The Effect of Hypnotic Suggestion After Acquired Brain Injury or Concussion
Condition: Acquired Brain Injury; Concussion, Brain
MeSH terms: Brain Injuries; Brain Concussion; Wounds and Injuries
Study type: Interventional

Summary: 
      A recent randomized clinical trial (RCT) demonstrated large effects of hypnotic suggestion on
      working memory following acquired brain injury. However, no studies have investigated
      long-term effects (> 2 months) effects on return to work (RTW).

      Therefore the aim is in a RCT to study the effect of hypnotic suggestion on RTW in employed
      individuals with acquired brain injury or concussion, that were referred to an out-patient
      municipal vocational rehabilitation center in Denmark.

      Participants were randomized to a passive (treatment as usual), active comparison (a weekly
      treatment session of mindfullness-based stress reduction for four weeks) or intervention
      group (a weekly treatment session of targeted suggestion for four weeks).

      Intention-to-treat analysis of the hypnosis effect on return to work within six months
      follow-up will be performed.

      Results Participants (N=77) have accepted and participated in the study. Effect measures are
      to be analysed.
    

Detailed description: 
      Introduction Hypnotic suggestion may be an effective treatment modality for cognitive
      sequelae following acquired brain injury and concussion. A recent RCT demonstrated large
      effects of hypnotic suggestion on working memory following acquired brain injury. Analyses of
      interview-data from that RCT also indicated large effects on sleep and Patient-Reported
      Outcomes (PROs). Previous studies have similarly shown clinically notable effects in the
      cognitive domain, although these have some methodological shortcomings. While stroke and
      concussion patients exhibit non-impaired responsiveness to hypnotic suggestion, there is
      little literature on the effect of hypnotic suggestion on concussion patients. In a
      non-controlled study, it was found that vertigo was completely removed following 1-10
      sessions of hypnosis in 63 out of 108 concussed patients and that vertigo was reduced in
      further 17 patients leaving only 28 (one in four) with no effect. In another smaller
      non-controlled study on patients with Mild Traumatic Brain Injury (MTBI), large effects on
      fatigue, anxiety, and depression were found. While the investigators have speculated about
      the mechanisms underlying the effect, the current goal of this research program is to provide
      the empirical basis for a verdict on whether hypnotic suggestion can be recommended for
      clinical practice. This is a pressing issue since brain injuries (stroke and TBI) constitute
      the world's second-most expensive health-related disability.

      Long-term effects on everyday outcome measures is of utmost importance in clinical settings.
      However, no studies have investigated long-term (> 2 months) effects on Return to Work,
      participation in society, or fatigue, and only one high-quality RCT has been conducted. Here,
      the investigators present the protocol for an RCT that aims to fill in these gaps. The
      present protocol is an effectiveness study in a vocational-rehabilitation setting, but in
      other respects, it closely replicates the efficacy study by the primary investigator.

      Objectives Estimate the effect of hypnotic suggestion on short- and long-term effects on
      Return to Work, participation in society, fatigue, and cognition. Given the promising
      findings in previous studies, the investigators hypothesize that hypnotic suggestion has
      positive effects in each of these domains.

      Methods (setting) All patient activities take place at an out-patient municipal vocational
      rehabilitation center in Denmark, including recruitment, testing, and treatment. The center
      specifically offers support to increase labor market attachment.

      Methods (recruitment) Potential participants were recruited from two departments in the
      vocational rehabilitation center: (1) a department specializing in citizens with
      brain-injury, concussion, whiplash, and related conditions. (2) A more general department
      which serviced a high rate of participants who had suffered a concussion. In both
      departments, the staff handed out participant information materials to all citizens who met
      inclusion 1-3 (age, etiology, and vocational history). The participants could optionally
      consent to giving their contact details to the project, contact the project by themselves, or
      decline. The first point of contact with the project was an oral information. The participant
      was given three days to consider consenting, though all participants made the decision
      immediately. After an initial screening by a project assistant, a list of eligible
      participants was sent to a dedicated non-blinded "coordinator" who randomly assigned
      participants to the groups while monitoring the balance between groups.

      Methods (Sequence generation)

      The coordinator used a computerized random sequence generator to assign participants to the
      three intervention groups. A practical constraint (unknown by the testers) was that a
      hypnotist should have exactly 5 participants in a day, if any. The procedure for
      randomization was:

      When there were 5+ screened participants, assign random numbers to the participants and
      allocate the participants with the lowest 5 numbers to a "general intervention group" and the
      rest to the passive control group. Then assign new random numbers to the
      intervention-allocated participants and assign the participants with the lowest N numbers to
      SBCR and the others to mindfulness. N is the number that would make the two intervention
      groups equal in size in the full dataset.

      If the number of passive controls exceeded the intervention groups, allocate 10 participants
      to the "general intervention group" and proceed cf. above. If the number of passive controls
      lacked the number in each intervention group, assign all participants to the passive control
      condition.

      Methods (Implementation and blinding) A dedicated project assistant (the "coordinator")
      allocated participants, informed them of their allocation, and booked a hypnotist. The
      participants only knew that there was a "hypnosis" and a "control" group but were blind to
      the fact that there were, in fact, two hypnosis groups. Participants were encouraged to only
      disclose their allocation with close peers that were not at the vocational center. The
      testers, center staff, principal investigator, data analysts, and other professionals were
      unaware of the allocation throughout the study.

      The allocation was saved at a secure server which only the coordinator had access to. The
      blinding was lifted when the last participant had had the 6-month follow-up test.

      The coordinator and hypnotists were unaware of the testing results. Participants were given a
      brief overview of their testing results upon completion of the 6-months follow-up.

      Blinding could be lifted for a single participant in case of serious side effects. If the
      side effect was serious enough to warrant halting the study, all blinding would be lifted to
      identify at-risk participants. The participants reported no serious side effects, so this
      procedure was never exercised.

      Methods (Data management) All questionnaire data were entered electronically to ensure data
      quality and completeness. Computerized tests were saved in csv files by the program.
      In-person administered tests were recorded in dedicated scoring sheets and then entered
      digitally. The testers saved all screening- and outcome data to a secure server, which only
      the testers had access to.

      Methods (Analysis) Intention-to-treat analysis of the hypnosis effect on return to work
      within six months' follow-up will be performed. The statistical software package Stata will
      be used.

      Ethics The study was approved by the regional ethics committee (The North Denmark Region),
      journal number N-20170022. Any participant-facing changes to the study were approved there.
      Participants always completed on the protocol they started.

      The consent was collected by the tester role in the "screening" section of the participant
      flow. The participant received written participant information in advance and an in-person
      oral information which briefly repeated the written materials and opened for discussion.
      Participants were given three days to consider whether to consent, though all participants
      decided immediately. The written consent was stored in a locker to which only testers had
      access.

      Declaration of interest The authors declare no financial interest in the study.
    

Intervention name(s): Hypnosis; Mindfulness-based stress reduction
Intervention type(s): Behavioral; Behavioral
Intervention description(s): A number of steps are taken to make the treatment arms identical in all other respects. The participants are unaware that there are two treatment arms to homogenize expectations. Each session is a manualized hypnosis script which is dictated by the hypnotist, including the hypnosis test. The only degrees of freedom for the hypnotist is in intonation and speed. Identical induction and termination is used in both arms and the scripts are of comparable durations.; A number of steps are taken to make the treatment arms identical in all other respects. The participants are unaware that there are two treatment arms to homogenize expectations. Each session is a manualized hypnosis script which is dictated by the hypnotist, including the hypnosis test. The only degrees of freedom for the hypnotist is in intonation and speed. Identical induction and termination is used in both arms and the scripts are of comparable durations.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Brain Injuries; Brain Concussion; Hypnosis; Return To Work; Sick Leave; Randomized Controlled Trial [Publication Type]