"Multimodal Prevention of Psychosis - Investigating Efficacy of N-Acetylcysteine and Psychotherapy in CHR-Patients"

NCT03149107 | Terminated Phase 3 DMC

• 1 other identifier: University Hospital, Bonn
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 10

Brief Summary

Schizophrenia is a severe mental disorder associated with significant impairments in affective, cognitive and social functioning. Consequently, a special interest in the prevention of schizophrenia and psychotic disorders has emerged. Pharmacological as well as psychological interventions show promising preventive effects. The purpose of this multicentric study is the investigation of possible preventive effects of a treatment combination containing a psychotherapy form and medication (N-Acetylcytein - NAC) in individuals with an enhanced risk for developing schizophrenia. Both treatment forms may reduce the risk in this population due to their specific properties: The psychotherapy can improve social skills, whereas NAC is supposed to develop its protective effects on neuronal level due to its antiinflammatory properties. The investigators will examine the preventive effects by measuring transition rates to psychosis after treatment as well as improvements in social, affective and cognitive functioning.

Conditions

Prodromal Schizophrenia

Keywords

Prodrome, CHR, Schizophrenia, prevention, N-acetylcysteine

Outcome Measures

Primary Outcomes (2)

• Transition to psychosis

  Transition to psychosis within 18 months, defined (according to EPOS1) as the presence of at least one psychotic symptom for at least one week (assessed by the SIPS).

  I. After intervention phase (26 weeks after trial start) and II. as follow-up (78 weeks after trial start)

• Psychosocial functioning

  Psychosocial functioning assessed by the SOFAS and the FROGS

  I. After intervention phase (26 weeks after trial start) and II. as follow-up (78 weeks after trial start)

Secondary Outcomes (4)

• Symptom remission

  I. After intervention phase (26 weeks after trial start) and II. as follow-up (78 weeks after trial start)

• Depression remission

  I. After intervention phase (26 weeks after trial start) and II. as follow-up (78 weeks after trial start)

• Improvement of social cognition

  I. After intervention phase (26 weeks after trial start) and II. as follow-up (78 weeks after trial start)

• Assessment of safety and tolerability

  I. After intervention phase (26 weeks after trial start) and II. as follow-up (78 weeks after trial start)

Study Arms (4)

IPPI + NAC

EXPERIMENTAL

IPPI (Integrated Preventive Psychological Intervention): 21 sessions, the first 20 sessions are scheduled weekly, the last session two weeks after session 20. Single blinded (statistician \& rater). N-Acetylcysteine (2000 mg/d, 1000 mg in the morning/evening, oral intake). Will be applied continously over 26 weeks parallel to the psychological intervention. Double-blinded.

Drug: N-Acetylcysteine; Behavioral: IPPI (Integrated Preventive Psychological Intervention)

PSM + NAC

EXPERIMENTAL

PSM (Psychological stress management): 11 sessions; the first 10 sessions will be offered biweekly, the last one 2 weeks after session 10. Single blinded (statistician \& rater). N-Acetylcysteine (2000 mg/d, 1000 mg in the morning/evening, oral intake). Will be applied continously over 26 weeks parallel to the psychological intervention. Double-blinded.

Drug: N-Acetylcysteine; Behavioral: PSM (Psychological stress management)

IPPI + Placebo

EXPERIMENTAL

IPPI (Integrated Preventive Psychological Intervention): 21 sessions, the first 20 sessions are scheduled weekly, the last session two weeks after session 20. Single blinded (statistician \& rater). Placebo will be applied continously over 26 weeks (oral intake of capsules) parallel to the psychological intervention (IPPI or PSM).

Drug: Placebo; Behavioral: IPPI (Integrated Preventive Psychological Intervention)

PSM + Placebo

ACTIVE COMPARATOR

PSM (Psychological stress management): 11 sessions; the first 10 sessions will be offered biweekly, the last one 2 weeks after session 10. Single blinded (statistician \& rater). N-Acetylcysteine (2000 mg/d, 1000 mg in the morning/evening, oral intake). Placebo will be applied continously over 26 weeks (oral intake of capsules) parallel to the psychological intervention (IPPI or PSM).

Drug: Placebo; Behavioral: PSM (Psychological stress management)

Interventions

N-Acetylcysteine DRUG

N-Acetylcysteine (2000 mg/d, 1000 mg in the morning/evening, oral intake). Will be applied continously over 26 weeks parallel to the psychological intervention (IPPI or PSM).

Also known as: NAC

IPPI + NAC; PSM + NAC

Placebo DRUG

Will be applied continously over 26 weeks (oral intake of capsules) parallel to the psychological intervention (IPPI or PSM).

IPPI + Placebo; PSM + Placebo

IPPI (Integrated Preventive Psychological Intervention) BEHAVIORAL

IPPI (Integrated Preventive Psychological Intervention): 21 sessions, the first 20 sessions are scheduled weekly, the last session two weeks after session 20. Single blinded (statistician \& rater)

IPPI + NAC; IPPI + Placebo

PSM (Psychological stress management) BEHAVIORAL

PSM (Psychological stress management): 11 sessions; the first 10 sessions will be offered biweekly, the last one 2 weeks after session 10. Single blinded (statistician \& rater).

PSM + NAC; PSM + Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 - 40 years;
• Subjects with the ability to follow study instructions and likely to attend and complete all required visits;
• Written informed consent of the subject;
• Subjects are able to speak, write and understand the German language sufficiently well (at the investigators discretion) to complete all required study procedures;
• Clinical High Risk Criteria : ESPRIT Ultra-high risk criteria (Attenuated Positive Symptoms and/or Brief Llimited Intermittend Psychotic Symptoms and/or a combination of familial risk or schizotypal disorder with a significant loss of functioning; severity assessed by the Structured Interview for Prodromal Syndromes, SIPS 5.0) and/or The Basic Symptom Criterion 'Cognitive Disturbances, COGDIS' (2/9 cognitive-perceptive basic symptoms; assessed by the Schizophrenia Proneness Instrument - Adult Version, SPI-A)

You may not qualify if:

• Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical structure;
• Simultaneously participation in another clinical trial involving administration of an investigational medicinal product within 30 days prior to clinical trial beginning. The simultaneous participation in a noninterventional clinical trial is permitted in case the subject is nevertheless able and willing to attend and complete all required visits and in case there are no other contraindications;
• Subjects with a physical or psychiatric condition which at the investigator's discretion may put the subject at other clinically significant risks than those that are defined as outcome of this study (development of a first psychotic episode, functional deterioration), may confound the trial results, or may interfere with the subject's per protocol participation in this clinical trial;
• Acute Suicidality;
• Known substance abuse or dependence according to DSM-IV-TR;
• Patients with hepatic or renal failure, or with known problems of galactose intolerance, clinically significant lactase deficiency or glucose-galactose malabsorption or histamine-intolerance;
• Subjects with known asthma bronchiale;
• Subjects with a history of gastrointestinal ulcer;
• Intake of antitussives (cough-relieving agents);
• Intake of nitroglycerin
• Females of childbearing potential, who are not using and not willing to use medically reliable methods of contraception for the entire study duration (such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices) unless they are surgically sterilized / hysterectomized or there are any other criteria considered sufficiently reliable by the investigator in individual cases.
• Having had a psychotic episode for \> 1 week (according to SIPS 5.0);
• Life time antipsychotic medication for more than 30 days (cumulative number of days) at or above minimum dosage of the '1st episode psychosis' range of DGPPN S3 Guidelines (Exception: maximum dosage for aripiprazole 5 mg/d) (Deutsche Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde, 2006);
• Any intake of antipsychotic medication (i.e., independent of duration of intake) within the past 3 months before psychopathological baseline assessments (including self-ratings and screening assessments) at or above minimum dosage of the '1st episode psychosis' range of DGPPN S3 Guidelines (Exception: maximum dosage for aripiprazole 5 mg/d) (Deutsche Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde, 2006);
• Any intake of mood stabilizers (lithium, valproate, carbamazepine, oxcabazepine, lamotrigine) \> 30 days (cumulative number of days) during the past three months or any intake during the month before psychopathological baseline assessments;

Sponsors & Collaborators

• University Hospital, Bonn: lead
• University of Cologne: collaborator
• Central Institute of Mental Health, Mannheim: collaborator
• Ludwig-Maximilians - University of Munich: collaborator
• University Hospital Tuebingen: collaborator
• Heinrich-Heine University, Duesseldorf: collaborator
• Charite University, Berlin, Germany: collaborator
• RWTH Aachen University: collaborator

Study Sites (10)

Zentralinstitut für Gesundheit Mannheim

Mannheim, Baden-Wurttemberg, 68159, Germany

Location

Universitätsklinik Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

LMU Klinikum München

München, Bavaria, 80336, Germany

Location

Uniklinik Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Uniklinikum Bonn

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Uniklinik Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

LVR Klinik Düsseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Rheinhessen Fachklinik Alzey

Alzey, Rhineland-Palatinate, 55232, Germany

Location

Charité Berlin

Berlin, 10117, Germany

Location

Berlin Vivantes

Berlin, 10967, Germany

Location

MeSH Terms

Conditions

Schizotypal Personality Disorder; Schizophrenia

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Personality Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr. Dr. Rene Hurlemann

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 11, 2017
• Study Start: September 1, 2016
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: May 9, 2022

Record last verified: 2022-05

Locations

DE (10)