Efficacy of ISST in Schizophrenia

Study Overview
=================
Brief Summary
-----------------
The ISST study investigates whether integrated social cognitive remediation and social behavioral skills therapy is more efficacious in improving functional outcome and treatment adherence than an active control treatment comprising drill-and-practice oriented neurocognitive remediation.

Detailed Description
-----------------
Deficits in social functioning are a defining, very burdening feature of schizophrenia precluding patients from participating in a satisfying life. Traditional drug and psychosocial therapy and available specific treatment strategies that directly target single key determinants of functional outcome like neurocognition, social cognition, and social behavioral skills have produced only moderate effects leaving an urgent need for further optimization. The present trial aims to more efficaciously improve functional outcome by integrating social behavioral and social cognitive treatment strategies. Six months of Integrated Social Cognitive and Behavioral Skills Therapy (ISST) will be compared with Neurocognitive Remediation Therapy (NCRT) as active control condition in a randomized multicenter clinical trial using a two group pre-post design with 2x90 patients in the remitted early phase of schizophrenia. Beyond all-cause-discontinuation as common primary outcome of all clinical trials of the ESPRIT-consortium, measures of functional outcome and subjective quality of life, patient experience as well as neurocognitive, social-cognitive and social behavioral measures will be assessed at baseline (V0), after completion of treatment (V6), and after 6 months follow-up (V12). ISST is expected to reduce the one-year discontinuation rate by 20% compared with NCRT, and to be superior in functional outcome measures by an effect size of at least d=0.42.

Official Title
-----------------
Efficacy of Integrated Social Cognitive and Behavioral Skills Therapy (ISST) in Improving Functional Outcome in Schizophrenia

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Behavioral: Integrated Social Cognitive and Behavioral Skills Therapy
* Behavioral: Neurocognitive Remediation Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent DSM-IV-TR diagnosis of schizophrenia (295.10-30, 295.90) PANSS at baseline: total score ≤ 75 Proficiency in German language. Exclusion Criteria: Lack of accountability Positive urine drug-screening for illicit drugs at screening (except cannabinoids and benzodiazepines) Serious suicidal risk at screening visit Other relevant axis 1-diagnoses according to diagnostic interview (MINI); Other relevant neurological or somatic disorders Verbal IQ<80 (MWT-B)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Integrated Social Cognitive and Behavioral Skills Therapy<br>The Integrated Social Cognitive and Behavioral Skills Therapy (ISST) shall target expressive and interactional behavior skills together with those social cognitive domains (facial and prosodic affect recognition, social perception, theory-of-mind) known to be most impaired (Savla, 2012) and most closely associated with functional outcome (Fett, 2012) in schizophrenia. | Behavioral: Integrated Social Cognitive and Behavioral Skills Therapy<br>* The Integrated Social Cognitive and Behavioral Skills Therapy (ISST) is a newly developed treatment program. It is based on the Training of Affect Recognition (Wölwer et al. 2005) and common social skills trainings, which are combined in an integrated rather than a sequenced manner. ISST uses both repeated practice and strategy-based training, and consists of 12 individual sessions, 5 group sessions and 1 individual final session over a period of 6 months.<br>* Other names: ISST;|
| Active Comparator: Neurocognitive Remediation Therapy<br>The Neurocognitive Remediation Therapy (NCRT) shall target impairments in attention, memory, and executive functions as an active comparator to the ISST. | Behavioral: Neurocognitive Remediation Therapy<br>* The Neurocognitive Remediation Program (NCRT) is based on a neurocognitive training already used as active control condition in our earlier studies (Wölwer et al. 2005, Klingberg et al. 2011). The present version of NCRT is matched in dose, mode and scheme of application to the ISST, but differs from the ISST regarding targeted cognitive domains and preferred training strategy (predominantly drill and practice based). The NCRT provides the same amount of group interaction and companionship as well as the same amount of guided community activity as in the ISST, but is structured in such a way that interactional behavior is secondary (e.g. by competition-like tasks rather than cooperative tasks). Thus therapeutic attention and commitment are held constant across study conditions.<br>* Other names: NCRT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Cause Discontinuation | All Cause Discontinuation is defined as 1) not keeping appointments to treatment or diagnostic sessions as scheduled for more than 6 weeks and/or (2) not being traceable despite extensive efforts by the intervention team to reengage the patient throughout the entire intended treatment period and/or (3) withdrawal of consent by the patient (4) rater induced discontinuation of the study treatment (eg. for safety criteria) (5) not taking psychotropic drugs as prescribed for more than 14 consecutive days and/or (6) relevant worsening of symptoms. | 6 months, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Adherence 1 | SES (Service Engagement Scale, Tait, Birchwood & Trower 2002) | 6 months, 12 months | 
| Treatment Adherence 2 | DAI-10 (Drug Attitude Scale, Goodstadt et al. 1978) | 6 months, 12 months | 
| Treatment Adherence 3 | PATHEV (Psychotherapy Attitude Scale, Schulte 2005) | 6 months, 12 months | 
| Psychosocial Functioning 1 | FROGS (Functional Remission of General Schizophrenia, Lorca et al. 2009) | 6 months, 12 months | 
| Psychosocial Functioning 2 | UPSA-Brief (University of California Performance Based Skills Assessment, Mausbach et al. 2007) | 6 months, 12 months | 
| WHOQUOL-Bref (Quality of Life) | WHOQUOL-BREF (World Health Organization Quality of Life, WHO 1996) | 6 months, 12 months | 
| Neurocognitive Performance (verbal memory) | VLMT (verbal learning and memory test, Helmstaedter, Lendt & Lux 2001 | 6 months, 12 months | 
| Neurocognitive Performance (working memory) | DSF, DSB (digit sequencing forward/backward, Wechsler 1981) | 6 months, 12 months | 
| Neurocognitive Performance (processing speed 1) | DSST (digit symbol substitution test, Wechsler 1981) | 6 months, 12 months | 
| Neurocognitive Performance (processing speed 2) | TMT-A, -B (Trail-Making-Test, Reitan 1956) | 6 months, 12 months | 
| Socialcognitive Performance (affect recognition) | PFA (Picture of Facial Affect Test, Ekman & Friesen 1976) | 6 months, 12 months | 
| Socialcognitive Performance (theory of mind) | MASC (Movie for the Assessment of Social Cognition, Dziobek et al. 2006) | 6 months, 12 months | 
| Psychopathology/Symptoms 1 | PANSS (Positive and Negative Syndrome Scale, Kay, Fiszbein & Opler 1987) | 6 months, 12 months | 
| Psychopathology/Symptoms 2 | CDSS (Calgary Depression Rating Scale for Schizophrenia, Addington, Addington & Maticka-Tyndale 1993) | 6 months, 12 months | 
| Psychopathology/Symptoms 3 | BSI (Brief Symptom Inventory, Derogatis & Melisaratos 1983) | 6 months, 12 months | 
| Suicidality | Incidence of suicide/suicide attempt or severe suicidal crisis (CDSS Item 8 ≥ 2) | Assessed every 4-6 weeks from date of randomization until 1 year or until discontinuation (whatever came first) | 
| Severe symptom worsening | CGI (Clinical Global Impression Scale Item 2 ≥ 6) | Assessed every 4-6 weeks from date of randomization until 1 year or until discontinuation (whatever came first) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
social cognition, social skills, cognitive remediation, functional outcome, treatment adherence