A Brief GAmeplay Intervention for NHS ICU Staff Affected by COVID-19 Trauma (GAINS Study) (GAINS)

• ClinicalTrials.gov Identifier: NCT04992390
• Recruitment Status: Completed
• First Posted: August 5, 2021
• Last Update Posted: September 8, 2023
• Sponsor: P1vital Products Limited
• Collaborators: Wellcome Trust; Uppsala University; Intensive Care Society; University of Nottingham
• Information provided by (Responsible Party): P1vital Products Limited

Study Description

Brief Summary:

Intensive care unit (ICU) staff are frequently exposed to traumatic events at work (e.g., witnessing patients die), amplified by the COVID-19 pandemic. A significant proportion experience intrusive memories of these events that pop suddenly into mind: these imagery-based memories can disrupt functioning and contribute to posttraumatic stress disorder. Previous research has shown that a brief behavioural intervention can reduce the number of intrusive memories after a traumatic event. In this study we aim to optimise a brief digital intervention to help reduce the number of intrusive memories experienced by ICU staff (primary outcome). We will explore if it can improve work functioning and wellbeing (secondary outcomes). We will recruit approximately 150 ICU staff with intrusive memories of events experienced during the COVID-19 pandemic.

The study is funded by the Wellcome Trust (223016/Z/21/Z).

Condition or disease	Intervention/treatment	Phase
Intrusive Memories of Traumatic Event(s)	Behavioral: Brief digital imagery-competing task intervention	Not Applicable

Detailed Description:

A statistical analysis plan will be prepared prior to the first interim analysis for the outcomes that will guide study optimisation, i.e., primarily the primary outcome.

A second statistical analysis plan will be prepared prior to the end of the study, to outline the standard (frequentist) statistical approaches that will be used to analyse the primary, secondary and tertiary data.

Regular monitoring will be performed by P1vital Products to verify that the study is conducted and data are generated, documented and reported in compliance with the protocol, GCP and the applicable regulatory requirements.

Quality assurance representatives from the Sponsor may carry out an audit of the study in compliance with regulatory guidelines and relevant standard operating procedures.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised Optimisation Study of a Brief Digital Imagery-competing Task Intervention to Support NHS ICU Staff Experiencing Intrusive Memories of Traumatic Events From Working in the COVID-19 Pandemic
• Actual Study Start Date: August 24, 2021
• Actual Primary Completion Date: May 30, 2022
• Actual Study Completion Date: June 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Immediate intervention arm; Immediate access to the brief digital imagery-competing task intervention plus symptom monitoring for 4 weeks including completing a daily count of the number of their intrusive memories in week 4 (primary outcome).	Behavioral: Brief digital imagery-competing task intervention; First session guided by a researcher: A memory cue followed by playing the brief digital imagery-competing task with mental rotation instructions. Option to engage in self-administered/guided sessions after the first session and record their intrusive memories (symptom monitoring).
Experimental: Delayed intervention arm; Usual care for 4 weeks including completing a daily count of the number of their intrusive memories in week 4 (primary outcome), followed by access to the brief digital imagery-competing task intervention plus symptom monitoring for 4 weeks.	Behavioral: Brief digital imagery-competing task intervention; First session guided by a researcher: A memory cue followed by playing the brief digital imagery-competing task with mental rotation instructions. Option to engage in self-administered/guided sessions after the first session and record their intrusive memories (symptom monitoring).

Outcome Measures

Primary Outcome Measures :

1. Number of intrusive memories of traumatic event(s) [ Time Frame: Week 4 (both arms) and Controlling for Run in week (both arms) ]
   Number of intrusive memories of traumatic event(s) recorded by participants in a brief daily online diary for 7 days.

Secondary Outcome Measures :

1. Number of intrusive memories of traumatic event(s) [ Time Frame: Run-in week (immediate intervention arm) , week 4 (both arms) and week 8 (delayed intervention arm) ]

   Number of intrusive memories of traumatic event(s) recorded by participants in a brief daily online diary for 7 days.

   Total number of intrusive memories reported in Week 4 compared to baseline for the immediate intervention group and Week 8 compared to Week 4 for the delayed intervention group (within-group comparisons).

2. Intrusive memory ratings [ Time Frame: Baseline, 4 weeks and 8 weeks ]
   The 9-item questionnaire assesses a number of intrusive memories characteristics. These characteristics include frequency (7-point categorical response from 'never' to 'many times a day); distress (0=not at all to 10=extremely); disruption to concentration (0=not at all to 10=extremely); interference with what you were doing (how much (0=not at all to 10=extremely) and for how long (6-point categorical response from '<1min' to '+60mins')); impact on work functioning (0=not at all to 10=extremely) and in what ways (open text response)); impact on functioning in other areas of life (how much (0= not at all to 10 = extremely) and in what ways (open text response)).
3. Impact of Event Scale-Revised (IES-R) [ Time Frame: Baseline, 4 weeks and 8 weeks ]

   This 22-item questionnaire assesses subjective distress after a traumatic event (with reference to the events for which participants are taking part in the study).

   Items are rated for how distressing they have been during the past 7 days on a 5- point scale ranging from 0 ("not at all") to 4 ("extremely"). Scores are calculated for the intrusion, avoidance and hyperarousal subscales and total score. We will analyse total score (mean of all 22 items) and subscales separately (mean of items in each subscale).

4. PTSD Checklist for DSM-5 (PCL-5) 4-item version [ Time Frame: Baseline, 4 weeks and 8 weeks ]

   This shortened 4-item version of the PCL-5 assesses symptoms of PTSD over the last month.

   Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). Total score ranges from 0 to 16 (cut-off for possible PTSD is 10 or above).

5. Sleep Condition Indicator (SCI) [ Time Frame: Baseline, 4 weeks and 8 weeks ]

   This 8-item scale measures sleep problems against the DSM-5 criteria for insomnia disorder.

   Item responses are each scored 0-4, with scores from 0 to 2 indicating threshold criteria for insomnia disorder. Total score ranges 0-32, with a higher score indicating better sleep (cut-off for possible insomnia disorder is a total score from 0 to 2).

6. Generalised Anxiety Disorder 2-item scale (GAD-2) [ Time Frame: Baseline, 4 weeks and 8 weeks ]
   Items are rated for how often they have bothered the respondent over the last two weeks, from 0 ("not at all") to 3 ("nearly every day"). Total score is the sum of both items and ranges from 0 to 6 (cut-off for possible GAD is 3 or above).
7. Patient Health Questionnaire 2-item version (PHQ-2) [ Time Frame: Baseline, 4 weeks and 8 weeks ]

   This 2-item short-form self-report measure assesses symptoms of depression.

   Items are rated for how often they have bothered the respondent over the last two weeks, from 0 ("not at all") to 3 ("nearly every day"). Total score is the sum of both items and ranges from 0 to 6 (cut-off for possible major depressive disorder is 3 or above).

8. Psychological Outcome Profiles (PSYCHLOPS) [ Time Frame: Baseline, 4 weeks and 8 weeks ]

   This measure consists of 4 questions that are scored and designed to assess the impact of a person's intrusive memories.

   Questions 1b, 2b, 3b, and 4 are scored. These have a six-point ordinal scale ranging from 0 to 5 and are summed to generate a total score from 0 to 20. Higher values indicate the person is more severely affected.

9. World Health Organization Disability Assessment Schedule 12-item version (WHODAS 2.0) [ Time Frame: Baseline, 4 weeks and 8 weeks ]

   The 12-item, self-report version of the WHODAS 2.0 will be used to assess difficulties in relation to the impact of intrusive memories.

   Respondents rate how much difficulty they have had in each area in the past 30 days, from 0 (none) to 4 (extreme or cannot do). The overall score is calculated as a percentage of the maximum possible score (i.e., 48 points).

10. 5-level European Quality of Life 5 Dimension (EQ-5D-5L) [ Time Frame: Baseline, 4 weeks and 8 weeks ]

    The 5-level version of the EuroQol-5D (EQ-5D-5L) is a brief measure for assessing general quality of life and health status.

    Items assess mobility, self-care, usual activities, pain/discomfort and anxiety/depression each on a 5-point scale. 5 items are scored on a 5-point ordinal scale from 'no problem' (1) to 'highest level of problems' (5). Respondents also rate their overall health today from 0 (the worst health you can imagine) to 100 (the best health you can imagine). Scores are analysed separately (not summed).

11. Scale of Work Engagement and Burnout (SWEBO) [ Time Frame: Baseline, 4 weeks and 8 weeks ]

    This 18-item self-report measure assesses work engagement and burnout.

    The work engagement subscale consists of 9 items assessing three dimensions (vigour, attentiveness, dedication). Respondents rate how often they have felt each descriptive in the past two weeks, from 1 (not at all) to 4 (all the time). The mean score is calculated for two subscales: engagement and burnout (9 items each).

12. Sickness absence [ Time Frame: Baseline, 4 weeks and 8 weeks ]
    Single item assessing self-reported number of sick days taken from work in the last 4 weeks. Total scoring includes total number of sick days.
13. Intention to leave job [ Time Frame: Baseline, 4 weeks and 8 weeks ]
    This 3 items questionnaire is used to assess participants' intention to leave their job e.g. "I think a lot about leaving the job", each rated from 1 (strongly agree) to 5 (strongly disagree). The total score ranges 3 to 15, with a lower score indicating stronger intention to leave the job.
14. Weekly Work Pattern [ Time Frame: Baseline, 4 weeks and 8 weeks ]
    Two items asses the number of days worked and number of night shifts worked in the last week (both with responses from 0 to 7). Items are examine separately (not summed).

Other Outcome Measures:

1. Support from managers and from family/friends [ Time Frame: Baseline ]
   The 2 item questionnaire asks "During the COVID-19 pandemic, how well supported have you been by your supervisors/managers?" and "how well supported have you been by your family and friends?" The response is rated as "not at all", "quite a bit", "moderately", "quite a bit", or "extremely"
2. Changes to health and work [ Time Frame: 4 weeks and 8 weeks (both arms) ]
   The 6-item questionnaire questionnaire will be used to assess the occurrence of any new traumatic events, any additional stressful life events (e.g. relationship problems, financial problems), new treatments received, social support received, changes to the job, or changes to the number of hours worked per week since the last assessment.
3. Optimisation Assessment [ Time Frame: Baseline, 4 weeks and 8 weeks ]
   Rates of recruitment, intervention use/adherence, outcome measure completion and participant attrition will be assessed.
4. Feedback questionnaire [ Time Frame: Week 4 (immediate intervention arm), Week 8 (delayed intervention arm) ]
   The first ten items assess how easy, helpful, distressing, burdensome and acceptable participants found the intervention, how willing they would be to use it in the future, how confident they would be in recommending it to a friend and how much they feel it could be used to support staff within NHS ICUs, each rated from 0 (not at all) to 10 (very). The last two items ask how the intervention could be improved, for any other comments or suggestions about the intervention, and for the occurrence of any adverse events, all with an open response.
5. Optional qualitative interview [ Time Frame: Week 5 (immediate intervention arm), Week 9 (delayed intervention arm) ]
   Qualitative interview will consist of a number of questions designed to gain an in-depth understanding of participants' experience of using the intervention, including acceptability, improvement suggestions, training/psychoeducation materials, potential barriers/facilitators to recruitment and uptake, and support needed for remote intervention delivery.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria:

• Aged 18 or above.
• Able to read, write and speak in English.
• Worked in a clinical role in an NHS Intensive Care Unit or equivalent during the COVID-19 pandemic (e.g. as a member of ICU staff or deployed to work in the ICU during the pandemic)
• Experienced at least one traumatic event related to their work during the COVID-19 pandemic, meeting criterion A of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for Post-Traumatic Stress Disorder (PTSD): "exposure to actual or threatened death, serious injury, or sexual violence" by "directly experiencing the traumatic event(s)" or "witnessing, in person, the event(s) as it occurred to others"
• Experience intrusive memories of the traumatic event(s).
• Experienced at least three intrusive memories in the week prior to screening.
• Have internet access.
• Willing and able to provide informed consent and complete study procedures (including briefly listing their intrusive memories (without going into any detail), and playing the brief digital imagery-competing task with particular mental rotation instructions, and completing an online intrusive memory diary).
• Willing and able to be contacted by the research team during the study period.

Exclusion criteria:

• Have fewer than three intrusive memories during the run-in week.

We will not exclude those undergoing other treatment for PTSD or its symptoms, so the study is as inclusive as possible to meet the challenges ICU staff are facing during the COVID-19 pandemic.

Contacts and Locations

Locations

United Kingdom

P1vital Products Limited

Wallingford, Oxfordshire, United Kingdom, OX10 8BA

Sponsors and Collaborators

P1vital Products Limited

Wellcome Trust

Uppsala University

Intensive Care Society

University of Nottingham

Investigators

• Principal Investigator: Emily Holmes; Uppsala University

More Information

Additional Information:

Published paper of primary outcome results (Bayesian analysis) 

Published paper of primary outcome results (Frequentist analysis) 

Publications of Results:

Ramineni V, Millroth P, Iyadurai L, Jaki T, Kingslake J, Highfield J, Summers C, Bonsall MB, Holmes EA. Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention. Mol Psychiatry. 2023 Jul;28(7):2985-2994. doi: 10.1038/s41380-023-02062-7. Epub 2023 Apr 26.

Other Publications:

Iyadurai L, Highfield J, Kanstrup M, Markham A, Ramineni V, Guo B, Jaki T, Kingslake J, Goodwin GM, Summers C, Bonsall MB, Holmes EA. Reducing intrusive memories after trauma via an imagery-competing task intervention in COVID-19 intensive care staff: a randomised controlled trial. Transl Psychiatry. 2023 Sep 1;13(1):290. doi: 10.1038/s41398-023-02578-0.

• Responsible Party: P1vital Products Limited
• ClinicalTrials.gov Identifier: NCT04992390
• Other Study ID Numbers: P1V-GAINS-IN01
• First Posted: August 5, 2021
• Last Update Posted: September 8, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: An anonymised database of individual participant data, along with a data dictionary, as well as the Clinical Study Report (which will include summarised anonymised participant data), will be shared on the Open Science Framework.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: We aim to share the Study Protocol and Statistical Analysis Plan when the final participant allocated to delayed arm completed the guided intervention. The Clinical Study Report will be shared when available following publication. Supporting information mentioned above will be shared indefinitely and with no end date on Open Science Framework Platform.

Access Criteria

Anonymised research data will be made available on open science frame work (OSF) indefinitely.

OSF is an open source web application that is freely accessible to public and scientific community.

OSF links are:

Protocol, Optimisation SAP (Bayesian) and Descriptive SAP (Frequentist):

https://osf.io/2xn5m/

Bayesian paper analysis scripts, database and data code book:

https://osf.io/m5cvj/

Frequentist paper analysis scripts, database and data code book: https://osf.io/j9v2z/

• URL: https://osf.io/2xn5m/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No