Eligibility criteria {10}
Detailed inclusion and exclusion criteria are listed in Table
1.
Table 1
Detailed inclusion and exclusion criteria
Inclusion criteria |
1 | Age 18–65 |
2 | Meet Rome IV diagnostic criteria for IBS |
3 | A pain intensity score of at least 60 (on a scale of 0–100) |
4 | Frequency of abdominal pain at least 5 out of 10 days |
5 | Informed consent |
Exclusion criteria |
1 | Insufficient proficiency in the Dutch language, or any other circumstances interfering with communication or completing questionnaires |
2 | Psychiatric problems such as psychosis, severe depression, or suicidality requiring immediate treatment |
3 | Ongoing trauma-focused treatment, such as EMDR, trauma-focused Cognitive Behavioral Therapy (tCBT), and Imaginary Exposure (IE) |
4 | Any other medical conditions such as Colitis or Crohn’s disease in which abdominal pain is a key symptom |
5 | Pain in another area of the body which is more prominent than abdominal pain |
6 | Ongoing drug abuse (excluding nicotine or caffeine abuse) interfering with EMDR therapy |
7 | Self-reported pregnancy or planned pregnancy within the next 5 months. Sensations in the abdomen caused by the pregnancy might be difficult to distinguish from the sensations caused by IBS |
Subjects are eligible for participation if they meet Rome IV criteria for IBS and report severe pain intensity at least half of the time. Severity of pain is measured by the self-reported pain intensity score on the Irritable Bowel Syndrome—Severity Scoring System (IBS-SSS). A pain intensity score of 60 or more on a scale of 0–100 is considered to reflect “severe pain.”
The Rome IV criteria [
4] are:
Recurrent abdominal pain, on average, at least 1 day/week in the last 3 months, associated with two or more of the following:
Criteria need to be fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.
Participants are allowed to continue any prior IBS treatment such as medication or a diet as long as they agree not to change these during the trial.
Treatment will be administered by qualified psychologists who have been included in the Dutch legal register for Professions in Individual Health Care (BIG-register) and are at least EMDR Europe accredited level 1 trained in EMDR therapy.
The gastroenterologist establishes whether subjects meet Rome IV criteria for IBS. Afterwards, they complete a short questionnaire comprised of the IBS-SSS (short form) to which this question is added: May we invite you to participate in a scientific study of a new treatment for IBS?
Subjects meeting the initial criteria (pain intensity and frequency) receive, by post, the Patient Information Form packet (PIF) approved by the Medical Ethical Committee. About a week later the principal investigator calls the subject to answer questions that may have arisen and to screen for exclusion criteria. If the subject meets inclusion criteria, does not meet exclusion criteria, and is willing to participate, he or she fills out and signs the consent form included in the PIF and sends it to the principal investigator in the included return envelope.
Interventions
Explanation for the choice of comparators {6b}
So far, no scientific research has been done to study the effect of EMDR on pain in IBS. We choose to compare the intervention group with a wait-list control group. Comparison to an active control group such as gut-directed hypnotherapy or psychoeducation would require a larger sample size than we have the means to carry out. The same restrictions in time and resources prevent us from arranging an inactive control condition.
Intervention description {11a}
EMDR treatment is based on the eight phases of the EMDR standard protocol [
31‐
33]. Listed below are the principal steps in each phase.
1.
History taking: taking history, making a case conceptualization based on the information gathered, and compiling a list of traumatic experiences.
2.
Client preparation: explanation of the theory behind EMDR, the introduction of the eye-movement task and tactile and auditory tasks (buzzers, clicks), answering questions, in general preparing the client for EMDR.
3.
Assessment: the memory that will be processed in the session is decided on. The target image (the most distressing image of the memory) is identified, as well as the principal negative belief, feelings, and sensations linked to the memory. Also, a positive cognition is chosen. Baseline measures are established for the credibility of this positive cognition (Validity of Cognition, VoC), and the amount of stress generated by the target (Subjective Units of Distress, SUD).
4.
Desensitization: taxing working memory while focusing on the target, by applying eye movements, until the SUD score is zero.
5.
Installation: strengthening of the positive belief until it feels true.
6.
Body scan: the therapist asks the client to bring the original target to mind and check for any residual tension in their body. If so, these physical sensations are then targeted for reprocessing.
7.
Closure: consolidation of the positive effects (whether the reprocessing is complete or not), instructions for between sessions and how to reach the therapist when needed.
8.
Reevaluation of treatment effect: takes place at the beginning of each new session, to check whether the SUD of previous targets is still low.
After that another memory from the trauma list is chosen, for which the procedure is repeated from phase 3.
A special kind of target is the flash forward, which does not involve a memory, but an image representing a dreaded event in the future. Interweaves can be used when the reprocessing process is blocked or loops. Extra tasks taxing working memory can be used in case of high-stress levels of abreaction.
In this study, the intervention consists of seven weekly 90-min sessions, which include:
-
An intake in which onset, severity, frequency, and impact of IBS symptoms are explored and an overview is made of all the traumatic events related to the onset and/or maintenance of the abdominal pain or negative experiences with the pain. Both PTSD A criterion events such as rape or car accident and adverse events that are not life-threatening such as bouts of severe abdominal pain or instances of (near) defecation in public are included in the overview. Based on the acquired information, a case conceptualization is made, from which the memories to be processed are selected. This concludes phases 1 and 2 of the EMDR standard protocol.
-
Six sessions of EMDR lasting 90 min each in which phases 3 to 8 of the EMDR standard protocol [
31‐
33] are applied to the selected memories. In addition to the customary sets of rapid eye movements, tactile and auditory input (buzzers and beeps) may be applied to optimally tax working memory. During the EMDR sessions, the therapist will direct extra focus/attention to physical sensations, usually abdominal sensations. If relevant, a flash forward will be desensitized. Interweaves will be applied if necessary. Successful desensitization is defined as the reaching of SUD = 0 (Subjective Units of Distress; the recollection of the event no longer causes the subject any distress). If severe abdominal pain remains after having processed all relevant targets, the pain itself will become the focus of the next EMDR session. Treatment is ended either after six 90-min sessions, or when all relevant memories have been successfully desensitized.
Treatment takes place face-to-face. However, if necessary due to quarantine during the COVID-19 pandemic, it can also be offered online via video consultation. Although as yet little is known about the effectiveness of online EMDR treatment for PTSD, so far results are promising that effects may be similar to real-life EMDR treatment [
34].
Criteria for discontinuing or modifying allocated interventions {11b}
With acquiring new information during sessions, the case conceptualization can change a little, which in turn can change the selection of memories to be processed. The EMDR treatment in itself will not be altered.
Patients are free to withdraw from partaking in the study at any time. The research team can decide to remove a patient from the study if.
1.
There are serious medical reasons.
2.
The subject fails to complete the questionnaire(s) during the first period of measurements.
3.
The subject fails to appear at a treatment session more than twice (without notice).
4.
The subject’s non-cooperation seriously hinders treatment.
5.
Subject meets an exclusion criterion along the way (e.g., becomes pregnant or an intestinal disease is diagnosed).
6.
There are persistent serious side effects.
Like all studies involving human subjects, we are required to report serious adverse events as defined by the Central Committee on Research Involving Human Subjects (in Dutch: CCMO, Centrale Commissie Mensgebonden Onderzoek).
No serious adverse effects have been found in studies of EMDR in diverse populations. Some discomfort—both physical and psychological—both during sessions and in the first 4 days after an EMDR session is not unusual. As this is part of the psychological process of processing negative memories, this is no cause for discontinuing the intervention.
Any unexpected adverse effects will be discussed within the research team, which includes two EMDR Europe registered EMDR consultants with extended expertise. Depending on the outcome of this deliberation, steps will be taken to reduce the adverse effects. If necessary, participation in the study will be temporarily interrupted. If the adverse effects persist, participation in the study will be discontinued.
Strategies to improve adherence to interventions {11c}
Prior to the inclusion of a participant, an explanation about EMDR therapy is given in the Patient Information Form and, if desired, questions are answered during the telephone call in which exclusion criteria are checked. Again, later, during the intake subjects are informed thoroughly about what to expect during and after an EMDR treatment session. This increases motivation and adherence to the therapy once treatment has started.
Beforehand, trial therapists are required to demonstrate their competence in applying the treatment. As yet, there are three trial therapists, but more may be added later. To ensure treatment quality and adherence to the EMDR standard protocol, the therapists receive monthly supervision sessions by the EMDR consultants based on the EMDR treatment sessions videotaped during the study. Furthermore, weekly session checklists are viewed by the consultants to closely follow the EMDR process. Any questions by the therapists will be answered before the next session. Also, every session is videotaped to enable regular fidelity checks. Fifteen percent of all recorded sessions will be reviewed for treatment fidelity using the Treatment Integrity Checklist for EMDR. Fidelity checks will be done at random, by the last author (YvR), who is an EMDR Europe registered EMDR consultant with extended expertise.
Relevant concomitant care permitted or prohibited during the trial {11d}
Concurrent treatment for psychotrauma is an exclusion criterion. Upon entering the study, participants agree to refrain from starting other treatments (medication, nutritional supplements) or behavioral changes (e.g., diet) aimed at the IBS symptoms.
Treatments and diets that are already part of the patients’ customary regimen can be continued. We ask subjects to report any changes in their prescribed medication. At three measurement moments, subjects are explicitly asked about their current medication use.
Provisions for post-trial care {30}
Subjects from both the intervention and wait-list control group will after the end of the study meet with the principal investigator to determine if there is (still) a wish or need for treatment for the IBS symptoms. If so, they are offered treatment appropriate to their current situation, provided that this can be offered by the Department of Clinical Psychology of the Diakonessenhuis. In some cases, referral to mental healthcare may be the best course of action.
No harm is expected to occur from participating in the study and the medical ethical committee has agreed to grant an exemption for an insurance for the participants of the study. The hospital, however, has, as required by law, a liability insurance for compensation of those who suffer from harm incurred in the hospital.
Outcomes {12}
The primary outcome of this study is the intensity of abdominal pain. As the intensity of abdominal pain in IBS can vary greatly from day to day, we have chosen to pose the same question each day for 2 weeks. Participants answer the question: “How much did you suffer from abdominal pain during the last 24 h?”. The subject’s answer is given on a 21-point Likert scale (0 = no pain, 10 = worst pain imaginable, half points possible).
In addition to the primary outcome measure (abdominal pain), we pose four other diary questions at the same time, during the same period, with the same 21-point Likert scale. Based on their statements at inclusion about their principal IBS symptoms, we ask about their top two symptoms (abdominal pain excluded): “How much did you suffer from (complaint) during the last 24 h?” (0 = not at all, 10 = extreme suffering, half points are possible). These symptoms could be frequently occurring IBS symptoms such as diarrhea, constipation, and bloating, but they can also be more idiosyncratic such as dizziness. We also ask about the hindrance subjects have experienced from their IBS symptoms when engaging in everyday activities. Based on their statements at inclusion about the two- valued activities that are most impeded by the IBS symptoms, we ask for every one of these activities: “How much hindrance have you experienced from your IBS symptoms when engaging in this activity?” (0 = no hindrance at all, 10 = made completely impossible; half points possible). Activities most likely to be impeded by IBS symptoms are working, doing sports, going out for dinner, and going out (dancing, theatre, etc.).
The 14-day-sequence of these 5 “diary questions” is administered at inclusion, 8 weeks after inclusion (for the intervention condition this means after treatment), and at follow-up (20 weeks after inclusion, 3 months after treatment).
In addition to the diary questions, we administer several questionnaires, the purpose of which is to describe the population and to either confirm or disconfirm the results of the diary questions. They also enable comparing outcomes with those of other studies. The questionnaires are administered on the last day of every 14-day-sequence of diary questions.
The questionnaires administered are:
1)
IBS-SSS (Irritable Bowel Syndrome—Severity Scoring System) [
35].
The first part of this questionnaire consists of 5 questions regarding the frequency and intensity of pain, the intensity of bloating, satisfaction with bowel movements, and the impact of IBS on the subject’s life in general. The answer type varies per question (Visual Analog Scale 1–100 or a specific number). Scores can range from 0 to 500 with higher scores indicating more severe symptoms (75–175 mild, 175–300 moderate, > 300 severe). The IBS-SSS severity score is recognized by the Rome Foundation as an appropriate measure for assessing changes in research on treatments [
36]. A decrease of 50 points is considered a clinically relevant improvement.
Part two of the IBS-SSS consists of 5 questions that explore the nature and quality of the symptoms. In this study, only the localization of abdominal pain is addressed.
2)
IBS-QOL (Irritable Bowel Syndrome—Quality of Life measurement) [
37]
This questionnaire measures the impact of IBS on quality of life. It contains 34 statements covering the following 8 areas: Dysphoria, Interference with Activity, Body Image, Health Worry, Food Avoidance, Social Reaction, Sexual, and Relationships. Subjects are asked to indicate to what extent each of these statements applies to them on a 5-point Likert scale (1 = not at all, 5 = very much). The individual responses to the 34 items are summed and averaged for a total score and then transformed to a 0–100 scale for ease of interpretation with higher scores indicating better IBS-specific quality of life. In addition to the total score, a scale score can be calculated for each of the 8 areas mentioned. Distribution of the IBS-QOL is managed by the Rome Foundation. Psychometric properties are well established [
38].
3)
AR (Adequate Relief Question)
This is one question: “In the last 7 days, have you had adequate relief of your IBS symptoms?” The answer can be yes or no. The Rome Foundation accepts and recommends this outcome measure in RCTs [
39,
40]. In this study, AR is included as an outcome measure to allow comparison of our results to those of studies using this recommended outcome measure.
Other questionnaires, not used as outcome measures, but solely administered to describe the population are:
a)
LEC-5 (Life Events Checklist for the DSM-5) [
41]
This questionnaire is a self-report measure designed to screen for potentially traumatic events in a respondent's lifetime. It describes 17 (A criterion) events, and subjects are asked to indicate whether they have experienced such an event and in what way (happened to me, witnessed it, learned about it, part of my job, not sure, doesn’t apply). There is no formal scoring protocol or interpretation per se, other than identifying whether a person has experienced one or more of the events listed. The LEC-5 in combination with the PCL-5 can be used to screen for PTSD.
In this study, the LEC-5 in combination with the PCL-5 is used to screen for PTSD criteria.
b)
PCL-5 (PTSD Checklist for the DSM-5)
This self-report questionnaire consists of 20 items concerning the 20 DSM-5 symptoms of PTSD. For each symptom, subjects are asked to indicate on a Likert scale to what extent they have suffered from it in the past month (0 = not at all, 1 = a little bit, 2 = moderately, 3 = quite a bit, 4 = extremely). A total symptom severity score (range 0–80) can be obtained by adding the scores of the 20 items together. DSM-5 severity scores for the individual symptom clusters can be obtained by summing the scores of the items of a particular cluster. The PCL-5 can be used in combination with the LEC-5 (see below) as a screening tool for PTSD. An indication for a PTSD diagnosis can be obtained by counting any item with a score of 2 (moderate) or higher as a symptom that is present. Then the DSM-5 diagnostic calculation rule is followed to ascertain whether the required criteria are met: a minimum of 1 B-symptom (questions 1–5), 1 C-symptom (questions 6–7), 2 D-symptoms (questions 8–14), and 2 E-symptoms (questions 15–20). The PCL-5 can also be used to determine the course of PTSD symptoms. Results from the USA with the previous version of the PCL (PCL for DSM-IV) suggest that a 5–10-point change indicates a reliable change and a 10–20-point change indicates a clinically significant change [
42].
In this study, the PCL-5 is used to assess the severity of PTSD symptoms.
Diary questions and questionnaires are administered digitally, using an ISO 9001-certified online tool. Subjects receive an e-mail containing a link to the diary questions or the questionnaire, which they then can fill out.
Sample size {14}
Several factors have influenced the sample size in this study: setting, method of analysis, and the estimate of comparability with previous scientific research.
As the study is conducted as part of the curriculum of a training course taken by the principal investigator, both time and resources are limited. Our aim is to demonstrate a clinically relevant treatment effect regarding the primary outcome measure with a limited sample size.
The design of our study enables us to analyze our primary outcome data (pain score diary) using a linear mixed effects models analysis. Sample size was computed using the online statistical calculation program GLIMMPSE (General Linear Mixed Model Power and Sample Size):
https://glimmpse.samplesizeshop.org/#/ using an alpha of 0.05 and a desired minimum power of 0.80.
The most important estimated value required by the GLIMMPSE program is the expected effect size. Since a study on the effect of EMDR on abdominal pain in IBS has never been done before, a search was made for comparable research. A review on EMDR treatment for chronic pain found large effect sizes [
22]. The EMDR for phantom limb pain study design is most comparable to our study design [
28]. Based on this study, a remarkably large effect size d of 1.22 was calculated. On entering this effect size, GLIMMPSE calculated that a sample size of 12 should be sufficient. However, when a demonstration of an average effect size is wanted, a sample size of 24 is needed. This sample size is adequate to analyze the primary outcome measure daily pain scores using a linear mixed effects model. In addition, this sample size is also expected to be adequate to analyze the secondary outcome measures from the standardized questionnaires (measures taken only three times in total) with LME models. Taking drop-out into account we decided to include a maximum of 34 participants.