Study of a Neurocognition Enhancing Agent in Patients With Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of this study is to determine whether pregnenolone will demonstrate significant
      improvements in cognitive functioning and negative symptoms compared to patients receiving
      placebo.
    

Detailed description: 
      Aims:

      Schizophrenia is one of the most disabling disorders to afflict mankind. Despite the low
      lifetime prevalence of schizophrenia (1% world-wide), it has an enormous burden in both
      economic cost and human suffering. There is currently no cure for schizophrenia and its cause
      is not well understood. Patients with schizophrenia also suffer from negative symptoms (loss
      of drive, apathy, poverty of speech) and severe cognitive impairments especially with memory,
      attention, processing of information - the latter of which is most robustly correlated with
      their role functioning in the community. Addressing these impairments with effective
      interventions is thus critically important but at this present moment, there is no effective
      treatment. Recent emerging data from animal studies and a pilot study on small group of
      patients with schizophrenia suggest that neurosteroids such as pregnenolone may be relevant
      to schizophrenia pathophysiology and treatment of neurocognitive impairments. This study will
      be a 10-week randomised double-blind placebo-controlled trial of the efficacy and safety of
      pregnenolone. Our hypothesis is patients with schizophrenia randomized to pregnenolone will
      demonstrate significant improvements in cognitive functioning and negative symptoms compared
      to patients receiving placebo. The primary aims of the study are to demonstrate the efficacy
      of pregnenolone in comparison to placebo in patients with schizophrenia which are assessed by
      changes (from baseline) in the composite score of the MATRICS Consensus Cognitive Battery
      (MCCB), BACS and the Scale for Assessment of Negative Symptoms (SANS). Changes in
      functionality will be assessed by the University of California Performance Based Skills
      Assessment (UPSA). Safety will be assessed with laboratory tests, well established scales for
      side effects as well as with a side-effects checklist.

      Objectives:

      To demonstrate the efficacy of pregnenolone in comparison to placebo in patients with
      schizophrenia and with cognitive impairment from randomization (Week 2) to Week 10 by using
      MATRICS Consensus Cognitive Battery, BACS, Scale for Assessment of Negative Symptoms,
      Performance Based Skills Assessment - Brief Version and Clinical Global Impression
      -Improvement (CGI-I).Additional safety data on pregnenolone in patients with schizophrenia
      will be provided.

      Methodology:

      The proposed study is a single-site, randomized, double blind placebo-controlled comparison
      of adjunctive pregnenolone and placebo. A total sample will consist of 120 clinically stable
      inpatients and outpatients with DSM IV schizophrenia, with 60 subjects randomized to each
      group. A best estimate diagnostic approach will be utilized, in which information from the
      Structured Clinical Interview for DSM-IV will be supplemented by information from family
      informants, previous psychiatrists, and medical records to generate a diagnosis. There will
      be a 2 week, single-blind placebo lead-in evaluation phase, in which subjects will undergo
      baseline diagnostic and medical testing, including a physical examination, Electrocardiogram
      (ECG), Complete Blood Counts (CBC), complete metabolic panel, urine toxicology, and
      urinalysis. The study is designed to confirm the pilot study results (n=9 per group; total of
      18 patients of 21 randomized who completed at least 4 weeks of treatment) in a larger
      clinical trial (n=60 per group, 120 patients total). Identical to our pilot study, patients
      will be seen for a total of 6 study visits (every two weeks). The placebo arm is essential as
      there are no standard therapies for cognitive defects as yet.

      Potential Benefits:

      While patients may not personally be helped by taking part in this study, their participation
      may lead to knowledge that will help better understand the illness. It may also lead to
      better treatment for cognitive deficits and negative symptoms in schizophrenia.

      Potential Risks:

      Obtaining blood can cause pain, bleeding, bruising, or swelling at the site of the needle
      prick. There is a risk that some questions on the questionnaires might upset the patients or
      cause psychological distress. There are no known severe risks that had been associated with
      taking pregnenolone.
    

Intervention name(s): Pregnenolone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Pregnenolone 50 mg BID x 14 days, followed by Pregnenolone 300 mg per day for 14 days (200 mg qAM and 100 mg qPM), followed by Pregnenolone 500 mg per day for the remainder of the 8-week trial (300 mg qAM and 200 mg qPM); Placebo 50 mg BID x 14 days, followed by Placebo 300 mg per day for 14 days (200 mg qAM and 100 mg qPM), followed by Placebo 500 mg per day for the remainder of the 8-week trial (300 mg qAM and 200 mg qPM)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia; Pregnenolone; Neurocognition