Scientific Papers

Reconsolidation of traumatic memories protocol compared to trauma-focussed cognitive behaviour therapy for post-traumatic stress disorder in UK military veterans: a randomised controlled feasibility trial | Pilot and Feasibility Studies

We conducted a parallel group, single-centre feasibility randomised controlled trial with a post-trial qualitative interview study. Randomisation was stratified by (a) diagnosis of simple or complex PTSD (CPTSD), and (b) sex. The trial is registered on 01.10.2019 with ISRCTN reference 10314773. Ethical approval was granted by King’s College London Research Ethics approval reference HR-18/19–11320 on 19.04.2019.

COVID-related changes to the protocol

Following registration of the original protocol, three COVID-19-related changes were made in consultation with the Trial Steering Group, the Data Monitoring and Ethics Committee and the KCL Ethics Committee. These were as follows: Initially randomisation was 1:1 ratio but changed at the recruitment mid-point to a 2:1 ratio favouring the experimental treatment arm. This resulted from COVID-19-related recruitment delays associated with lockdowns and reduced therapists’ capacity in the comparison treatment arm. Recruitment was widened from focusing solely on Northern Ireland to UK-wide veterans and the recruitment period was extended for an additional 6 months. In addition, delivery of both therapies necessarily moved online and the trial was paused for 6 weeks to enable the therapy provider to incorporate online therapy delivery on a secure platform and subsequently all therapies were delivered remotely via videocall. The methods and results presented reflect these changes.

Participants and setting

Inclusion criteria were (1) adults ≥ 18 years, (2) UK military veterans from the Royal Navy, Army, Royal Air Force, (3) a diagnosis of PTSD determined by DSM-5 [2], (4) symptoms causing clinically significant distress or impact on social, occupational or other areas of functioning using the Clinician Administered PTSD scale (CAPS-5) [17] and the International Trauma Questionnaire (ITQ) [18], (5) living or working in the UK.

Exclusion criteria were (1) serving personnel, (2) currently receiving psychological treatment for PTSD, (3) a comorbid DSM-5 mental health or personality disorder sufficiently severe as to intrude upon the participant’s ability to cooperate with treatment, (4) dependence on alcohol, prescription medication or illegal substances, (5) suicidality within the previous month, (6) unable to provide informed consent, (7) self-reported Psychoactive medication changes in the previous 4 weeks, (8) other reason arising from eligibility assessment by Clinical Psychologists such as therapy readiness. The clinical elements of the trial were delivered via Inspire Wellbeing, an all-Ireland third sector organisation holding statutory public health contracts to treat and support people with mental health conditions, intellectual disabilities and addictions. They have extensive experience of working with veterans with complex needs as well as serving military and emergency service personnel routinely, unavoidably exposed to traumatic events.

Participant recruitment and eligibility screening

Recruitment took place across the UK between February 2020 and June 2021. Veterans were informed of the trial through our charity clinical partner, Inspire Wellbeing, and their veteran mental health commissioning organisations, through our public engagement work with UK-wide veteran charities using traditional and online media announcements and through a targeted social media campaign. Potential participants contacted a dedicated PETT study email address or were referred from statutory and third sector veteran support agencies. After signing a GDPR compliant personal data processing consent form they completed the PTSD Checklist for DSM-5 (PCL-5) [19] to screen for eligibility. Veterans with a score ≥ 33 on the PCL-5, indicating probable PTSD, were invited to undergo the informed consent process and collection of baseline data. A PTSD and complex PTSD diagnostic interview was undertaken by a consultant clinical psychologist at Inspire using the Clinician Administered PTSD Scale (CAPS-5) [17] and the ICD-ITQ [18].

Participant safety

Aligned with our research question regarding RTM safety, adverse and serious adverse events were operationally defined, monitored and risk escalation procedures put in place. RTM participants were provided with and regularly reminded of emergency telephone numbers along with the contact details for a trial-funded, but independent, trauma-experienced Clinical Psychologist. An adverse event was defined as a ≥ 10-point increase in the self-report PCL-5 in the interim between the previous therapy session, a 15-point rise from baseline or the maximum score of 80 being reached. Depression severity follow-up data assessed by the PHQ9 [20] were reviewed within 48 h of receipt to identify anyone at risk of self-harm or suicidality.

Randomisation, stratification, and allocation concealment

King’s College London Clinical Trials Unit provided a computer randomisation system. Participants were randomised within 30 days of baseline assessment. Randomisation was stratified based on (1) diagnosis of PTSD or CPTSD and (2) sex. Eleven percent of the UK veteran population are of female sex and their military traumas can be different in origin [21]. Of these, 11% have PTSD with their traumas being different in origin from those of male veterans [22, 23]. We aimed to determine whether our research protocol would also attract female participants to progress equality, diversity, and inclusion. Unique participant IDs were generated and computer randomisation to therapy A or B occurred, and allocation sent to the only unblinded member of the research team and an administrator at Inspire for communication with the participant and allocation of therapist. The unblinded researcher supported the therapists’ data entry, monitored participant safety and had no contact with participants or their research data.

Interventions and delivery

Ten Inspire therapists were invited to undertake professional training to deliver the interventions following completion of the revised Cognitive Therapy Scale [24] and providing current professional accreditation evidence and duration of experience of treating PTSD/CPTSD. We aimed to develop two therapy teams with comparable experience across 5 escalating levels. Level 1 therapists were newly accredited counsellors with limited experience of working with PTSD/CPTSD and competence self-reported across the majority of skills on the revised Cognitive Therapy Scale [24]. In contrast, level 5 had over 10 years post-accreditation experience, rated expert on the revised Cognitive Therapy Scale and had multiple professional accreditations. The two comparable teams were formed by randomly allocating each therapist according to level to join either of RTM or TFCBT training teams. RTM therapists undertook pre-course reading, 40 h over 4 days of face-to-face classroom teaching and 4 h of symptom assessment and therapy delivery on two trauma patients which were observed and assessed for fidelity by the RTM trainer/supervisor and an external assessor from the US research team. TFCBT therapists undertook 24 h of face-to-face classroom teaching aligned to Ehlers and Clark’s cognitive processing model [25, 26] incorporating reflective exercises alongside practical clinical case examples illustrating key intervention strategies. Their competency was assessed as the training progressed. Four therapists in the RTM arm and two in the TFCBT arm demonstrated competence and willingness to deliver the interventions within the trial. All therapies were delivered remotely on a secure online video platform by a single therapist who received therapy-specific clinical supervision within their therapy team.

Experimental RTM

The experimental RTM intervention [27], was delivered in two to four × 90-min sessions with at least one mandatory sleep cycle between sessions. The RTM Protocol is a brief cognitive intervention with minimal and non-traumatising exposure to the original stimulus. The manualised 89-step RTM protocol aims to rewrite the emotional elements of the memory by taking advantage of so-called reconsolidation [27]. Reconsolidation describes the reactivation of long term, otherwise permanent memories, by their evocation in certain contexts [28, 29]. When a memory is reactivated, it labilises, that is, it becomes subject to change. If the circumstances surrounding the memory remain the same, the memory remains unchanged; it is maintained in its current state. If circumstances have intensified, the impact of the memory may become worse; re-traumatization can add to the intensity of trauma memories. If the new circumstance provides evidence that a threat of negative emotional stimulus is no longer relevant, the strength of the affective charge may decrease. RTM was delivered over a 3- to 4-week period from first to final session.

Comparison TFCBT

TFCBT was delivered over up to 18 × 60 to 90-min weekly sessions [26]. The cognitive processing model of PTSD developed by Ehlers and Clark (2000) was purposely used in this study because it displays the largest treatment effect sizes and significant symptom improvement and is widely delivered through IAPT services [25, 26, 30]. TFCBT is focused on identifying the relevant appraisals, memory characteristics and triggers, and behavioural and cognitive strategies that maintain PTSD symptoms. TFCBT was delivered over an 18-week period from first to final session.

Data collection

Data collection took place at baseline (Time (T) 1), and weeks 6 (T2), 12 (T3), and 20 (T4) post-randomisation. Questionnaires were completed by post, telephone or online using Qualtrics. Follow-up data was included if collected 10 days either side of the expected time point. Data was entered onto eCRF database (Elsevier MACRO) hosted on King’s Clinical Trial Unit encrypted server. Participants were offered a £15.00 shopping voucher when returning T2–4 questionnaires.

Primary outcomes

These were feasibility related:

  • Proportion recruited, defined as the number who consented to enter the study over the number who were screened for the study.

  • Proportion randomised, defined as the number who were randomised to a treatment arm over the number who consented to enter the study.

  • Proportion of drop out/research attrition, defined as the number who left the study over those who were randomised to a treatment arm.

  • Completeness of outcome data, defined as the proportion of data which was complete at the 20-week outcome.

Secondary outcomes

Mental health outcome data assessed data quality and was used to detect an effect signal and standard deviation to determine a sample size calculation for an efficacy trial. The anticipated primary outcome for a full trial is PTSD symptoms assessed by the PCL-5 [19]. A score of ≥ 33 is indicative of PTSD diagnosis. The minimal clinically important difference (MCID) for PCL-5 is a reduction in score of 10 points or more from baseline to 20 weeks [19]. The Work and Social Adjustment Scale (WSAS) [31] is a 5-item scale to assess the impact of the person’s mental health on work, home, social and private leisure activities and interpersonal relationships. A higher score is indicative of recovery. The MCID for WSAS is taken as a reduction in score of 8 points or more from baseline to 20 weeks [32]. The Quality of Process of Recovery scale (QPR) [33] assesses mental health recovery by measuring intrapersonal functioning and interpersonal functioning on a 0–88 scale with higher scores indicative of recovery. The Patient Health Questionnaire (PHQ) [20] is used as a screening instrument for depression. The PHQ-9 has a MCID of a reduction in score from baseline to 20 weeks of 5 points or more [32]. The General Anxiety Disorder (GAD 7) [34] screens for anxiety. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate, and severe anxiety, respectively. The GAD MCID is a reduction in score from baseline to 20 weeks of 6 points or more [32]. The EQ VAS [35] assesses perceived health status on a 0–100 visual analogue scale.

Sample size

We took into account recommendations for pilot trials which propose a method for determining an external pilot RCT sample size in order to estimate the sample size for the main RCT [36]. Trials comparing therapy and research attrition rates for TFCBT and EMDR in general PTSD populations found a range 8–58% with a mean of 29% [37]. Informed by these data we proposed screening 180 potential participants for eligibility and randomised 60 participants. See Table 1 for progression criteria relating to sample size.

Table 1 Pre-specified progression criteria to an efficacy trial

Statistical methods

For the primary feasibility outcomes, raw numbers and proportions will be presented. The proportions are presented with the 95% CI. The analysis of the secondary outcomes aimed to estimate the mean and standard deviation for the PCL-5 score at 20 weeks for each treatment group and the mean difference and standard deviation of the in PCL-5 score from baseline up to 20 weeks for each treatment group. This method was repeated for the WSAS, QPR, PHQ-9, GAD-7, and EQ VAS data. Across the secondary outcomes, we present 95% CIs for the differences between arms.

Trial management and oversight

A project management group of all investigators and the research team met on six occasions. The research teams from both King’s College London and Queen’s University Belfast met two-weekly to monitor recruitment, retention, and safety. The Trial Steering Committee comprised a consultant psychologist, a consultant forensic psychiatrist, and a charity representative, all of whom had veteran health expertise. The Data Monitoring and Ethics Committee comprised a consultant clinical psychologist, an independent statistician, a psychological therapist and a charity representative. These committees met jointly on three occasions. Participant safety was discussed at each meeting.

Progression criteria to an efficacy trial

Criteria were agreed with the funder at the application stage according to important scientific trial criteria and strategic funding objectives of the funder (Table 1) using traffic light assessment.

Qualitative study

Online semi-structured interviews aimed to (a) explore veterans’ experiences of joining the RCT, (b) their experiences of research procedures and therapy, and (c) their views on how to improve the research design for future studies with this population. Online semi-structured interviews were used as an adjunct to supplement and add depth to the trial results [38]. An interview guide was developed by the research team informed by current literature on RTM and the objectives of this study and structured into four main parts aligned with the objectives.

Qualitative data collection

Participants who had previously consented to an interview were contacted and participation in this phase advertised in our project newsletter. The sampling framework consisted of three groups: (a) veterans who completed RTM therapy, (b) veterans who completed TF-CBT therapy, and (c) those who did completed neither therapy. The interviews were conducted following the 20-week follow-up and immediately before the study end. Interviews lasted 40–60 min and were conducted via Zoom. The audio-recordings were saved to a King’s password protected laptop and were transcribed using Microsoft Word transcription function.

Qualitative data analysis

The six-step thematic analysis approach by Braun and Clarke was implemented to analyse and identify patterns of meaning [39]. Initial codes were generated and validated in coding teams and applied to remaining transcripts. A thematic map was generated to visually collate the codes under meaningful themes with names and definitions generated.

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