Pregnenolone Augmentation in the Treatment of Patients With Recent-Onset Schizophrenia

Study Overview
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Brief Summary
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Pregnenolone (PREG) is a neurosteroid, which displays multiple effects on the central nervous system, and may be beneficial in the treatment of patients with schizophrenia. Our recent 8-week, randomized, double-blind trial among patients with chronic schizophrenia and schizoaffective disorders, in which PREG versus placebo and DHEA have been added to conventional or atypical antipsychotics have yielded encouraging results with low-dose PREG (30 mg/day; ClinicalTrials.gov identifier NCT00140192; Ritsner et al., in press). The goal of the present study is to evaluate the potential role of PREG's augmentation compared to placebo in the treatment of young patients with newly diagnosed schizophrenia or schizophreniform or schizoaffective disorders. In a 8-week, randomized, double-blind placebo-controlled trial PREG (50 mg/day) or placebo capsules will be added to the stable ongoing antipsychotic treatment of 60 patients with recent-onset schizophrenia or schizophreniform or schizoaffective disorders. Participants will be assessed at baseline and after 2, 4, 6 and 8 weeks of treatment. A battery of research instruments will be used for assessment of psychopathology, cognitive functions, side effects, general functioning and quality of life. In addition blood PREG levels will be monitored at baseline and during the study. The study is powered to detect moderate between-group effects on persistent positive, negative and cognitive symptoms.

Official Title
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Pregnenolone Augmentation in the Treatment of Patients With Recent-Onset Schizophrenia: an 8-week, Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorders

Intervention / Treatment
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* Dietary Supplement: Pregnenolone
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-40 years of age, any ethnic group, either sex. DSM-IV criteria for schizophrenia, schizophreniform or schizoaffective disorders (36). Duration of illness less than 5 years since onset first psychotic episode. Subjects entering the study must score at least 4 on the Clinical Global Impression Scale. At least two weeks of ongoing treatment with current antipsychotic agents during the pre-treatment stabilization period. Stable symptoms throughout the 2-week pre-treatment stabilization period. Clinical stability is defined as two consecutive weekly CGI ratings with no change in score, and with no more than a 20% change in PANSS total score. No change in anticholinergic, benzodiazepine, or mood stabilizer medications for the pre-treatment stabilization period. No anticipated need to alter any of the above medications (antipsychotics, anticholinergics, benzodiazepines, or mood stabilizers) for the 8-week duration of the study. Ability to participate fully in the informed consent process, or have a legal guardian able to participate in the informed consent process. Exclusion Criteria: Evidence of serious neurologic or endocrine disorder, for example severe head trauma, seizure disorder, dementia, Cushings disease, or thyroid disorder, mental retardation, alcohol or drug abuse, substance dependence (other than nicotine dependence), or presenting symptoms likely substance-induced, as judged by a study physician. Unstable medical illness or neurologic illness (seizures, CVA); history of prostate, breast, uterine, or ovarian cancer. Pregnant women, use of oral contraceptives or other hormonal supplementation such as estrogen. Current active suicidal and/or homicidal ideation, intent, or plan. Known allergy to study medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Pregnenolone<br>50 mg/day | Dietary Supplement: Pregnenolone<br>* 50 mg, caps.<br>|
| Placebo Comparator: 2 Placebo<br>1 caps. | Dietary Supplement: Placebo<br>* caps<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Clinical Global Impression Scale (CGI-S) The Positive and Negative Syndrome Scale (PANSS) The Scale for the Assessment of Negative Symptoms (SANS) |  | baseline, 2, 4, 6, and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Assessment of Functioning |  | baseline, 2, 4, 6, and 8 weeks | 
| The Cambridge Neuropsychological Test Automated Battery (CANTAB) |  | baseline, 4 and 8 weeks | 
| Extrapyramidal Symptom Rating Scale |  | baseline, 2, 4, 6, and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Neurosteroids, Pregnenolone, Augmentation