Pilot Study of Pregnenolone Augmentation Targeting Cognitive Symptoms in Persistently Symptomatic Patients With Schizophrenia

Study Overview
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Brief Summary
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This is a pilot study of pregnenolone as an augmentation treatment for schizophrenia. The goal of this placebo-controlled study is to provide preliminary efficacy data for potential pregnenolone effects on cognitive symptoms and negative symptoms in patients with schizophrenia. Depressive symptoms and positive symptoms will also be assessed.

Detailed Description
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See brief summary

Official Title
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Pilot Study of Pregnenolone Augmentation Targeting Cognitive Symptoms in Persistently Symptomatic Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Pregnenolone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years of age, any ethnic group, either sex Diagnostic and Statistical Manual, 4th edition (DSM IV) diagnosis of schizophrenia or schizoaffective disorder Ability to participate fully in the informed consent process, or have a legal guardian able to participate in the informed consent process. Patient cohort enriched for moderate to severe cognitive symptoms (composite Brief Assessment of Cognition in Schizophrenia (BACS) score 0-3 SD below the mean). No change in antipsychotic for 8 weeks or longer. No change in antipsychotic dose for 4 weeks or longer. No change in anticholinergic, benzodiazepine, or mood stabilizer medications for 4 weeks or longer. No anticipated need to alter any of the above medications (antipsychotics, anticholinergics, benzodiazepines, or mood stabilizers) for the 10-week duration of the study. Exclusion Criteria: Unstable medical illness or neurologic illness (seizures, cerebrovascular accident); history of prostate, breast, uterine, or ovarian cancer. Use of oral contraceptives or other hormonal supplementation such as estrogen. Other concomitant medications for medical conditions will be addressed on a case-by-case base to determine if exclusionary. Active expression of suicidal or homicidal ideation. Comorbid substance dependence (other than nicotine dependence), or presenting symptoms likely substance-induced, as judged by a study physician. Female patients who are pregnant or breast-feeding. Known allergy to study medication. Drugs with a narrow therapeutic index (e.g. thioridazine, mesoridazine, ziprasidone, clozapine, etc) will be excluded as suggested by the Federal Drug Administration (FDA); patients taking these agents will not be eligible for this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: 1<br>Pregnenolone | Drug: Pregnenolone<br>* Pregnenolone 50 mg twice a day (BID) x 2 weeks, Pregnenolone 150 mg BID x 2 weeks, Pregnenolone 250 mg BID x 4 weeks<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Placebo (similar to active comparator) 50 mg BID x 2 weeks, Placebo (similar to active comparator) 150 mg BID x 2 weeks, Placebo (similar to active comparator) 250 mg BID x 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Score on the Scale for the Assessment of Negative Symptoms (SANS), p=0.048 | The SANS assesses negative symptoms in schizophrenia. The SANS consists of 21 clinical interview questions assessing negative symptoms of schizophrenia. Each question is rated on a scale of 0 (no symptoms) to 7 (severe symptoms). | SANS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward) | 
| Mean Change of Z-scores on the Brief Assessment of Cognition in Schizophrenia (BACS) | The BACS includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed. Z-scores are calculated from composite scores. Higher z-scores are indicative of better cognitive performance, lower z-scores are indicative of lower cognitive performance. Range of z-scores anticipated to be between -3 and 3. | Change in composite BACS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward) | 
| Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) | The MATRICS is a battery for the assessment of cognitive symptoms in patients with schizophrenia. Composite T-scores are calculated (T-score ranges are -20 to +80, and are normed on gender and age). Higher scores are indicative of better cognitive performance, lower scores are indicative of poorer cognitive performance. | Change in composite MATRICS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Score Change in Calgary Depression Scale for Schizophrenia (CDSS) | The CDSS is used measure to investigate depressive symptoms in schizophrenia. The measure includes 9 questions ranked from 0 (no symptoms) to 3 (severe symptoms). Range of possible scores: 0-27. | Change in CDSS scores at baseline and 8 weeks (at least 4 weeks; last observation carried forward) | 
| Clinical Global Impression Scale (CGI-I) | The CGI-I is a commonly used psychiatric scale to assess overall general improvement. The CGI-I consists of one interviewer-rated question on a scale of 1-7. Lower scores are indicative of fewer symptoms; while higher scores are indicative of more symptoms. | CGI-I scores at 8 weeks post-randomization (at least 4 weeks; last observation carried forward) | 
| Mean Score on the Positive and Negative Symptom Scale (PANSS) | The PANSS is a widely used measure with several subdomains, including positive symptoms, negative symptoms, and general psychopathology of schizophrenia. Lower scores are indicative of fewer symptoms; higher scores are indicative of more symptoms. Total PANSS scores range from 0-20. | Change in PANSS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Pregnenolone, Cognition, Negative Symptoms