D-Cycloserine Augmentation of Cognitive Behavioral Therapy for Delusions
Condition: Schizophrenia; Schizoaffective Disorder; Delusional Disorder
MeSH terms: Schizophrenia; Psychotic Disorders; Delusions; Schizophrenia, Paranoid
Study type: Interventional
Phase: Phase 4

Summary: 
      This study is a placebo-controlled 12 week trial of DCS augmentation of once-weekly CBT
      sessions in 60 schizophrenia subjects with antipsychotic-resistant delusions. In addition to
      testing efficacy, this trial will characterize DCS effects in terms of time course and
      persistence of response and will examine DCS effects on memory consolidation and cognitive
      flexibility as possible mediators of DCS enhancement of CBT for delusions.
    

Detailed description: 
      This study consists of a placebo-controlled 12 week trial of DCS augmentation of once-weekly
      CBT sessions in 60 schizophrenia subjects with antipsychotic-resistant delusions. In addition
      to testing efficacy, this trial will characterize DCS effects in terms of time course and
      persistence of response and will examine DCS effects on memory consolidation and cognitive
      flexibility as possible mediators of DCS enhancement of CBT for delusions. This study will be
      conducted by the Schizophrenia Research Group of the NYU Langone Medical Center at One Park
      Avenue 8th Floor and the Psychiatry Outpatient Clinic of Bellevue Hospital located in New
      York, NY.

      Upon signing consent, patients will undergo screening procedures to assess eligibility. A
      diagnosis of schizophrenia, schizoaffective disorder, or delusional disorder will be
      determined by the Structured Clinical Interview for DSM IV (SCID) completed by a research
      clinician using all available clinical data and will be confirmed by consensus diagnosis. A
      comprehensive medical history and physical exam, including measurement of vital signs, will
      be performed. A psychiatric history, including diagnosis, treatment history, current
      medications, and substance use will also be performed. A research assistant will complete the
      demographics and administer the Scale for Assessment of Positive Symptoms-Delusions (SAPS-D).

      At screening only, a fasting blood sample will be obtained to perform routine laboratory
      tests including electrolytes, BUN, creatinine, liver function tests, fasting glucose,
      calcium, phosphate, magnesium, albumin and CBC with differential. Urinalysis will be
      performed to identify unstable medical illness. A urine toxicology screen will be performed
      and a urine pregnancy test will be done for women of child bearing potential.

      Subjects who meet study eligibility criteria will complete the Logical Memory Test portion of
      the Weschler Memory Scale-III (WMS-III) one week before the baseline visit.

      The baseline visit will include the following assessments: SAPS-D, Psychotic Symptom Rating
      Scales (PSYRATS), Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative
      Symptoms (SANS), Calgary Depression Rating Scale (CDRS), Clinical Global Impression (CGI),
      Heinrich's Quality of Life Scale (Heinrich's QOL), Peter's Delusion Inventory (PDI),
      Birchwood Insight Scale (BIS), Drug and Alcohol Questionnaire (DAUQ), and the Pittsburg Sleep
      Quality Index (PSQI) . At the baseline visit the following cognitive assessments will be
      administered: the Logical Memory Test of the WMS-III, The Wisconsin Card Sort Test (WCST),
      Verbal Fluency Test (VFT), and the MATRICS Consensus Cognitive Battery (MCCB).

      The clinical battery of assessments including the PSYRATS, BPRS, SANS, CDRS, CGI, and
      Heinrich's QOL will be performed on weeks 4, 8, 12, 24, and 36. The delusions section only of
      the PSYRATS will be performed on weeks 2, 3, 6, and 10. The Logical Memory Test will be
      administered on screening visit 2, baseline, week 3, and week 4. The Alternative Beliefs
      Exercise will occur on weeks 3, 4, and 12. The WCST and VFT will be given to participants at
      the baseline visit and week 12. Side effects will be assessed using the Systematic Assessment
      for Treatment Emergent Events (SAFTEE)on weeks 3, 4, 8, and 12.

      Beginning at week 1, participants will engage in hour long sessions of Cognitive Behavioral
      Therapy for delusions. This treatment course will continue weekly from week 1 until week 12
      (12 sessions).

      For the first two sessions of CBT during weeks 1 and 2, both the experimental and the placebo
      group will receive a placebo pill by mouth one hour before CBT sessions. Starting week 2, the
      placebo and experimental groups will receive their respective drugs one hour before CBT
      sessions from weeks 3-12 (placebo by mouth to placebo group, 50 mg D-cycloserine by mouth to
      experimental group).

      The primary outcome of interest in the study is the change in PSYRATS Delusions Subscale
      total score compared to placebo from baseline to week 12. Secondary outcome measures include
      changes as defined by a 20% reduction in PSYRATS Delusions Subscale total score from baseline
      after 2 weeks of DCS treatment versus placebo as well changes as defined by maintenance of a
      20% or greater reduction in the PSYRATS Delusions Subscale total score from baseline at a 3
      and 6 month follow up as compared to placebo.
    

Intervention name(s): D-Cycloserine; Placebo; Cognitive Behavioral Therapy
Intervention type(s): Drug; Other; Behavioral
Intervention description(s): Participants will receive 10 administrations of 50 mg of D-Cycloserine by mouth one hour before CBT sessions, weekly, in weeks 3-12.; Participants will receive 12 weekly administrations of placebo by mouth 1 hour before CBT sessions, from weeks 1-12.; Participants will engage in a Cognitive Behavioral Therapy treatment plan designed for psychotic delusions. The program will consist of 12 one hour sessions, once weekly from study week 1-week 12.
Other intervention name(s): Seromycin; Sugar pill; CBT
Intervention MeSH terms: Cycloserine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia; Delusions; D-Cycloserine; CBT