Pregnenolone for Cognitive and Negative Symptoms in Schizophrenia

This study will investigate adjunctive pregnenolone for patients with schizophrenia and schizoaffective disorder.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Dietary supplement: Placebo; Drug: Dietary Supplement: Pregnenolone

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Durham VA Medical Center, Durham, NC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis: DSM-IV/DSM-IV TR schizophrenia or schizoaffective disorder;
• Gender: Males and Females;
• Age: 21-65;
• Caucasian or Non Caucasian;
• Capable of providing informed consent;
• Duration of illness equal to or greater than one year;
• No change in antipsychotic medication in the previous eight weeks, no change in antipsychotic dose in the previous four weeks;
• No benzodiazepine use in the past twelve hours prior to cognitive testing;
• The patient cohort will be enriched for cognitive symptoms (Composite BACS scores = 0-3 standard deviations below the mean, assessed at the screening visit).

Exclusion Criteria:

• Subjects with a DSM-IV/DSM-IV TR diagnosis of alcohol or substance dependence (other than nicotine) within the last month;

• Subjects with a history of significant head injury/trauma, as defined by one or more of the following:

  • Loss of consciousness (LOC) for more than 1 hour,
  • Recurring seizures resulting from the head injury,
  • Clear cognitive sequelae of the injury,
  • Cognitive rehabilitation following the injury;
• Subjects with unstable medical illness or neurological illness (seizures, CVA);
• Patients with hormone-sensitive tumors (such as breast, uterine, or prostate cancer);
• Clinically significant abnormalities in physical examination , ECG, or laboratory assessments;
• Pregnant women or women of child-bearing potential, who are either not surgically-sterile or not using appropriate methods of birth control (serum beta-human chorionic gonadotropin [HCG] will be performed at baseline, 4 weeks, and 8 weeks to exclude pregnancy);
• Women who are breast-feeding;
• Electroconvulsive therapy (ECT) treatment within the last 3 months;
• Use of oral contraceptives or other hormonal supplementation such as estrogen. Although early studies suggested no effects on menstrual cycle, alterations in downstream metabolites of pregnenolone (such as estradiol) could theoretically impact the efficacy of oral contraceptives and/or estrogen replacement. Similarly, it is theoretically possible that pregnenolone could be metabolized to other steroids, resulting in hair, skin, or other steroid-related changes. Since we have determined in our prior study that pregnenolone administration does not result in downstream elevations in DHEA, DHEAS, estradiol, or testosterone, these possibilities may be unlikely;
• Current active suicidal and/or homicidal ideation, intent, or plan;
• Known allergy to study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Arm 1: Pregnenolone; Pregnenolone	Drug: Dietary Supplement: Pregnenolone; Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
PLACEBO_COMPARATOR: Arm 2: Placebo; Placebo	Dietary supplement: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MATRICS Consensus Cognitive Battery (MCCB)	The MATRICS Consensus Cognitive Battery (MCCB) is a standardized battery for use with adults with schizophrenia and related disorders to measure cognition in these individuals. The MCCB consists of ten individually administered test which measure speed of processing, attention/vigilance, nonverbal working memory, verbal working memory, verbal learning, visual learning, reasoning and problem solving and social cognition. The primary raw scores are entered into the MCCB Computer Scoring Program which then generates the corresponding T-scores and percentiles, along with a graphic profile of the scores for each of the seven cognitive domains. Higher scores indicate better performance.	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)
University of California Performance-based Skills Assessment (UPSA)	The UCSD Performance-based Skills Assessment (UPSA) is a measure of Functional Capacity and assesses skills involved in community tasks. It is composed of five subdomains (comprehension and planning, finance, communication, mobility and house management) when combined, measures functional capacity. The comprehension and planning subdomain ranges from 0 to 14, the finance subdomain ranges from 0 to 11, the communication subdomain ranges from 0 to 12, the mobility subdomain ranges from 0 to 9, and the house management subdomain ranges from 0 to 4. Then a medication management score of 0 to 37 is added. In total, the Assessment is thus scored on a 0 to 87 scale, with higher scores indicating better performance.	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)
Brief Assessment of Cognition in Schizophrenia (BACS)	The Brief Assessment of Cognition in Schizophrenia (BACS) captures those domains of cognition that are the most severely affected in patients with schizophrenia and the most strongly correlated with functional outcome. The domains of cognitive function assessed and the associated tests include: Verbal Memory & Learning (Verbal Memory), Working Memory (Digit Sequencing), Motor Function (Token Motor Task), Verbal Fluency (Semantic and Letter Fluency), Speed of Processing (Symbol Coding), and Executive Function (Tower of London). These domains are then converted to Z scores compared to standardized scoring scales, with higher scores representing better performance.	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)
Scale for the Assessment of Negative Symptoms(SANS)	The Scale for the Assessment of Negative Symptoms (SANS) is an assessment used to obtain clinical ratings of negative symptoms in patients with schizophrenia. The SANS assesses five symptom complexes. They are: affective blunting; alogia (impoverished thinking); avolition/apathy; anhedonia/asociality; and disturbance of attention. 24 assessments are conducted on a six-point scale (0=not at all to 5=severe) each, for a total scoring range of 0-120. Lower scores represent better performance.	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Calgary Depression Scale for Schizophrenia (CDSS)	The CDSS assesses the level of depression in schizophrenia by measuring nine items on a 0 (absent) to 3 (severe) scale each. Thus, the total score range is 0 to 27. Lower scores represent better outcomes.	Prospective, outcome measures collected over 10 week trial period.
Positive and Negative Syndrome Scale (PANSS)	The PANSS measures positive and negative symptoms of schizophrenia through administering a structured interview. After the interview, 25 PANSS items are each rated 1 (absent) to 7 (extreme). These items are organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation. The combination of the 25 items produces a total score range of 25-175, and lower scores represent better outcomes.	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)
Clinical Global Impressions (CGI) Scale	The CGI scale provides a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. The CGI comprises two companion one-item measures evaluating the severity of psychopathology from 1 to 7 and change from the initiation of treatment on a similar seven-point scale. Thus, scores range from 2 to 14, with lower scores representing better outcomes.	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)

Collaborators and Investigators

• Sponsor: VA Office of Research and Development

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (ACTUAL): March 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: August 1, 2008
• First Submitted That Met QC Criteria: August 5, 2008
• First Posted (ESTIMATE): August 6, 2008

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2017
• Last Update Submitted That Met QC Criteria: December 19, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: schizophrenia; cognitive; placebo control; pregnenolone; positive symptom; negative symptom
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: MHBB-012-07F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED