This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR mHealth and uHealth, is properly cited. The complete bibliographic information, a link to the original publication on https://mhealth.jmir.org/, as well as this copyright and license information must be included.
Patients with irritable bowel syndrome (IBS) experience abdominal pain, altered bowel habits, and defecation-related anxiety, which can result in reduced productivity and impaired health-related quality of life (HRQL). Cognitive behavioral therapy (CBT) has been shown to reduce symptoms of IBS and to improve HRQL, but access to qualified therapists is limited. Smartphone-based digital therapeutic interventions have potential to increase access to guided CBT at scale, but require careful study to assess their benefits and risks.
The aim of this study was to test the efficacy of a novel app, Zemedy, as a mobile digital therapeutic that delivers a comprehensive CBT program to individuals with IBS.
This was a crossover randomized controlled trial. Participants were recruited online and randomly allocated to either immediate treatment (n=62) or waitlist control (n=59) groups. The Zemedy app consists of 8 modules focusing on psychoeducation, relaxation training, exercise, the cognitive model of stress management, applying CBT to IBS symptoms, reducing avoidance through exposure therapy, behavioral experiments, and information about diet. Users interact with a chatbot that presents the information and encourages specific plans, homework, and exercises. The treatment was fully automated, with no therapist involvement or communication. At baseline and after 8 weeks, participants were asked to complete the battery of primary (Irritable Bowel Syndrome Quality of Life [IBS-QOL], Gastrointestinal Symptom Rating Scale [GSRS]) and secondary (Fear of Food Questionnaire [FFQ], Visceral Sensitivity Index [VSI], Gastrointestinal Cognition Questionnaire [GI-COG], Depression Anxiety Stress Scale [DASS], and Patient Health Questionnaire-9 [PHQ-9]) outcome measures. Waitlist controls were then offered the opportunity to crossover to treatment. All participants were assessed once more at 3 months posttreatment.
Both intention-to-treat and completer analyses at posttreatment revealed significant improvement for the immediate treatment group compared to the waitlist control group on both primary and secondary outcome measures. Gains were generally maintained at 3 months posttreatment. Scores on the GSRS, IBS-QoL, GI-COG, VSI, and FFQ all improved significantly more in the treatment group (
Despite its relatively benign physical profile, IBS can be an extraordinarily debilitating condition. Zemedy is an effective modality to deliver CBT for individuals with IBS, and could increase accessibility of this evidence-based treatment.
ClinicalTrials.gov NCT04170686; https://www.clinicaltrials.gov/ct2/show/NCT04170686
Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder of multifactorial etiology that is characterized by abnormal centralized pain processing. IBS is defined by recurrent abdominal pain occurring at least one day per week in the last 3 months, associated with two or more of the following: related to defecation, associated with changes in the frequency or form of bowel movements (ie, characterized by constipation, diarrhea, or an alternating mix of the two). IBS is highly prevalent, affecting up to 10% of the US population. Many studies have demonstrated that IBS has high rates of psychiatric comorbidity (up to 90% in treatment-seeking patients) [
Illness-related anxiety is high among patients with IBS, and is a better predictor of impairment in quality of life than actual symptom severity [
Over the past two decades, cognitive behavioral therapy (CBT) has repeatedly proven to be an efficacious treatment for individuals suffering from IBS [
Although CBT is a promising treatment, access to IBS-specific CBT remains low for patients. There is a lack of clinicians competent in delivering GI-specific CBT [
Many groups have tested variants of CBT for IBS with limited or distant therapist involvement (eg, via email) [
In today’s digitized world, the mobile health (mHealth) industry is growing. The industry is currently valued at close to US $50 billion and is expected to multiply by nearly five times over the next decade [
CBT is among the forms of treatment increasingly being delivered via apps. In their review of eight CBT apps, Rathbone et al [
As self-help modalities are increasingly available online and through smartphone apps, it is important to test the efficacy of those apps through rigorous, controlled research. The purpose of this study was to test the efficacy of a novel digital app (Zemedy) that applies CBT to IBS.
This study was approved by the Institutional Review Board of the University of Pennsylvania. All participants provided electronic consent prior to participation in the study. The deidentified dataset analyzed in the study is available from the corresponding author upon request. This trial was registered at ClinicalTrials.gov as NCT04170686.
Zemedy 1.0 is a mobile phone app designed by Bold Health, a UK-based digital health company, in collaboration with the principal investigator (MH) based on her empirically supported self-help book [
Screenshots of Zemedy.
The app also includes a “flare module,” which users can access at any point to address immediate GI pain and anxiety. Shah et al [
Participants were provided with a link to download the app. They were provided the app at no cost. The entire intervention was delivered within the app with no human involvement (eg, therapist guidance or feedback). If participants experienced technical difficulties, they could reach out to technical support at Bold Health. They received a single email at 4 weeks from a research coordinator in the trial providing general encouragement to continue working through the app (if they were in the immediate treatment group) or to “hang in there” (if they were in the waitlist control group).
This was a randomized waitlist control crossover trial with assessments performed at baseline, postintervention (8 weeks), following crossover to intervention for the waitlist control group, and at follow-up (3 months postintervention). After completing the consent and all baseline measures, participants were randomly allocated by a research coordinator to either the immediate treatment or waitlist control group using the coin toss function of random.org. After 8 weeks, all participants were asked to complete the same battery of measures. At that point, participants in the waitlist group were crossed over and were given access to the app. After 8 weeks of access, they were asked to complete the battery of questionnaires again. All participants were then assessed one final time 3 months after completing the treatment phase. Unfortunately, the onset of the COVID-19 pandemic coincided with the follow-up portion of the trial, and it is unclear the extent to which the pandemic affected both attrition and long-term results.
The power analysis showed that 30 participants per randomized group would have 85% statistical power at a two-sided significance level of .05 to detect an effect size of 0.76. The effect size was chosen as previous studies of internet-delivered CBT for IBS reported similar effect sizes for HRQL and GI symptoms outcomes [
Inclusion criteria consisted of being 18 years of age or older, and reporting having been previously diagnosed by a physician with IBS or meeting the Rome IV criteria by self-report. We did not specify a time frame for the physician diagnosis; therefore, it is possible that some participants were originally diagnosed under Rome III criteria. Owning a smartphone and computer/internet literacy were de facto eligibility criteria.
Exclusion criteria consisted of reporting having received a diagnosis of another comorbid GI disorder such as celiac disease or an inflammatory bowel disease. Exclusion criteria also included severe depression and/or suicidal ideation, defined as a score of 20 or above on the Patient Health Questionnaire-9 (PHQ-9), and/or positive endorsement of active suicidal ideation or intent on a separate suicide question. Twenty-five individuals met this criterion. They were excluded from the trial, but were given immediate access to the app. The principal investigator, who is a licensed clinical psychologist, followed up with each of these individuals to complete a risk assessment and offer other resources such as referrals to local in-person providers.
A total of 146 potential participants were screened, 121 of whom met the inclusion criteria. Participants were recruited for the trial through IBS-specific social media sites with a combination of graphic advertisements, and posts and comments on threads informing site users about the study. Most participants came to the study through Facebook (n=30), Twitter (n=32), and the IBS subReddit (n=51). There were no face-to-face components to the trial in terms of recruitment, assessment, or intervention. Posts and advertisements included a link to a secure University of Pennsylvania Qualtrics study page. On following the link, potential participants would first see the detailed explanation of the research (consent form; see
All but five participants reported that they had been diagnosed with IBS by a physician at some point (which could have been under Rome III or Rome IV criteria). The five participants who did not report a physician diagnosis all met stringent Rome IV criteria by self-report. Of the 30 (24.8%) participants who reported a physician diagnosis but did not meet stringent Rome IV criteria, 7 reported pain 3 days a month and would have met Rome III criteria. Another 5 participants reported even less frequent pain. Four women reported pain solely during their menstrual period. Four people failed to meet the duration criteria (less than 6 months total since onset). The final 10 participants met only one, rather than two, of the three criteria beyond frequent abdominal pain.
With respect to IBS subtype, 48 (39.7%) participants reported diarrhea-predominant IBS, 28 (23.1%) reported mixed subtype, 11 (9.1%) reported constipation-predominant IBS, and 4 (3.3%) reported undifferentiated IBS. The remaining 30 (who did not meet all Rome IV criteria) were not divided into subtypes.
Participants who met the inclusion criteria were allocated to condition using the coin toss feature of random.org. A total of 62 participants were assigned to the immediate treatment condition and 59 were assigned to the waitlist control. The allocation sequence was concealed to participants until they were enrolled, had completed baseline data collection, and had been assigned to a group. The majority of baseline symptom severity measures were not significantly different between the immediate treatment and waitlist control groups. However, participants in the waitlist control group reported significantly more depression and more impaired HRQL than those in the immediate treatment group. Although the design should have yielded a low risk of bias from randomization, the slight differences in symptom severity at baseline suggest some concerns about randomization, according to the Cochrane risk of bias tool [
Because of the nature of the trial (immediate treatment versus waitlist control group), neither participants nor research coordinators were blinded to condition. However, there were no deviations from the intended intervention. Moreover, all outcome data were self-reported. Thus, blinding of evaluators was neither possible nor necessary.
Participants in the immediate treatment group were given the link to access the Zemedy app, and were encouraged to download it and begin working through the modules immediately. The waitlist control group was told they would be given access to the app in 8 weeks. Four weeks after baseline, participants in the treatment group were emailed to encourage them to continue using the app, and the waitlist control group was emailed to offer encouragement, remind them they were still enrolled in the study, and let them know that they would be receiving the follow-up questionnaires in 4 weeks.
Eight weeks after completing the baseline questionnaire, all participants were emailed a link to a second Qualtrics page that contained all of the same measures as completed at baseline. Those in the waitlist control condition were then given access to the app.
After having had access to the app for 8 weeks, participants in the waitlist control group were emailed a link to the third battery of questionnaires that was identical to the battery received by the treatment group after 8 weeks of app usage, which included the same measures as contained in the baseline battery.
Finally, all participants were emailed a final link to the last battery of questionnaires (again identical to the battery at baseline and posttreatment) 3 months after they completed the active treatment phase. Upon completion of each round of questionnaires, participants received US $20 in Amazon credit.
If at any point a participant had indicated a significant increase in depressive symptoms or the onset of suicidal ideation, the team would have alerted the principal investigator (a licensed clinical psychologist) who would have reached out to that individual to perform a risk assessment and offer referrals to local resources. No such adverse events occurred.
The IBS-Quality of Life (IBS-QOL) questionnaire is a 34-item self-report measure specific to IBS designed to assess the impact of IBS on quality of life [
The Gastrointestinal Symptom Rating Scale-IBS (GSRS-IBS) contains 13 self-report items rated on a 6-point Likert scale ranging from 1 (no discomfort at all) to 7 (very severe discomfort) [
We used a questionnaire to determine whether participants met the current Rome IV diagnostic criteria for IBS. Our questionnaire was based on the Rome IV IBS-Specific Questionnaire, which is a validated self-report scale that covers the diagnostic criteria for IBS. It has been found to have acceptable sensitivity and high specificity as well as good test-retest reliability [
The Fear of Food Questionnaire (FFQ) is an 18-item self-report questionnaire that measures fear, avoidance of food, as well as life interference and loss of pleasure from eating [
The Visceral Sensitivity Index (VSI) is a unidimensional 15-item scale that measures GI symptom–specific anxiety [
The Gastrointestinal Cognitions Questionnaire (GI-COG) consists of 16 self-report items that are rated on a 5-point Likert scale, ranging from 0 (hardly) to 4 (very much). Individual items are summed and total scores range from 0 to 64. The questionnaire consists of three subscales: the pain/life interference subscale (eg, “When I feel my GI symptoms acting up, I’m afraid the pain will be excruciating and intolerable”), the social anxiety subscale (eg, “If I have to get up and leave an event, meeting, or social gathering to go to the bathroom people will think there’s something wrong with me”), and the disgust sensitivity subscale (eg, “The thought of fecal incontinence is terrifying. If it happened, it would be awful”). The GI-COG has been shown to have excellent internal consistency (Cronbach α=.92) and test-retest reliability (r=0.87,
The Depression Anxiety Stress Scale (DASS) is a 42-item self-administered questionnaire that measures the magnitude of depression, anxiety, and stress independently. Internal consistency for each of the subscales of the questionnaire are high, with Cronbach α of .96 to .97 for DASS-Depression, .84 to .92 for DASS-Anxiety, and .90 to .95 for DASS-Stress [
The PHQ-9 is a depression scale that consists of 9 self-report items. The 9 items aim to quantify the 9 criteria upon which the diagnosis of depressive disorders is based in the Diagnostic and Statistical Manual of Mental Disorders-IV. The PHQ-9 can establish a depressive disorder diagnosis and depressive symptom severity [
Dosage was measured according to the number of modules completed. The mobile app sent usage data to the backend system each time a participant visited the app. Data include the time and date of each session on the app.
Univariate general linear models in SPSS V25 were used to examine between-group effects at posttreatment (8 weeks), controlling for baseline levels of the dependent variable. Paired-sample
Change in visceral anxiety, catastrophizing, and fear of food (calculated as the change from baseline to 8 weeks) were explored as possible mediators of GI symptoms and quality of life at 8 weeks using regression analysis with estimates of indirect effects calculated using a percentile bootstrap estimation approach with 5000 samples implemented with the PROCESS macro Version 3.5 [
The mean participant age was 32 years (SD 10.2, range 18-63). Of the total 121 participants, 76.0% (n=92) were white, 5.8% (n=7) were Hispanic, 5.0% (n=6) were black, 4.1% (n=5) were Asian, and the remaining 9.1% (n=11) identified as mixed race or other. With respect to gender, 75.2% (91/121) identified as female and 24.8% (30/121) identified as male. With respect to marital status, 43.0% (52/121) reported being single, 32.2% (39/121) reported being married, 19.0% (23/121) reported having a partner or cohabiting, and 5.8% (7/121) reported being divorced at baseline. With respect to employment, 22.3% (27/121) of the participants were students, 15.7% (19/121) reported being employed part time, 47.9% (58/121) reported being employed full time, and 14.0% (17/121) reported that they were not working when completing the baseline surveys. See
CONSORT diagram of participant flow through the study.
There were no significant differences between the immediate treatment and waitlist control groups on any of the demographic variables, or in baseline GI symptoms, visceral sensitivity, catastrophizing, or fear of food. However, as noted above, the waitlist control group was found to be slightly more distressed than the treatment group at baseline. The waitlist control group reported significantly more depression (PHQ-9, t119=2.99,
There were no univariate outliers found at baseline.
Completer analyses assessing the impact of treatment on outcome at 8 weeks revealed significant improvement for the immediate treatment group, relative to the waitlist control group, for both primary outcomes of GI symptom severity and HRQL (
For the immediate treatment group, all of the outcome variables changed significantly from pretreatment to posttreatment with the exception of the DASS Depression subscale, which showed only marginally significant improvement (
Mean (SD) outcome measures across the trial for the immediate treatment and waitlist control groups.
Outcome | Baseline | Eight weeks | Waitlist posttreatment (n=23) | Three months | |||||||
|
Immediate treatment (n=62) | Waitlist control (n=59) | Immediate treatment (n=36) | Waitlist control (n=44) |
|
Immediate treatment (n=24) | Waitlist control (n=21) | ||||
IBS-QOLa | 53.63 (18.67) | 60.48 (18.29) | 34.25 (19.78) | 58.19 (18.53) | 76.6 (20.07) | 38.08 (18.42) | 43.98 (21.1) | ||||
GSRSb | 36.76 (12.77) | 37.75 (12.02) | 27.56 (10.12) | 38.18 (10.79) | 34.26 (14.98) | 27.83 (9.37) | 30.95 (11.88) | ||||
GI-COGc | 36.92 (13.35) | 40.07 (12.04) | 22.44 (13.72) | 40.84 (11.23) | 33.3 (12.34) | 23.75 (12.06) | 31.71 (14.11) | ||||
VSId | 51.74 (12.29) | 53.54 (11.44) | 38.14 (16.21) | 53.57 (12.37) | 46.43 (12.78) | 41.08 (14.13) | 45.00 (12.63) | ||||
FFQe | 52.87 (19.14) | 55.46 (18.21) | 41.22 (22.23) | 53.75 (18.08) | 46.10 (19.87) | 42.83 (20.99) | 42.38 (19.87) | ||||
PHQf | 8.32 (5.29) | 11.03 (4.66) | 5.78 (4.20) | 10.32 (4.29) | 10.30 (5.80) | 6.92 (5.71) | 10.33 (5.97) | ||||
|
|
|
|
|
|
|
|
||||
|
Depression | 11.65 (9.88) | 15.59 (10.69) | 7.83 (7.88) | 15.45 (10.39) | 14.43 (10.89) | 9.08 (8.26) | 16.38 (12.89) | |||
|
Stress | 17.84 (9.56) | 18.71 (8.97) | 12.72 (8.65) | 18.82 (9.99) | 18.78 (10.03) | 15.08 (8.40) | 16.86 (9.69) | |||
|
Anxiety | 12.03 (7.35) | 12.19 (9.14) | 8.67 (6.38) | 12.05 (9.72) | 11.83 (9.72) | 9.08 (7.76) | 10.00 (6.99) |
aIBS-QOL: IBS Quality of Life.
bGSRS: Gastrointestinal Symptom Rating Scale.
cGI-COG: Gastrointestinal Cognitions Questionnaire.
dVSI: Visceral Sensitivity Index.
eFFQ: Fear of Food Questionnaire.
fPHQ: Patient Health Questionnaire.
gDASS: Depression Anxiety Stress Scale.
Significance of treatment allocation at 8 weeks using multiple imputation.
Measure | |||
IBS-QOLa | –2.8 | .005 | |
GSRSb | –2.8 | .005 | |
GI-COGc | –3.4 | .001 | |
VSId | –2.8 | .006 | |
FFQe | –2.4 | .02 | |
PHQf | –1.7 | .08 | |
|
|
|
|
|
Depression | –1.3 | .21 |
|
Stress | –1.2 | .25 |
|
Anxiety | –0.6 | .55 |
aIBS-QOL: IBS Quality of Life.
bGSRS: Gastrointestinal Symptom Rating Scale.
cGI-COG: Gastrointestinal Cognitions Questionnaire.
dVSI: Visceral Sensitivity Index.
eFFQ: Fear of Food Questionnaire.
fPHQ: Patient Health Questionnaire.
gDASS: Depression Anxiety Stress Scale.
Improvement from baseline to posttreatment for the immediate treatment group.
Measure | |||
IBS-QOLa | 4.368 | <.001 | |
GSRSb | 3.312 | .002 | |
GI-COGc | 5.603 | <.001 | |
VSId | 3.454 | .001 | |
FFQe | 3.523 | .001 | |
PHQf | 2.327 | .03 | |
|
|
|
|
|
Depression | 1.707 | .10 |
|
Stress | 2.273 | .03 |
|
Anxiety | 2.164 | .04 |
aIBS-QOL: IBS Quality of Life.
bGSRS: Gastrointestinal Symptom Rating Scale.
cGI-COG: Gastrointestinal Cognitions Questionnaire.
dVSI: Visceral Sensitivity Index.
eFFQ: Fear of Food Questionnaire.
fPHQ: Patient Health Questionnaire.
gDASS: Depression Anxiety Stress Scale.
In terms of
After completing the 8-week follow-up questionnaires, the waitlist group was crossed over to active treatment and was given access to the app for 8 weeks. Paired-samples
Improvement in the waitlist control group after crossover to active treatment.
Measure | |||
IBS-QOLa | –3.124 | .005 | |
GSRSb | –1.308 | .20 | |
GI-COGc | –2.748 | .01 | |
VSId | –2.618 | .02 | |
FFQe | –3.509 | .002 | |
PHQf | 0.103 | .92 | |
|
|
|
|
|
Depression | –1.537 | .14 |
|
Stress | –0.361 | .72 |
|
Anxiety | 0.360 | .72 |
aIBS-QOL: IBS Quality of Life.
bGSRS: Gastrointestinal Symptom Rating Scale.
cGI-COG: Gastrointestinal Cognitions Questionnaire.
dVSI: Visceral Sensitivity Index.
eFFQ: Fear of Food Questionnaire.
fPHQ: Patient Health Questionnaire.
gDASS: Depression Anxiety Stress Scale.
Three-month follow-up data were collected for all participants (both the immediate treatment group and the waitlist group who had been crossed over to treatment) between March and October of 2020. Unfortunately, this meant that all follow-up data were collected after the onset of the COVID-19 pandemic. Nevertheless, participants (all of whom had had access to the active treatment at this point) continued to show significant improvement over baseline on all outcome variables except depression (
Difference between baseline and 3-month follow-up data for all participants (N=121).
Measure | |||
IBS-QOLa | 5.136 | <.001 | |
GSRSb | 4.064 | <.001 | |
GI-COGc | 6.090 | <.001 | |
VSId | 4.261 | <.001 | |
FFQe | 4.000 | <.001 | |
PHQf | 1.489 | .14 | |
|
|
|
|
|
Depression | 0.499 | .62 |
|
Stress | 2.264 | .03 |
|
Anxiety | 3.012 | .004 |
aIBS-QOL: IBS Quality of Life.
bGSRS: Gastrointestinal Symptom Rating Scale.
cGI-COG: Gastrointestinal Cognitions Questionnaire.
dVSI: Visceral Sensitivity Index.
eFFQ: Fear of Food Questionnaire.
fPHQ: Patient Health Questionnaire.
gDASS: Depression Anxiety Stress Scale.
Finally, we assessed maintenance of treatment gains from posttreatment to 3-month follow-up. Without exception, gains were maintained, and there were no significant changes or relapse in symptoms, except for a slight rise in depression. Thus, even in the face of an incredibly stressful global pandemic, by and large, our participants showed remarkable resilience, and their HRQL, GI symptoms, GI-specific catastrophizing, anxiety, and fear of food remained much improved (
Maintenance of gains from posttreatment to 3 months.
Measure | |||
IBS-QOLa | 0.289 | .77 | |
GSRSb | 0.636 | .53 | |
GI-COGc | 0.841 | .41 | |
VSId | 0.056 | .96 | |
FFQe | 0.240 | .81 | |
PHQf | –0.530 | .60 | |
|
|
|
|
|
Depression | –1.614 | .11 |
|
Stress | 0.335 | .74 |
|
Anxiety | 0.935 | .36 |
aIBS-QOL: Irritable Bowel Syndrome-Quality of Life.
bGSRS: Gastrointestinal Symptom Rating Scale.
cGI-COG: Gastrointestinal Cognitions Questionnaire.
dVSI: Visceral Sensitivity Index.
eFFQ: Fear of Food Questionnaire.
fPHQ: Patient Health Questionnaire.
gDASS: Depression Anxiety Stress Scale.
Intention-to-treat sensitivity analysis of within-group changes using multiple imputation.
Measure | 0-8 weeks, immediate treatment group (n=62) | 8 weeks to posttreatment, waitlist group (n=59) | Posttreatment to 3-month follow-up, all participants (N=121) | ||||||
|
|||||||||
IBS-QOLa | 4.7 | <.001 | 3.5 | .001 | –0.47 | .65 | |||
GSRSb | 3.3 | .001 | 2.0 | .06 | 0.19 | .85 | |||
GI-COGc | 5.2 | <.001 | 2.9 | .008 | 0.10 | .93 | |||
VSId | 3.7 | <.001 | 2.4 | .02 | –0.26 | .80 | |||
FFQe | 3.2 | .002 | 2.0 | .047 | –0.15 | .88 | |||
PHQf | 2.1 | .04 | 2.0 | .053 | –0.32 | .75 | |||
|
|
|
|
|
|
|
|||
|
Depression | 1.2 | .23 | 1.8 | .08 | –0.87 | .39 | ||
|
Stress | 2.4 | .02 | 1.5 | .15 | 0.47 | .64 | ||
|
Anxiety | 2.3 | .02 | 1.9 | .07 | –0.14 | .89 |
aIBS-QOL: Irritable Bowel Syndrome-Quality of Life.
bGSRS: Gastrointestinal Symptom Rating Scale.
cGI-COG: Gastrointestinal Cognitions Questionnaire.
dVSI: Visceral Sensitivity Index.
eFFQ: Fear of Food Questionnaire.
fPHQ: Patient Health Questionnaire.
gDASS: Depression Anxiety Stress Scale.
There was significant attrition from the study in both the immediate treatment and waitlist control groups (see
Another aim of the study was to test whether changes in catastrophic thinking, visceral sensitivity, and fear of food would at least partially mediate reductions in GI symptom severity and improvement in quality of life.
The simple mediator models for GI symptom severity showed that changes in visceral anxiety, catastrophizing, and fear of food were all significant mediators of the relationship between treatment and GI symptom severity. Participants assigned to immediate treatment had a greater decrease in visceral anxiety, catastrophizing, and fear of food, and participants who had a greater decrease in visceral anxiety, catastrophizing, and fear of food had lower GI symptom severity at 8 weeks while controlling for baseline GI symptom severity (
Participants assigned to immediate treatment had a greater decrease in visceral anxiety, catastrophizing, and fear of food, and participants who had a greater decrease in visceral anxiety, catastrophizing, and fear of food had lower scores on IBS-QOL at 8 weeks while controlling for baseline IBS-QOL (
Direct and indirect mediation results.
Measure | GIa symptom severity | IBSb quality of life | ||||||||
|
Effect (95% BCIc) | Effect (95% BCI) | ||||||||
|
|
|
|
|
||||||
|
Indirect | –4.3 (–7.0 to –1.8) | .002 | –12.2 (–18.62 to –6.4) | <.001 | |||||
|
Direct | –5.1 (–8.8 to –1.4) | .007 | –4.6 (–9.8 to –.56) | .08 | |||||
|
|
|
|
|
||||||
|
Indirect | –3.7 (–7.1 to –1.2) | .007 | –15.4 (–21.6 to –9.6) | <.001 | |||||
|
Direct | –5.6 (–10.2 to –1.1) | .02 | –1.4 (–7.9 to 5.1) | .67 | |||||
|
|
|
|
|
||||||
|
Indirect | –4.0 (–7.2 to –1.5) | .003 | –9.8 (–16.3 to –3.8) | <.001 | |||||
|
Direct | –5.4 (–9.1 to –1.6) | .005 | –7.0 (–12.7 to –1.4) | .02 | |||||
|
|
|
|
|
||||||
|
Direct | –9.4 (–13.5 to –5.3) | <.001 | –.5 (–5.2 to 4.2) | .83 | |||||
|
Visceral anxiety | –3.4 (–6.2 to –1.0) | N/Ad | –7.0 (–11.3 to –3.4) | N/A | |||||
|
COGe | 1.8 (–1.0 to 4.4) | N/A | –5.1 (–9.0 to –1.8) | N/A | |||||
|
Fear of food | –2.7 (–5.5 to –0.8) | N/A | –4.3 (–8.3 to –1.2) | N/A |
aGI: gastrointestinal.
bIBS: irritable bowel syndrome.
cBCI: bias-corrected confidence interval.
dN/A: not applicable.
eCOG: cognition.
Univariate analysis of the data revealed that Rome IV criteria moderated the effectiveness of the treatment. That is, there was a significant interaction between condition and Rome IV status such that the app was more helpful to the participants who reported meeting stringent Rome IV criteria for IBS at baseline than for those who did not, for both GI symptoms (
We also examined whether IBS subtype moderated the efficacy of the app; it did not.
Because the app itself tracks objective progress through the modules, we were able to examine the effect of “dose” (measured as components of the app accessed) on outcome. The majority of participants in the immediate treatment group who completed follow-up surveys finished just shy over 3 modules (mean 3.2, SD 2, median 2.9). Only one participant completed all possible modules. Dosage was marginally correlated with improvement in HRQL (
The purpose of this study was two-fold. First, we tested the efficacy of a cognitive behavioral intervention for IBS delivered via a digital self-help app, with no therapist feedback or involvement. Completer analyses yielded statistically and clinically significant improvement, with treatment having a positive impact on both GI symptom severity and quality of life. Intention-to-treat sensitivity analysis using multiple imputation replicated those findings. After treatment, individuals reported significantly lower levels of IBS symptoms and less impairment to their quality of life. Effect sizes for the primary outcomes and most of the secondary outcomes were all in the very large range. This 8-week intervention appears to have substantially reduced the burden of illness compared to that of waitlist controls.
Second, we tested whether reductions in IBS-specific catastrophic thinking, visceral sensitivity, and fear of food might mediate the efficacy of treatment. Reductions in these three variables did appear to mediate the impact of treatment on HRQL, but not on GI symptoms themselves. The app worked by reducing catastrophic thinking, visceral sensitivity to GI symptoms, and fear of food, which in turn improved individuals’ quality of life. This is consistent with prior findings about the impact of CBT on IBS. Additionally, changes in catastrophizing and visceral anxiety were observed in participants who had only completed the preliminary modules of the app. This is consistent with the idea that psychoeducation and relaxation can promote cognitive reframing and can reduce anxiety about visceral sensations.
Overall, we are strongly encouraged by the results of this study, which appear to suggest that effective CBT for IBS can be successfully delivered via an app. The Zemedy app seems to be an effective means to improve the lives of individuals with IBS. Zemedy, which is already in the App Store and Google Play Store for download, could dramatically increase the accessibility of effective treatment for this debilitating disorder.
This study had a number of limitations. The first was the lack of a placebo control condition. Patients with IBS typically show high placebo response rates [
The second major limitation was the lack of rigorous diagnostic interviewing or explicit physician confirmation of the IBS diagnosis. Our inclusion criteria were self-reported as a prior physician diagnosis of IBS and/or meeting stringent Rome IV criteria. Five participants had no physician diagnosis but met Rome IV criteria. Thirty participants reported having been diagnosed by a physician but did not meet stringent Rome IV criteria. Of those, 7 would have met Rome III [
The choice to include participants who did not meet Rome IV criteria was made because the aim of the study was to determine the efficacy of the app for individuals
The third limitation was the rate of attrition, with 36% not completing follow-up measures. Of those who completed 8-week follow-up measures, most had not made it through a substantial portion of the app’s content. Nevertheless, the attrition rate from treatment of 36% is actually lower than the rate of 47% on average typically found in studies of online behavioral health interventions [
In addition, people did not drop out entirely at random. Participants who dropped out during the initial treatment phase had significantly higher rates of visceral anxiety and fear of food at baseline (although there were no other significant differences). Since CBT for IBS typically encourages acceptance of visceral sensations and reduction of behavioral avoidance (especially avoidance of food and food-related social situations), the treatment may have seemed particularly challenging for those individuals. This might represent a population requiring more personal guidance, encouragement, and support from in-person therapy.
A fourth limitation of the study was the inability to statistically establish the temporal precedence of the proposed mediators of change. In the study design, there was no midpoint survey to show that visceral anxiety, catastrophizing, and fear of food changed
A fifth limitation is that the PHQ-9 is a poor measure of depression severity because it only measures symptom frequency and does not take intensity of symptoms into account. For example, at baseline, someone might indicate feeling tired or having little energy nearly every day (scoring a 3), because they are so anergic they can barely get out of bed. By the end of a trial, they might still indicate feeling tired or having little energy nearly every day (scoring a 3) because they still feel chronically fatigued, but they are getting up and going to work every day. The
A sixth limitation is that we did not assess concurrent medication use. However, there is no reason to believe that medication use would have been different across the immediate treatment and control groups.
Finally, the last phase of the trial occurred during the COVID-19 global pandemic. Since all waitlist participants had already been crossed over to the active treatment phase, the 3-month follow-up data may be less reflective of the enduring effects of the treatment and more reflective of the massive social, economic, and personal upheaval the pandemic has caused. Indeed, the end of the treatment phase for all participants coincided with the COVID-19 pandemic’s arrival in the United States. With massive shutdowns and quarantines, it is highly likely that distress increased for all participants. The fact that treatment gains were generally maintained and that participants remained much improved over baseline (except for some recurrence of depression), even in the face of an unprecedented global health crisis, is encouraging.
Despite the limitations, we believe that this study is of significant value. It successfully demonstrated the efficacy of an app that provided CBT for IBS patients. The intervention was not restricted by geography or scheduling constraints, and required no face-to-face contact with a clinician, aspects that dramatically increase the accessibility and portability of treatment. Despite its relatively benign physical profile, IBS can be an extraordinarily debilitating condition. Finding novel ways to disseminate evidence-based, effective treatments remains an important challenge, and Zemedy is a promising and effective way to help those suffering from IBS.
Consent form.
CONSORT-eHEALTH checklist (v 1.6.1).
cognitive behavioral therapy
Depression Anxiety Stress Scale
Fear of Food Questionnaire
gastrointestinal
Gastrointestinal Cognitions Questionnaire
Gastrointestinal Symptom Rating Scale
health-related quality of life
irritable bowel syndrome
IBS Quality of Life Impairment
mobile health
Patient Health Questionnaire-9
randomized controlled trial
Visceral Sensitivity Index
Bold Health provided some funding to pay for recruitment advertisements and participant incentives.
MH substantively designed the content of the intervention, designed and ran the trial, performed most of the statistical analyses, and wrote most of the paper. SM and BD were the research coordinators who oversaw much of the day-to-day administration of the trial, including recruitment, randomization, scheduling assessments, and scoring and cleaning the data. In addition, SM assisted with statistical analyses and drafting the manuscript. OO oversaw the conversion of the CBT protocol into the digital format, coordinating the team of programmers and designers who created the app itself. SW performed the intention-to-treat and mediation analyses, and drafted those sections of the manuscript. All authors reviewed and approved the manuscript.
OO has a financial ownership stake in Bold Health, which developed and markets the Zemedy app. MH, SM, BD, and SW have no conflicts to declare.