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

Not Applicable

Completed

Conditions: Schizophrenia

Interventions: Drug: Placebo
Drug: Pregnenolone

Registration Number: NCT00560937

Lead Sponsor: Durham VA Medical Center

Brief Summary: 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: See brief summary

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Placebo
1	Pregnenolone	Pregnenolone

Primary Outcome Measures

Name	Time	Method
Mean Score on the Scale for the Assessment of Negative Symptoms (SANS), p=0.048	SANS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)	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).
Mean Change of Z-scores on the Brief Assessment of Cognition in Schizophrenia (BACS)	Change in composite BACS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)	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.
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)	Change in composite MATRICS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)	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.

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impression Scale (CGI-I)	CGI-I scores at 8 weeks post-randomization (at least 4 weeks; last observation carried forward)	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.
Mean Score on the Positive and Negative Symptom Scale (PANSS)	Change in PANSS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)	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.
Mean Score Change in Calgary Depression Scale for Schizophrenia (CDSS)	Change in CDSS scores at baseline and 8 weeks (at least 4 weeks; last observation carried forward)	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.