Aim of study
Our present study was undertaken to verify the effectiveness of the Internet-based Cognitive Behavioral Therapy with Real-Time Therapist Support Via a Video Conference (vCBT) which we have carefully challenged. This study was designed as a prospective randomized open-labelled pilot trial with two parallel 16-week intervention groups: a vCBT group that also received treatment as usual and a continuing TAU group alone (Figure 1).
Our hypothesis considers that the vCBT group will show more effectiveness than the continued usual care group in both pain intensity and other pain-related outcomes. In previous studies, CBT has shown improvement over usual care alone in disability of daily life and catastrophizing thought due to pain. However, the degree of effectiveness is insufficient, and we want to demonstrate greater effectiveness using this program.
Participants and recruitment
As all participants will continue to be treated by their general practitioners, participants will be required to obtain permission from them prior to study enrolment. Inclusion and exclusion criteria show Participant recruitment was conducted through posters and leaflets placed at medical institutions in Chiba Prefecture and through web-based and newspaper advertisements from April 2018 to November 2019. Further, this study will be announced to outpatients in the Department of Orthopedics and Pain Anesthesiology in Chiba University Hospital.
Eligibility procedure for participation and diagnosis
Participants are requested to keep a record of pain assessment for a week and to submit this record at the initial visit. To determine eligibility, participants will visit a doctor and receive an explanation about the risks, benefits, and expected commitment to the study. Finally, they will be requested to provide informed consent. After obtaining informed consent, a screening test based on inclusion and exclusion criteria will be conducted by a clinical psychologist or nurse (Table 1).
Randomization and case registration
After completing the baseline assessment, eligible participants will be randomly assigned to either the TAU group or the vCBT group, using the minimization method, ensuring a balance in pain scores and gender. As the allocation adjustment factor, the pain score on NRS is allocated at more than 6.3 or less19.
Description of the intervention
Both usual care and vCBT groups will undergo 16 weeks of intervention. In both groups, patients answer questions consisting of primary and secondary outcomes at 1 (baseline), 8 (middle), and 16 (post) weeks after the intervention, and mail to the researcher.
Internet-based CBT for chronic pain program
Internet-based CBT programs for chronic pain generally consist of 8–12 intervention sessions. Contents are usually psychological education for pain, case formulation for searching the vicious circle of pain, cognitive reconstruction and relaxation as a self-control skill over pain, etc. We have added four experimental sessions, including one based on the latest knowledge about brain science and psychology, to this program to further improve its impact8 (Table 2). We have incorporated four new sessions that have not been used in CBT protocols for chronic pain so far.
Tactile attention-shift training(session4); The patient notices the “attention bias,” given to their painful body parts and needs to correct the attention imbalance. There is a hypothesis that pain can be relieved through promoting secretion of oxytocin through the therapist’s gentle touching of the affected body part. This is called Science Touch and suggests relief of chronic pain26. Attention shift training occurs while paying attention to the therapeutic effect of “touching.” It takes practice to make it possible to freely shift attention from the painful body part to the part without pain.
Memory work using the peak end rule(session10); Chronic pain patients tend to regard a pain experience as a much stronger pain experience than in reality, because pain memory acts as a traumatic memory. Kahneman et al. showed in empirical studies that unpleasant experiences like pain are memorized as the average of the strength of the pain peak and the strength of the end. He suggests that the average of an event’s most unpleasant impression and best impression will remain as memories25. However, for chronic pain patients, intense pain experiences create strong impressions such that the good impression made when the pain is relieved is considered unclear. Therefore, the average of impressions concerning pain is high and is preserved as an intense pain experience. It is expected that pain will be relieved by recollecting the memories of intense pain in detail and rewriting them to objective memory.
Sharpening behavioral image training (session11); This has been applied to body image training used in sports science or rehabilitation medicine after stroke20,21. Patients practice until they can clearly imagine moving their painful body part. Fixing the visual image into memory may increase brain plasticity and lead to recovery of chronic pain.
Video feedback including mirror therapy(session12);In mirror therapy used as treatment for phantom limb pain22, the patient observes movement of the healthy side as reflected in the mirror. Through this visual recognition, the brain understands as if it is the amputated side that is moving, and the pain will be alleviated23,24 If the chronic pain is regarded as a state in which sense and motor contact to the brain is severely disconnected as with phantom limb pain, it is expected that the pain will be alleviated by continuing to observe the video image where the patient's own painful body part is moving.
The CBT intervention will consist of 16 weekly 50-minute sessions using the internet video conference system. We developed the manual based on the existing published resources27, as well as on materials we used in a prior study for anxiety disorder. In this study, we adopt Cisco WebEx as the internet conference system. This system has acquired ISO 27001 certification. Countermeasures against unauthorized access, information leakage, etc. have been taken, and safety problems are also being cleared. If the therapist or the participant finds it impossible to continue due to adverse events, etc., interruptions of up to 30 days can be made only once in all sessions.
The usual care group requires regular visits at least once every eight weeks, with or without drug therapy at the start of study participation.
The therapist should be medically qualified, such as a doctor, nurse, clinical psychologist, mental health care worker, and have finished the basic CBT training by the CHIBA-IAPT, workshop of the Anxiety Society, or the equivalent. In addition, the therapist should have experience implementing CBT under supervision. The therapist will video record every session during the intervention period and will manage the quality of CBT through supervision at appropriate intervals.
We will assess a variety of participant baseline characteristics, including gender, age, education, marital status, employment status, age at pain onset, and duration of pain. Moreover, treatment history will include the names of medications to which the participant has exhibited resistance, current treatment (medication and others) at baseline, other prior treatments, and all changes in conventional treatment throughout the study period.
The primary outcome will be the change from baseline to week 16 as indicated by the NRS score. NRS is a self-rated questionnaire and measures pain intensity on a 0-10 scale (0 = nothing to 10 = severe). Patients keep a pain diary every day. They record (1) maximum pain throughout the day, (2) minimum pain, (3) normal pain as an integer and calculate the weekly average for each pain on the session day (each NRS score = sum total of 1-week NRS score / 7). Numerical values obtained by averaging the values in (1), (2), and (3) are taken as the main evaluation items comprising the composite value of NRS.
Secondary outcomes will be the change from baseline to week 8 in addition to intensity of each pain as indicated by NRS. Catastrophic perception of pain will be measured with the Pain Catastrophizing Scale (PCS)28. Degree of daily life impairment will be measured with the Pain Disability Assessment Scale (PDAS)29. The Clinical Global Impression of Change scale (CGI-C) is used to evaluate the therapeutic effect caused by the therapist. EQ-5D is the most commonly used scale worldwide for calculating quality-adjusted life years (QALYs), which we will use for the assessment of economic evolution of medical technology30. Depressive symptoms will be assessed with the Patient Health Questionnaire-9 (PHQ-9),31and Beck Depression InventoryⅡ(BDI-Ⅱ). Anxiety will be measured with the Generalized Anxiety Disorder scale (GAD-7)32. For assessing the satisfaction of the treatment, the Client Satisfaction Questionnaire (CSQ-8) will be used. The assessment items were set based on IMMPACT II “Assessment of Chronic Pain” recommended by the International Pain Society33.
With reference to previous studies34,35 , we assumed that the group difference in NRS variation is 1.67 and the standard deviation is 1.8; the number of subjects was determined by setting the detection power to 80% and the two-sided significance level to 5% in the t test. As a result, the number of subjects required per group was estimated to be 20.
Statistical analysis and reporting of this trial will be conducted in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines. Baseline variables will be compared using the Fisher’s exact test for categorical outcomes and the unpaired t-test for continuous variables.
For the primary analysis comparing treatment effects, the least-squares means and their 95% CIs will be estimated by analysis of covariance (ANCOVA) with the change in NRS composite score at week 16. This ANCOVA model will take into account the variation caused by treatment effects, and the gender and baseline NRS scores (³ 6.3 and < 6.3) will be entered as covariates. As a sensitivity analysis, we show the transition over time of the NRS scores of each group, confirm the time course measurement data using the linear mixed effect model, and confirm that it is not significantly different from the covariance analysis result.
All comparisons are planned, and all p-values will be two-sided. P-values < 0.05 will be considered statistically significant. All statistical analyses will be performed by using SAS V.9.4. (SAS Institute, Cary, North Carolina, USA).
Patient and Public Involvement
Patients or the public are not involved in the design of the study, and will not involve in recruitment and conduction.
Individual results will be collected by a self-writing questionnaire, so that each participant can know changes in their own intervention effects. The degree of satisfaction with the intervention will be assessed by the participant themselves using CSQ-8 (client satisfaction questionnaire), which is composed the 1-4 (bad-very good) Likert method. The final research results will be disseminated to study participants on request.
Ethics and Dissemination
This study will be conducted under the approval of the Institutional Review Board of Chiba University Hospital (approval ID number: G29049). In addition, the Clinical Research Ethics Review Committee will continuously examine whether this test is properly implemented at least once a year. The trial registration number is UMIN000031124.
The patients who wish to participate in this study will be informed of the study objectives and asked again if they are willing to participate. Each patient will be informed that participation is voluntary, and that full anonymity will be provided. Each participant will then be required to provide written informed consent for their participation in this study.
An adverse event could consist of any unfavorable and unintended sign, symptom, or disease temporally associated with this interventional study, whether considered related to the intervention of this study. All adverse events will be reported, and serious adverse events will be immediately reported to the Institutional Review Board of Chiba University Hospital in addition to being registered with the hospital risk management system. Moreover, an independent data monitoring committee will accurately verify detailed records of the clinical study’s progress, critical efficacy variables, and safety data, and recommend the sponsor to continue, modify, or terminate the study accordingly.