Adaptation of Cognitive Enhancement Therapy for Persons at Clinical High Risk for Psychosis
Condition: Psychosis
MeSH terms: Psychotic Disorders; Mental Disorders
Study type: Interventional

Summary: 
      The purpose of this study is to test the feasibility of a modification of CET (Cognitive
      Enhancement Therapy) to address symptomatic and functional difficulties associated with
      Clinical High Risk for Psychosis (CHR).

      Cognition for Learning and for Understanding Everyday Social Situations (CLUES) is designed
      to improve cognitive functioning (e.g., memory, attention, planning, etc.) in order to
      improve school, work, and social functioning. CLUES includes the following:

        1. Computerized cognitive remediation ("exercises") to improve cognition.

        2. Social-cognitive skills group designed to teach participants to act wisely in social
           situations.

        3. Individual coaching sessions designed to enhance translation of skills learned from
           computer exercises and the group into real life.

      CLUES is based on Hogarty and Greenwald's Cognitive Enhancement Therapy (CET), which was
      designed for treating individuals with schizophrenia. Research on CET for individuals with
      schizophrenia has found that CET appears to have helped participants improve cognition and
      social and work functioning.

      This study will investigate the feasibility of CLUES for young people who are showing signs
      of clinical risk for psychosis.

      Part 1: Preliminary open label trial of CLUES (n=8) to examine preliminary evidence of target
      engagement (change in cognition and social cognition), to refine assessment and recruitment
      approaches, to further optimize the treatment manual, and to ascertain feasibility and
      tolerability.

      Part 2: Preliminary randomized controlled trial of CLUES vs supportive therapy (ST) +
      computer games to explore preliminary evidence of efficacy of CLUES vs. the control treatment
      (n=30).
    

Detailed description: 
      Psychotic disorders such as schizophrenia (SZ) are among the most disabling conditions in all
      of medicine. These disorders typically begin in adolescence or young adulthood, and are
      preceded by premorbid impairments in cognitive and social function dating from early
      childhood; these deficits worsen in adolescence and are accompanied by sub-threshold positive
      and negative symptoms (the prodromal, or clinical high risk state, CHR) before onset of the
      first psychotic episode. Recent staging models have operationalized approaches to defining
      early and late phases of CHR; Early CHR (stage 1a) is characterized by cognitive impairments
      and sub-threshold negative symptoms, while late CHR (stage 1b) is associated with
      sub-threshold positive and disorganized symptoms as well as further cognitive and functional
      declines. The emergence of cognitive and functional decline in Individuals at CHR who convert
      to psychosis highlights the importance of early intervention.

      Impairments in cognition are present in children who later go on to develop SZ. Impairments
      in cognition are key rate-limiting factors to functional recovery from psychotic disorders
      and include deficits in psychomotor speed, memory, attention, reasoning, and social
      cognition. The latter include deficits in perspective-taking, emotion perception and
      regulation, clearly linked to functional outcome in SZ. Perspective-taking (ability to
      understand the thoughts, feelings, and intentions of others) and emotion regulation (ability
      to have cognitive control over emotional stimuli) are critical for healthy social
      development; their impairment is a major contributor to social and functional disability.

      There is compelling evidence from recent meta-analyses that psychosocial approaches to
      cognitive remediation are effective in SZ. We have shown that a psychosocial cognitive
      rehabilitation known as Cognitive Enhancement Therapy (CET) substantially improves both
      social cognition and employment rates among patients with early course SZ. The effects were
      durable at 1 year following end of treatment.

      CET is a comprehensive, developmental approach to address social and non-social cognitive
      deficits in SZ; it seeks to facilitate the development of adult social-cognitive milestones
      (e.g., perspective-taking, social context appraisal) by shifting thinking from reliance on
      effortful, serial processing to a "gistful" and spontaneous abstraction of social themes
      (details about CET in section C.2.6). CET targets social-cognitive impairments in
      perspective-taking and emotion regulation through computerized training in basic
      neurocognitive processes, and the use of social-cognitive rehabilitation groups. The efficacy
      of CET for remediating social-cognitive impairments in perspective-taking and emotion
      regulation in SZ presumably reflects an underlying change in fronto-temporal brain function
      and connectivity during the course of treatment, made possible by the plasticity of the human
      brain. CET may also protect against gray matter loss, and even support fronto-temporal gray
      matter growth in service of social-cognitive enhancement in SZ.

      In this study, we plan to modify CET for individuals at CHR. We will develop a manual for
      CLUES and systematically test the acceptability, tolerability, adherence and preliminary
      proof of target engagement (part 1), and preliminary efficacy in a proof of concept open
      label trial (part 2). An important recent initiative in treatment development is to ensure
      informed, data-driven decisions early in clinical trials, i.e. to identify therapeutic
      targets, obtain evidence of target engagement and a proof of concept of efficacy prior to
      proceeding to expensive clinical trials. To pursue this goal, we will evaluate CET effects on
      cognition and social cognition in part 1 before efficacy testing in part 2.

      Overview:

      This study will be organized in two parts:

      Part 1: Preliminary open-label CLUES group (n=8) to verify target engagement (using cognition
      and social cognition measures), to evaluate feasibility and tolerability, and to iteratively
      refine the manual.

      Part 2: Small, randomized trial comparing CLUES (2 groups, n=15 each to a control condition
      (psychotherapy + an active computer-based program, Sporcle, with simple/ non-demanding
      computer games).CLUES Interventions in this part will be optimized based on part 1 results.

      Interventions:

      1) Individualized assessment: The intervention begins with a comprehensive assessment of
      neurocognition and social cognition, as well as cognitive style. This informs development of
      an individualized coaching plan targeting the individual's areas of difficulty. The
      individualized coaching plan sets CET apart from other more standardized cognitive
      remediation approaches. 2) Neurocognitive remediation sessions. Weekly CET cognitive
      remediation sessions involve working with a partner (peer) and is facilitated by a clinician.
      This provides a unique opportunity for participants to complete "bottom up" cognitive
      exercises designed to improve processing speed, attention, memory and problem solving while
      also learning to negotiate the social tasks involved in working with a partner (e.g., making
      appropriate small talk, paying attention and keeping score while a partner engages in the
      tasks, providing encouragement when a partner struggles, and/or managing feelings that come
      up when the participant struggles more than their partner). 3) Social cognitive group:
      Participants take part in weekly social cognitive groups concurrently with neurocognitive
      training and individual sessions. This group is designed to help participants learn
      strategies for applying skills to improve non-social and social cognition and provide in vivo
      learning experiences to foster the development of social wisdom and interpersonal success. A
      broad, theoretically-driven array of social-cognitive abilities are targeted in the social
      cognitive groups, which range from abstracting the "gist" or main point in social
      interactions to perspective taking, social context appraisal, and emotion management.
      Participants actively engage in the social cognitive groups by responding to unrehearsed
      social exchanges, presenting homework, participating in cognitive exercises that focus on
      experiential learning, providing feedback to peers, and chairing homework sessions. 4)
      Individual coaching: Weekly individual coaching sessions provide opportunities for the
      intervention to be further tailored to the participants' specific goals, cognitive
      difficulties and cognitive style. Coaching sessions help the participant to develop a
      training plan, digest information and skills learned in social cognitive group and in the
      neurocognitive training sessions, and figure out how to apply them to make progress toward
      personal goals.

      Control treatment (Part 2 only):

      During part 1, all participants will take part in CLUES. During part 2, we will conduct a
      small randomized trial in which participants will be randomized to CLUES or the control
      intervention (n=15 each). The control intervention will consist of weekly supportive personal
      therapy plus 2 hours/ week of participation in Sporcle, a web-based, publicly available
      active computer-based, generic, quiz-type program. Sporcle provides quizzes on subject areas
      from geography to basic arithmetic to pop-culture. Sporcle includes games such as identifying
      popular logos, naming as many pictured fruits and vegetables as possible, and listing state
      capitols. Based on online user data and on level of difficulty, relatively easy exercises are
      chosen (averaging approximately 70% accuracy (i.e. 70% of quiz items correctly answered, on
      average). Games are presented to participants on "prescription cards" each week, with an aim
      of participating in 2 hours per week (equivalent to 1 hour of lumosity plus 1 hour per week
      paired computer training.

      In ST, patients meet individually with a therapist to learn and practice a variety of
      stress-reduction and illness management techniques. The ST approach is designed to be
      sensitive to the patient's stage of development and divided into 2 phases. The first, basic
      phase (0-3 months) focuses on psychoeducation about risk for psychosis (to be developed
      during phase 1), the role of stress in the disorder, and symptom exacerbation, and introduces
      basic coping strategies to minimize and/or avoid stress in one's life.The second, phase (4-6
      months) advances to a personalized approach to the identification of early cues of distress
      and the application of healthy coping strategies to enhance adjustment. By tailoring the
      treatment to the patient's stage of recovery, Patients meet weekly with a therapist, although
      more frequent sessions are available if needed. We will seek to match the number of sessions
      or hours of treatment between CLUES and ST.

      Participants will be assessed at: 1) Baseline, 2) 3 months into the program, 3) at the time
      of completion of the program (6 months), and 4) 3 months following completion of CLUES, in
      the part 2 trial only (Table 1). All these assessments will be administered during part 1 to
      assess acceptability, applicability to the CHR population and assessment burden; Observations
      will then be used to optimize assessment battery for part 2.
    

Intervention name(s): CLUES; therapy and computer games
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Cognition for learning and for understanding everyday social situations intervention described above; Weekly psychotherapy+ computer games such as sporcle
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: clinical high risk for psychosis; psychosis prodrome; cognitive remediation; psychosis prevention