy stools: implications for treatment. Am J Gastroenterol. 2012 Feb;107(2):286-95. doi: 10.1038/ajg.2011.358. Epub 2011 Nov 8.

• Responsible Party: metaMe Health
• ClinicalTrials.gov Identifier: NCT04133519
• Other Study ID Numbers: MM001
• First Posted: October 21, 2019
• Results First Posted: May 4, 2022
• Last Update Posted: May 4, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by metaMe Health:

IBS - Irritable Bowel Syndrome; IBS; Irritable Bowel

Additional relevant MeSH terms:

Irritable Bowel Syndrome; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases