Efficacy of ISST in Schizophrenia

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Behavioral: Integrated Social Cognitive and Behavioral Skills Therapy; Behavioral: Neurocognitive Remediation Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Alzey, Germany
    • Rheinhessen-Fachklinik Alzey
  • Berlin, Germany
    • Vivantes Klinikum Am Urban
  • Bonn, Germany
    • Dept. of Psychiatry and Psychotherapy, University of Bonn
  • Cologne, Germany
    • Dept. of Psychiatry and Psychotherapy, University of Cologne
  • Duesseldorf, Germany
    • Dept. of Psychiatry and Psychotherapy, University of Düsseldorf
  • Tübingen, Germany
    • Dept. of Psychiatry and Psychotherapy, University of Tübingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Integrated Social Cognitive and Behavioral Skills Therapy; 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; 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.; Other Names: ISST
Active Comparator: Neurocognitive Remediation Therapy; 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; 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.; 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)

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Collaborators: University of Cologne; University Hospital, Bonn; University Hospital Tuebingen; University Hospital of Cologne; Rheinhessen-Fachklinik Alzey; Zentralinstitut für Seelische Gesundheit Mannheim; Vivantes Klinikum am Urban
• Investigators: Principal Investigator: Wolfgang Wölwer, Prof. Dr., Dept. of Psychiatry and Psychotherapy, University of Düsseldorf

Publications and helpful links

General Publications

• Wolwer W, Frommann N, Lowe A, Kamp D, Weide K, Bechdolf A, Brockhaus-Dumke A, Hurlemann R, Muthesius A, Klingberg S, Hellmich M, Schmied S, Meyer-Lindenberg A; ISST study group. Efficacy of Integrated Social Cognitive Remediation vs. Neurocognitive Remediation in Improving Functional Outcome in Schizophrenia: Concept and Design of a Multicenter, Single-Blind RCT (The ISST Study). Front Psychiatry. 2022 Jun 21;13:909370. doi: 10.3389/fpsyt.2022.909370. eCollection 2022.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: February 3, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 10, 2016

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: social skills; social cognition; cognitive remediation; functional outcome; treatment adherence
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: ISST2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data shall be shared within the German research network ESPRIT (Enhancing Schizophrenia Prevention and Recovery through Innovative Treatments) as well as with other German research networks funded by the BMBF (call "Psychische Erkrankungen").