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

NCT ID: NCT03149107

Last Updated: 2022-05-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-01
• Study Completion Date: 2021-01-31

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.

Detailed Description

Psychotic disorders are among the most expensive brain-related disorders in Europe. This is mainly due to their onset early in life and their long-term disabling courses. Current treatments fail to improve most influential factors such as social-cognitive deficits. Prevention is recognized as one of the key strategies to fight these deteriorating outcomes and is expected to significantly reduce both, the societal costs as well as the immense burden for the patients and for their families. Recent meta-analyses indicate promising preventive effects of both pharmacological and cognitive-behavioural interventions. Yet, reported transition rates are still too high. Clinical evidence suggests that disturbances of social functioning predict conversion to psychosis. Neurobiological evidence implicates glutamatergic dysfunction and redox imbalance in the pathophysiology of schizophrenia. The investigators hypothesize that interventions targeting (i) social functioning and (ii) glutamatergic / oxidative pathways already in at-risk states would significantly reduce transition rates. To test these hypotheses, our study is designed as a randomized, placebo-controlled, 18-month trial (six months of intervention plus 12 months of follow-up), involving 200 subjects at-risk for psychosis. Specifically, the investigators will compare the preventive effects of a cognitive-behavioural and social-cognitive intervention to a pharmacological intervention (IPPI) with Acetylcysteine, a drug with a proglutamatergic, neuroprotective and anti-inflammatory profile in a 2x2 factorial design. The results of our planned study are expected to provide new and well tolerated interventions, thus hopefully helping to achieve the major goal of individualized prevention, and, consequently, lower the individual and societal burden of psychosis.

Conditions

Prodromal Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

IPPI + NAC

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.

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: 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).

IPPI (Integrated Preventive Psychological Intervention)

Intervention Type: 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)

PSM + NAC

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.

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: 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).

PSM (Psychological stress management)

Intervention Type: 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).

IPPI + Placebo

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).

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

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

IPPI (Integrated Preventive Psychological Intervention)

Intervention Type: 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)

PSM + Placebo

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).

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

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

PSM (Psychological stress management)

Intervention Type: 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).

Interventions

N-Acetylcysteine

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).

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

IPPI (Integrated Preventive Psychological Intervention)

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)

Intervention Type: BEHAVIORAL

PSM (Psychological stress management)

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).

Intervention Type: BEHAVIORAL

Other Intervention Names

NAC

Eligibility Criteria

Inclusion Criteria

1. Age 18 - 40 years;

2. Subjects with the ability to follow study instructions and likely to attend and complete all required visits;

3. Written informed consent of the subject;

4. Subjects are able to speak, write and understand the German language sufficiently well (at the investigators discretion) to complete all required study procedures;

Specific inclusion criterion:

5. 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)

Exclusion Criteria

1. Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical structure;

2. 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;

3. 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;

4. Acute Suicidality;

5. Known substance abuse or dependence according to DSM-IV-TR;

6. Patients with hepatic or renal failure, or with known problems of galactose intolerance, clinically significant lactase deficiency or glucose-galactose malabsorption or histamine-intolerance;

7. Subjects with known asthma bronchiale;

8. Subjects with a history of gastrointestinal ulcer;

9. Intake of antitussives (cough-relieving agents);

10. Intake of nitroglycerin

12. 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.

13. Having had a psychotic episode for > 1 week (according to SIPS 5.0);

14. Having symptoms relevant for inclusion potentially arising from a known general medical disorder;

15. 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);

16. 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);

17. 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;

18. Intake of antidepressants during the past 30 days before psychopathological baseline assessments;

19. Intake of benzodiazepines for more than 2 consecutive days during the past 5 days before psychopathological baseline assessments;

20. Psychotherapeutic intervention during the past 30 days before psychopathological baseline assessments;

21. Any past psychotherapeutic treatment targeting specifically psychotic symptoms or its prevention.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cologne

OTHER

Sponsor Role: collaborator

Central Institute of Mental Health, Mannheim

OTHER

Sponsor Role: collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role: collaborator

RWTH Aachen University

OTHER

Sponsor Role: collaborator

University Hospital, Bonn

OTHER

Sponsor Role: lead

Responsible Party

Rene Hurlemann

Professor Dr. Dr. Rene Hurlemann

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Zentralinstitut für Gesundheit Mannheim

Mannheim, Baden-Wurttemberg, Germany

Universitätsklinik Tübingen

Tübingen, Baden-Wurttemberg, Germany

LMU Klinikum München

München, Bavaria, Germany

Uniklinik Aachen

Aachen, North Rhine-Westphalia, Germany

Uniklinikum Bonn

Bonn, North Rhine-Westphalia, Germany

Uniklinik Köln

Cologne, North Rhine-Westphalia, Germany

LVR Klinik Düsseldorf

Düsseldorf, North Rhine-Westphalia, Germany

Rheinhessen Fachklinik Alzey

Alzey, Rhineland-Palatinate, Germany

Charité Berlin

Berlin, , Germany

Berlin Vivantes

Berlin, , Germany

Countries

Germany

Other Identifiers

University Hospital, Bonn

Identifier Type: -

Identifier Source: org_study_id