Multimodal Prevention of First Psychotic Episode – a 2x2-Factorial Randomized Trialinvestigating the efficacy of N-Acetylcysteine (NAC) and Integrated Preventive PsychologicalIntervention (IPPI) in Subjects Clinically at High Risk for Psychosis
- Conditions
- Subjects presenting ultra-high risk (UHR) for psychosis (e.g. attenuated psychotic symptoms, brief limited intermittend psychotic symptoms or a genetic risk in combination with a decline in social functioning)
- Registration Number
- DRKS00010952
- Lead Sponsor
- Zentralinstitut für seelische Gesundheit/Central Institute of Mental Health (ZI)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 200
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)
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
11. Exclusion criteria regarding special restrictions for females: Current pregnancy or pregnancy planned within 9 months after start of medication or nursing women and
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.
Indication specific exclusion criteria:
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 asse
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Transition to psychosis within 18 months, defined (according to EPOS1) as the presence of at least one psychotic symptom for at least<br>one week (assessed by the SIPS);<br><br>2. Improvement of psychosocial functioning after 18 months (assessed by the SOFAS and the FROGS)<br><br><br>Time points:<br>I. After intervention phase (26 weeks after trial start) and<br><br>II. as follow-up (78 weeks after trial start)
- Secondary Outcome Measures
Name Time Method 1. Remission of symptomatic clinical high risk (CHR) criteria (APS/BLIPS and/or COGIDS); decrease of positive, negative and disorganization symptoms (assessed by the SIPS, BNSS score); conceptual disorganization and cognitive basic symptoms (COGDIS, SPI-A); as well as at-risk symptoms according to UHR (SPI-A);<br><br>2. remission of depressive symptoms (CDSS);<br><br>3. Improvement of social cognition (SAT-MC I & II, PoFA);<br><br>4. Assessment of safety and tolerability: Neurologic and general examination (medical history, weight, - adverse events (assessed by UKU SYMPTOM-LIST), Calgary depression rating scale items 1,2,8,9<br>(CDSS), Laboratory assessments<br><br>Time points:<br>I. After intervention phase (26 weeks after trial start) and<br><br>II. as follow-up (78 weeks after trial start)