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

NCT00560937 | Completed Results

• 1 other identifier: VA IRB# 00924
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Keywords

Schizophrenia; Pregnenolone; Cognition; Negative Symptoms

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• 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)

• Clinical Global Impression Scale (CGI-I)

  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)

  Change in PANSS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)

Study Arms (2)

1

ACTIVE COMPARATOR

Pregnenolone

Drug: Pregnenolone

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Pregnenolone DRUG

Pregnenolone 50 mg twice a day (BID) x 2 weeks, Pregnenolone 150 mg BID x 2 weeks, Pregnenolone 250 mg BID x 4 weeks

1

Placebo DRUG

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

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Durham VA Medical Center: lead

Study Sites (1)

Durham VAMC

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Pregnenolone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Results Point of Contact

• Title: Christine E. Marx, MD, MA
• Organization: Durham Veterans Affairs Medical Center

marx0001@mc.duke.edu

919 286-0411

Study Officials

• Christine E Marx, MD, MA

  Durham VAMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED

Study Record Dates

• First Submitted: November 19, 2007
• First Posted: November 20, 2007
• Study Start: June 1, 2005
• Primary Completion: April 1, 2006
• Study Completion: April 1, 2008
• Last Updated: August 25, 2015
• Results First Posted: December 28, 2010

Record last verified: 2015-08

Locations

US (1)