Pregnenolone for Cognitive and Negative Symptoms in Schizophrenia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development
ClinicalTrials.gov Identifier:
NCT00728728
First received: August 1, 2008
Last updated: October 13, 2015
Last verified: October 2015
  Purpose
This study will investigate adjunctive pregnenolone for cognitive symptoms and negative symptoms in patients with schizophrenia and schizoaffective disorder.

Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: Dietary Supplement: Pregnenolone
Dietary Supplement: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pregnenolone for Cognitive and Negative Symptoms in Schizophrenia

Resource links provided by NLM:


Further study details as provided by VA Office of Research and Development:

Primary Outcome Measures:
  • MATRICS Consensus Cognitive Battery (MCCB) [ Time Frame: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10) ] [ Designated as safety issue: No ]

    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.


  • University of California Performance-based Skills Assessment (UPSA) [ Time Frame: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10) ] [ Designated as safety issue: No ]
    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.

  • Brief Assessment of Cognition in Schizophrenia (BACS) [ Time Frame: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10) ] [ Designated as safety issue: No ]
    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).

  • Scale for the Assessment of Negative Symptoms(SANS) [ Time Frame: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10) ] [ Designated as safety issue: No ]
    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. Assessments are conducted on a six-point scale (0=not at all to 5=severe).[1]


Secondary Outcome Measures:
  • The Calgary Depression Scale for Schizophrenia (CDSS), Positive and Negative Syndrome Scale (PANSS),Clinical Global Impressions (CGI) Scale [ Time Frame: Prospective, outcome measures collected over 10 week trial period. ] [ Designated as safety issue: No ]
    The CDSS assesses the level of depression in schizophrenia by measuring nine items on a 0 (absent) to 3 (severe) scale.

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10) ] [ Designated as safety issue: No ]
    The PANSS measures positive and negative symptoms of schizophrenia through administering a structured interview. After the interview, 25 PANSS items are rated 1 (absent) to 7 (extreme). These items are organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation.

  • Clinical Global Impressions (CGI) Scale [ Time Frame: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10) ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 88
Study Start Date: December 2009
Estimated Study Completion Date: December 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
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
Dietary Supplement: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00728728

Locations
United States, North Carolina
Durham VA Medical Center, Durham, NC
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Principal Investigator: Christine Marx, MD MA Durham VA Medical Center, Durham, NC
  More Information

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT00728728     History of Changes
Obsolete Identifiers: NCT00639886
Other Study ID Numbers: MHBB-012-07F 
Study First Received: August 1, 2008
Last Updated: October 13, 2015
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by VA Office of Research and Development:
pregnenolone
schizophrenia
cognitive
positive symptom
negative symptom
placebo control

Additional relevant MeSH terms:
Schizophrenia
Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders

ClinicalTrials.gov processed this record on July 25, 2016