Objectives {7}

The objective of this study is to evaluate the efficacy of GAIN Lite added to EUC for adults with mild-to-moderate PPCS compared to EUC only. It is hypothesised that GAIN Lite added to EUC is superior to EUC only. The primary outcomes are self-reported PPCS and self-reported limitations in daily life from baseline to 24 weeks after baseline.

Eligibility criteria {10}

At enrolment, a clinical assessment of all participants is performed by physicians at HNC to verify the diagnosis and to ensure eligibility criteria are met. The clinical assessment consists of a neurological examination and a short, standardised medical history interview. Non-eligible participants are recommended to contact their GP for further advice if needed. Participants are recruited based on the following inclusion criteria: (1) Concussion caused by a head trauma according to the diagnostic criteria recommended by the Danish Consensus Report on Commotio Cerebri [29]. The criteria are based on recommendations by the World Health Organization (WHO) Task Force [2], but with the amendment that there must have been direct contact between the head and an object to rule out acceleration–deceleration traumas; (2) Age 18 to 60 years at the time of the trauma; (3) Mild-to-moderate PPCS defined by a total score of 10–30 on the Rivermead Post-Concussion Symptom Questionnaire (RPQ) [30] within 1 week before enrolment in the study. As there is no universal sub-division of PPCS, the definition emerged after several discussions in the research group. The definition is roughly consistent with the mild-to-moderate categories by Potter et al. [31]; (4) Able to understand, speak and read Danish; (5) Living in Central Denmark Region and (6) Identified from registers of the emergency departments or referred by GPs within 2–4 months after a concussion. Exclusion criteria are (1) Objective neurological findings; (2) Previous concussion within the last 2 years with PPCS at the time of the present concussion; (3) Severe misuse of alcohol, prescription drugs and/or illegal drugs and (4) Severe psychiatric co-morbidity (e.g. bipolar disorder, autism, psychotic disorder (lifetime)) or severe neurological disease (e.g. multiple sclerosis) that impedes participation in the programme.

Who will take informed consent {26a}

Prior to the clinical assessment and inclusion in GAIN Lite, written informed consent will be obtained from each participant. Informed consent is based on written information about GAIN Lite, which is emailed to potential participants prior to the clinical assessment. Furthermore, a physician will provide verbal information on the project through a video or telephone consultation 1–4 weeks before the clinical assessment. In case of no prior consultation, verbal information will be provided by the designated physician just before the clinical assessment. The physicians have no role in delivering EUC or GAIN Lite.

Additional consent provisions for collection and use of participant data and biological specimens {26b}

No biological specimens will be collected during the present study.

Explanation for the choice of comparators {6b}

Evidence-based recommendations for effective non-pharmacological treatment for people with PPCS are sparse [15]. However, early written or oral information, reassurance and advice are recommended [15, 32]. Hence, providing EUC as standard treatment to all participants is considered most ethically sound for current participants, although potentially limiting the possibility to demonstrate a potential treatment effect of GAIN Lite for future people with mild to moderate PPCS.

Intervention description {11a}

Enhanced usual care—EUC

Immediately after the clinical assessment, all participants are shortly introduced to a biopsychosocial understanding of PPCS [33], advised to gradually resume premorbid activities and are introduced to balance activity and rest [34, 35]. Furthermore, reassurance that a good prognosis is expected is given. The short introduction and advice are considered to be EUC and is performed by a health professional with knowledge about concussion, the development of PPCS and the principles of GAIN Lite. EUC has a duration of maximum 30 min. For a summary of EUC see Fig. ​Fig.11.

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Fig. 1

Summary of content, EUC

GAIN Lite

The add-on GAIN Lite intervention is a remote programme based on the treatment principles and content from GAIN with a duration of 8 weeks [24]. The intervention is overall intended to reduce PPCS and decrease limitations in daily life by modifying symptom-perpetuating illness cognition and behaviours. The intervention contains an initial remote interview, self-administrated e-learning videos and voluntary remote counselling with an allocated occupational- or physiotherapist. The timeline of GAIN Lite is illustrated in Fig. ​Fig.22.

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Fig. 2

Timeline of GAIN Lite

Within a week after randomisation, the allocated therapist makes a short phone call to arrange the programme start. Typically, the first session (by phone) takes place within 2 weeks after the short phone call and aims to facilitate therapeutic alliance and introduce the e-learning videos. The e-learning videos take the participants through a 6-stage programme. Each video has a duration of 5–10 min including reflective questions. The link to the videos is emailed immediately after the first session and can be accessed by the participants at any time throughout the 8-week intervention period. The second session (by phone or videoconference) takes place about a week after the link has been emailed and aims to link the participant’s reflections from the videos to the participant’s daily life, including illumination of individually important goal(s). The voluntary subsequent follow-up sessions (by phone or videoconference) are targeted to change symptom perpetuating illness cognition and behaviour in relation to the individual’s context and goal(s). The number and content of the individual sessions are based on shared decision-making, but it is recommended that each session has a maximum duration of 45 min. Furthermore, the upper limit of the individual sessions is 3 h during the 8-week intervention period. For a summary of the content in GAIN Lite see Fig. ​Fig.33.

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Fig. 3

Summary of content, GAIN Lite

Therapists experienced in health promotion, health education and/or in the facilitation of health behaviour change will facilitate the individual sessions. Furthermore, the therapists will be trained in basic principles of a cognitive behavioural approach according to the treatment manual of GAIN Lite [36–40].

To ensure fidelity and adherence to the intervention principles, a treatment manual has been developed. Furthermore, the therapists will receive 1 h of monthly supervision by a neuropsychologist who is an expert on PPCS and trained in supervision. Therapist meetings to share experiences and discuss practical issues are also planned monthly. Furthermore, the therapists are encouraged to reflect on their feedback and guidance after each session using a worksheet designed specifically for the present study. The treatment manual and the e-learning videos are available upon reasonable request to the corresponding author.

Criteria for discontinuing or modifying allocated interventions {11b}

There will be no specific criteria for discontinuing or modifying allocated interventions. However, participants will be informed that they have the right to withdraw their consent and reject further participation in GAIN Lite at any time without any consequences.

Strategies to improve adherence to interventions {11c}

At the first session, participants are encouraged to watch the videos before the second session. Adherence to the videos is logged, and the therapists can see if the participants played the videos. Moreover, the allocated therapist will send reminders by SMS or email to participants 1–2 days before each session. SMS is the preferred method. However, reminders are sent by email in advance of videoconferences since a conference link is included.

Relevant concomitant care permitted or prohibited during the trial {11d}

Participants are free to continue or seek other additional treatment during the period. A questionnaire on other treatments is emailed to participants at 24- and 36-week follow-up.

Provisions for post-trial care {30}

Based on feasibility tests of GAIN Lite and the original GAIN study, there is no anticipated harm. No compensation is provided for trial participation.

Outcomes {12}

The primary outcomes are mean changes in PPCS and limitations in daily life from baseline to 24 weeks after baseline (time frame: 6 months). Secondary outcomes are mean changes in illness cognition and illness behaviour from baseline to 12 weeks after baseline (time frame: 3 months) and in sickness absence and work ability from baseline to 36 weeks after baseline (time frame: 9 months). PPCS, limitation in daily life, illness cognition and illness behaviour are measured at four time points: at baseline, 12 (end of intervention), 24 and 36 weeks after baseline. Additionally, sickness absence and work ability will be measured at baseline and 36 weeks after baseline. Furthermore, register-based data will provide additional measures during the first year after baseline.

The register-based data include monthly proportion of participants on sick leave (defined as public assistance benefits related to illness), monthly proportion of employed participants (defined as receiving no public assistance benefits except from state education fund grants monthly) and monthly degree of job stability (based on whether labour market contributions have been paid). All outcome measures and data collection time points are shown in Table ​Table11.

Participant timeline {13}

Potential participants will be identified through the hospital’s Business Intelligence (BI) portal of the Central Denmark Region or referred by GPs within 2–4 months post-concussion. Baseline questionnaires will be answered within 1 week before the clinical assessment. The clinical assessment is performed as soon as possible after informed consent and no later than 7 months after the trauma. Immediately after the clinical assessment, participants receive EUC. Allocation is emailed to participants a week after the clinical assessment. The participant timeline is illustrated in Fig. ​Fig.44.

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Fig. 4

Participation timeline

Sample size {14}

In the present study, RPQ and the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P) are used to measure the primary outcomes. The sample size calculation is based on two studies: the original GAIN study [24] and a study by van der Zee et al. [41]. To account for having to primary outcomes, we set a 2.5% threshold for significance level to adjust for multiple testing (Bonferroni’s correction) [42]. In the original GAIN study, the control group had a mean of 37.4 (SD 7.4) on the RPQ total score at baseline. Furthermore, a mean difference of 7.6 points between treatment groups (EUC and EUC+GAIN) was found on the RPQ total score 3 months after end of treatment. Since the spectrum of symptoms in this present study is lower compared to the original GAIN study, the best guess is that we will be able to detect a difference of 4 points in RPQ total score 24 weeks after baseline. For the same reason, the sample size estimated in the present study is based on the SD from the control group at baseline in the original GAIN study. To detect a mean difference in RPQ total score of 4 points (SD=7) at 24-week follow-up with a two-sided significance level of 2.5% and power of 80% with equal allocation to two arms would require 60 participants in each arm. To allow for 10% dropout, 66 will be recruited per arm, i.e. 132 in total. The scientific literature on which the sample size calculation of USER-P could be based on is sparse. However, in the study by van der Zee et al. [41], a mean difference of 5.4 (SD 17.2) was found on the restriction scale from baseline to 4-month follow-up in a population with neurological diseases receiving a rehabilitation programme. Based on the study by van der Zee et al., but taking into consideration that the sample included in this present study is less impaired and without degenerative diseases, it is assumed that it is possible to detect a difference in USER-P total score of 10 points. To detect a mean difference in USER-P total score of 10 points (SD=17) at 24-week follow-up with a two-sided significance level of 2.5% and power of 80% with equal allocation to two arms would require 57 participants in each arm. To allow for 10% dropout, 63 will be recruited per arm, i.e. 126 in total. In sum, 66 participants in each arm are recruited to ensure both sample size calculations are met.

Concealment mechanism {16b}

To conceal allocation, the randomisation table uploaded in REDCap is only accessible to the REDCap administrator throughout the study. Allocation concealment will be ensured, as randomisation will not take place until the participant has been included in the study after all baseline measurements, the clinical assessment and EUC have been completed.

Plans to promote participant retention and complete follow-up {18b}

Responses to the self-reported follow-up questionnaires will be observed closely by the project data manager and the PI. If no or incomplete response to the questionnaires, participants will be contacted twice by email.

Data management {19}

Study data are collected and managed using REDCap, which is a secure web-based software platform designed to support data capture for research studies hosted by Aarhus University [52]. REDCap provides (1) an intuitive interface for validated data capture; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages and (4) procedures for data integration and interoperability with external sources. The validation features (e.g. range checks for data values) in REDCap will be used in all questionnaire set-ups. The project data manager administers REDCap access within the REDCap system during the whole project.

Confidentiality {27}

The present study will be carried out in accordance with the rules of the Helsinki Declaration II and adhere to the Danish Data Protection Agency. All data collection and management are in compliance with the General Data Protection Regulation guidelines. Handling of data will be conducted according to general guidelines for encryption and anonymisation. Data to be analysed locally will be extracted from REDCap and immediately uploaded to MidtX which is a secure digital collaboration platform designed by Central Denmark Region to ensure secure storage of data from research and quality projects. Data to be merged with register-based data will be extracted from REDCap and immediately uploaded to the research computers at Statistics Denmark using the Statistics Denmark encrypted upload function.

Interim analysis {21b}

Not applicable. Interim analysis will not be performed in the present study.

Methods for additional analysis (e.g. subgroup analysis) {20b}

Within the MMRM, the treatment effect measured by RPQ, USER-P, B-IPQ and BRIQ will be subdivided by age, sex and baseline assessment. Additionally, mediation analysis is planned to examine whether change in illness cognition and illness behaviour mediate change in PPCS and limitations in daily living.

Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}

Data will be analysed according to the intention-to treat principles. Data will be analysed using linear mixed models for repeated measures providing unbiased estimates when data are missing at random or missing completely at random [56]. Furthermore, per-protocol analysis for completers defined as participants who received the first and second session and watched the e-learning videos will be performed.

Composition of the data monitoring committee, its role and reporting structure {21a}

Data monitoring committee will not be included in the present study as sponsors are not involved in the study design, data collection or analysis. Furthermore, data are collected using public administered systems (REDCap and Statistics Denmark). The research group will be in charge of reporting immediately to the PI about any adverse incidence.

Adverse event reporting and harms {22}

No adverse effect of the intervention is expected, as neither previous results from the original or the up-scaled GAIN studies nor the finding from the development of GAIN Lite showed any adverse effects. A transient and harmless increase of some symptoms can be expected in some cases because of the gradual return to activity. However, the intervention will be adjusted to individual tolerance. Nevertheless, any related or unrelated adverse events will be reported to the Ethics Committee in the Central Denmark Region once yearly.

Frequency and plans for auditing trial conduct {23}

The Ethics Committee in the Central Denmark Region is free to make an audit at any time during the trial. Access to the source data and study-related files is granted on such occasions. All documents and data analyses will be available for auditing for at least 5 years after the end of the study.

A gratefully acknowledge to the research staff who support this project.