Pregnenolone for Cognitive and Negative Symptoms in Schizophrenia

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00728728

Enrollment

Registered

2008-08-06

Start date

2009-12-31

Completion date

2015-12-31

Last updated

2017-02-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizoaffective Disorder, Schizophrenia

Keywords

pregnenolone, schizophrenia, cognitive, positive symptom, negative symptom, placebo control

Brief summary

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

Interventions

DRUGDietary 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.

DIETARY_SUPPLEMENTPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

21 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
MATRICS Consensus Cognitive Battery (MCCB)	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)	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.
University of California Performance-based Skills Assessment (UPSA)	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)	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.
Brief Assessment of Cognition in Schizophrenia (BACS)	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)	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.
Scale for the Assessment of Negative Symptoms(SANS)	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)	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.

Secondary

Measure	Time frame	Description
Positive and Negative Syndrome Scale (PANSS)	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)	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.
Clinical Global Impressions (CGI) Scale	Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)	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.
The Calgary Depression Scale for Schizophrenia (CDSS)	Prospective, outcome measures collected over 10 week trial period.	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Arm 1: Pregnenolone 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.	42
Arm 2: Placebo Placebo control group	46
Total	88

Baseline characteristics

Characteristic	Arm 2: Placebo	Total	Arm 1: Pregnenolone
Age, Continuous	51.6 years STANDARD_DEVIATION 8.4	51.7 years STANDARD_DEVIATION 8.4	51.9 years STANDARD_DEVIATION 8.5
Gender Female	7 Participants	13 Participants	6 Participants
Gender Male	39 Participants	75 Participants	36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	36 Participants	63 Participants	27 Participants
Race (NIH/OMB) More than one race	1 Participants	4 Participants	3 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	9 Participants	21 Participants	12 Participants
Region of Enrollment United States	46 participants	88 participants	42 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	31 / 42	38 / 46
serious Total, serious adverse events	3 / 42	4 / 46

Outcome results

Primary

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.