Comparison of the effectiveness of a tailored cognitive behavioural therapy with a supportive listening intervention for depression in those newly diagnosed with multiple sclerosis (the ACTION-MS trial): protocol of an assessor-blinded, active comparator, randomised controlled trial

The aim of the tailored intervention is to significantly decrease levels of depression (primary outcome), anxiety (secondary outcome) and fatigue and pain impact and see improvements in levels of quality of life, fatigue and pain impact, sleep difficulties, MS illness acceptance, active coping skills, social support and resilience (tertiary outcomes). The tailored CBT intervention is derived from Beck’s cognitive theoretical model for the treatment of depression in adults [28]. Table 1 provides an overview of the modules included in the tailored CBT intervention.

SL includes listening skills based on the theory and counselling technique of Carl Rogers [29]. Core listening skills such as paraphrasing, reflecting, summarising and asking open-ended questions are employed. The aim is to provide the participants the opportunity to talk and express themselves in a non-judgmental, safe environment in which they experience empathy from the therapist and feel listened to. Sessions in the SL group are not structured. Participants can choose topics to discuss with their psychologist which they think are currently relevant to them. Figure 2 displays the SPIRIT schedule of enrolment, interventions and assessments.

Therapists will be registered clinical psychologists and registrars with training in CBT. All therapists will complete a 2-day workshop during which they will receive training in the two therapy techniques, with a day devoted to each of the CBT and SL interventions. All therapists will follow strict manualised protocols under the supervision of the trial manager.

Standardisation of the intervention will be achieved by (1) use of a detailed intervention protocol which includes a therapist and client manual; (2) external monitoring of protocol compliance with routine feedback, through weekly supervision by the trial manager with the treating psychologists; (3) a protocol reminder system on our web-based data entry and management tool; and (4) a Data Safety and Monitoring Committee (DSMC) who will review protocol compliance. The DSMC will comprise an independent psychologist, neurologist and statistician who will be in contact with the principal researcher and trial manager.

All intervention sessions will be recorded and used in supervision to provide feedback to therapists and to ensure treatment fidelity. We aim to take a 25% sample of intervention sessions for those in the CBT and SL groups from participants who agree to be recorded based on a random sample generated from an algorithm that takes into account session number, therapist and patient gender. Quality of CBT and SL administered will be assessed using the Cognitive Therapy Rating Scale [30] and a Supportive Listening Rating Scale. In addition, therapists in each condition will be asked to keep a self-reported fidelity checklist of all sessions.

The primary outcome is the percentage of participants achieving the clinically meaningful change of 10 points or more on the BDI-II between baseline and post-intervention in the CBT intervention. Level of depression will be measured with the BDI-II.

Secondary outcomes are the magnitude of change between baseline and 20 weeks on the BDI-II in the CBT intervention with the level of depression measured with the BDI-II and the magnitude of change between baseline and post-intervention on the STAI. Level of anxiety will be measured with the STAI.

Tertiary outcomes are the magnitude of change between baseline and post-intervention on fatigue and pain impact, MS-related quality of life, sleep quality, MS diagnosis acceptance, active coping styles, resilience and perceived social support in the early CBT intervention. Fatigue impact will be measured with the Modified Fatigue Impact Scale-5 item version (MFIS-5) [31]. Pain impact will be measured using the 6-item Pain Effects Scale [31]. Sleep quality will be measured with the Pittsburgh Sleep Quality Index [32]. MS-related quality of life is measured using the 54-item MS-related quality of life measure [33]. Coping styles will be examined using the 66-item Ways of Coping questionnaire [34]. Acceptance of MS illness will be measured using the 10-item Acceptance of Chronic Health Conditions Scale [35]. Level of resilience will be measured with the 33-item Resilience Scale for Adults [36], and Perceived Social Support will be measured using the 12-item Scale of Perceived Social Support [37].

The Therapeutic Alliance Questionnaire [38] will be given to participants at each session, and they will be asked to complete and place it in an envelope which will be given to the therapist the following week. At post-intervention we will ask participants to complete a Therapy Satisfaction Questionnaire to provide information about the acceptability of the CBT intervention.

Participants will be asked to provide serum samples at baseline, post-intervention (8 weeks) and at 20 weeks follow-up. Additional consent for their use in future related research will be obtained.

We will collect test-retest reliability data for BICAMS from all participants enrolled in the trial. Participants will complete the BICAMS at the baseline assessment and again 1 week after this and prior to commencing their first therapy session. Additional consent for this data to be used in future related research will be obtained.

The current study is powered for the primary outcome of the proportion of patients who achieve a clinically significant change of 10 points or more on the BDI-II between baseline and post-treatment in the CBT intervention compared to those receiving the SL intervention. Based on pilot data by Kiropoulos and colleagues [2], the current study will aim to recruit 30 participants in each treatment arm (CBT and SL). The pilot results also revealed that 33% of newly diagnosed individuals screened did not meet eligibility to participate in the trial. Therefore, the current study will aim to screen 90 patients newly diagnosed with MS across three MS clinics in three hospital sites and via advertisements in order to obtain a total sample size of 60. This number will yield 90% power using an α = 0.05 threshold to observe a conservatively estimated 45% difference in proportion of patients achieving a favourable primary outcome. The sample size has also been inflated for drop-outs throughout the 20-week follow-up study.

The primary outcome analysis will be an intention-to-treat between-group comparison of the proportion of patients who achieve a clinical and meaningful change of 10 points or more on the BDI-II between baseline and post-intervention adjusted for baseline depression severity using a logistic regression model. Baseline characteristics will be presented by randomised group without formal statistical tests. Secondary and tertiary outcome analyses will be undertaken using appropriate regression models adjusted for baseline depression severity. Longitudinal changes will be examined using regression models. No formal interim analyses for either efficacy or safety are planned, but safety outcomes will be continuously monitored.

Participants will be asked to record service use including all types and duration of hospital admissions, frequency of outpatient hospital appointments, MS-related community service use, anti-depressant and anti-anxiety medication use and cost and paid and unpaid work using the Client Service Receipt Inventory [39]. Health-related quality of life data and quality-adjusted life years (QALYs) will be assessed using the health-related quality of life measure (EuroQoL-5D) [40].

The study will be co-ordinated by a trial manager who will be a clinical psychologist. Trial monitoring and management will be undertaken by (1) a steering committee who will meet once a year to discuss the overall conduct of the trial and will include the lead investigator and key investigators from the recruitment sites, the trial manager and the statistician; (2) a management committee who will meet fortnightly to monthly to discuss recruitment issues and will include the trial manager and the key investigators from the hospital sites; and (3) safety monitoring, as performed by the independent DSMC who will provide advice regarding the safety of the trial to the steering committee and will consist of a clinician, a psychologist and an independent statistician. We will continuously monitor serious adverse events. All adverse events will be prospectively classified as serious or not serious. An independent clinical adjudication committee adjudicates all serious adverse events for this trial for subsequent reporting to the DSMC. In the unlikely case of an adverse event, this will be documented by the principal researcher and trial manager. Precautions have been taken to reduce the likelihood of adverse events occurring such as the exclusion of patients who are acutely suicidal or severely depressed. The interventions are delivered by clinical psychologists or registrars under the weekly clinical supervision of the trial manager. In the case of any adverse events as a result of taking part in either of the interventions, participation in the trial will be discontinued. Serious adverse events will be reported to the ethics committee. Any adverse events will be reported in the trial paper.

The end of the study is defined as the last data collection during the last 20 weeks follow-up visit from the last participant after the CBT or SL intervention, whichever comes last.

Access to participant data will be restricted to the principal researcher and appropriate study staff as needed. All laboratory specimens and questionnaire forms will be identified using unique participant ID numbers to maintain participant confidentiality. All records including the serum and saliva samples will be kept in secure storage areas with limited access to study staff only. Personal data and anonymised data files will be stored in locked filing cabinets for hard copies and in a secure online database housed on the University of Melbourne secured server with access via password-protected computers by study staff only. All study documentation will be kept for a minimum of 5 years from the protocol-defined end-of-study point in the University of Melbourne archive. All documentation will be destroyed after this date.

Adherence to the CBT intervention will be defined as attendance of the baseline assessment session and attendance and completion of at least four CBT sessions with a psychologist. We will also monitor patient adherence to the CBT intervention through completion of a patient satisfaction questionnaire at the 8 weeks post-assessment. Participant drop-out and reason will be recorded.

Participants will have the option to withdraw at any time during the study period of 5 months. The participant will need to request this formally, and the reason for withdrawing from the study will be recorded by the trial manager. Participant data collected prior to the withdrawal will be used with the permission of the participant. A participant can be withdrawn by the chief investigator should the need arise throughout the study period, and this will also be recorded.

Patients have been involved in the development of the research question and the prioritisation of depression and related factors in the newly diagnosed period as a subject for research. In our pilot trial, patients were involved in a semi-structured qualitative interview where they gave feedback about the content of the tailored CBT intervention and their experience of participating in the trial using the tailored CBT intervention manual [2]. Patients provided feedback about the feasibility, usefulness, appropriateness and content of the tailored CBT intervention [2]. We will send all participants a report describing the findings and their implications.