Clinical Trial: Using D-cycloserine to Enhance the Benefits of Cognitive Behavioral Therapy for Schizophrenia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Pilot Study of Pretreatment D-cycloserine for CBT-assessment of Paranoid Delusions in Schizophrenia

Brief Summary: This study will examine whether pretreatment with D-cycloserine before cognitive behavioral therapy can reduce impairments still present in people with stable cases of schizophrenia as well as determine which traits make schizophrenics most likely to respond to D-cycloserine treatment.

Detailed Summary:

Schizophrenia is a debilitating chronic condition that affects approximately 1 % of Americans, who experience symptoms such as hallucinations, delusions, and disorders of thought and movement. These symptoms are described as positive symptoms, because they are experienced in addition to what healthy individuals experience. Negative symptoms, which are reductions in normal functioning, and cognitive deficits, which are problems in thinking, also plague people with schizophrenia. The negative symptoms and cognitive deficits associated with schizophrenia are produced in otherwise healthy people by neurotransmitters inhibiting the glutamatergic N-methyl-d-aspartate NMDA receptors in the brain. This inhibition of NMDA receptors also causes intensification of psychotic symptoms in otherwise stabilized schizophrenic patients. The drug D-cycloserine partially excites NMDA receptors, and it has been used to help patients with anxiety disorders to overcome phobias while they are receiving cognitive behavioral therapy. This study will examine whether D-cycloserine can increase the cognitive flexibility of someone undergoing CBT and thereby enhance the therapy's ability to reduce a patient's belief in paranoid delusions, preoccupation with delusions, and related distress.

All participants will be screened to ensure proper diagnosis of schizophrenia without other conditions. Those who pass will be randomly assigned to receive either D-cycloserine first or a placebo pill first. One week after the screening, participants in the D-cycloserine group will be given the drug before a 1-hour session of simulated CBT treatment. Those in the placebo condition will receive a placebo pill before an identical session. Two weeks after the screening, both groups will be called back for another session of CBT, but the pills they receive will be switched. Those who received D-cycloserine the first wee
Sponsor: Massachusetts General Hospital

Current Primary Outcome: Alternative Beliefs Assessment [ Time Frame: Baseline vs. Week 1 vs. Week 2 ]

Number of alternative beliefs generated on the Alternative Beliefs Assessment. This assessment used nine vignettes describing social interactions: three of neutral content, three negatively-valanced, and three tailored to the patient's specific delusions. Participants were asked to generate as many explanations (alternative beliefs) as they could for each scenario, and the number of explanations produced in response to each item was recorded. Scores could range from 0 to as many explanations a person could produce (no maximum value). The total score was calculated by adding all alternative beliefs generated from each vignette. A higher number of alternative beliefs generated reflects a greater degree of cognitive flexibility.


Original Primary Outcome: Total delusion score as rated by the Scale for the Assessment of Positive Symptoms (SAPS) [ Time Frame: Measured at Weeks 1, 2, and 3 ]

Current Secondary Outcome:

  • Predictors of Response to D-cycloserine Facilitation of CBT for Delusions in Baseline Characteristics [ Time Frame: Measured at baseline ]
  • Psychotic Rating Scales (PSYRATS) [ Time Frame: Measured at Baseline, Week 1 and Week 2 ]
  • Beck Cognitive Insight Scale (BCIS) [ Time Frame: Measured at Baseline, Week 1, and Week 2 ]
  • Bead Task Measuring Probabilistic Reasoning [ Time Frame: Measured at Baseline, Week 1, and Week 2 ]
  • Affective Salience Task [ Time Frame: Measured at Baseline, Week 1, and Week 2 ]
  • Select Items From the Maudsley Assessment of Delusions Scale [ Time Frame: Measured at Baseline, Week 1, and Week 2 ]


Original Secondary Outcome:

  • Cognitive flexibility, as defined by number of alternative explanations generated in response to neutral, negative, and delusion-specific stimuli [ Time Frame: Measured at Weeks 1, 2, and 3 ]
  • Predictors of Response to D-cycloserine Facilitation of CBT for Delusions in Baseline Characteristics [ Time Frame: Measured at baseline ]
  • Psychotic Rating Scales (PSYRATS) [ Time Frame: Measured at Weeks 1, 2, and 3 ]
  • Beck Cognitive Insight Scale (BCIS) [ Time Frame: Measured at Weeks 1, 2, and 3 ]
  • Bead Task Measuring Probabilistic Reasoning [ Time Frame: Measured at Weeks 1, 2, and 3 ]
  • Affective Salience Task [ Time Frame: Measured at Weeks 1, 2, and 3 ]
  • Select Items From the Maudsley Assessment of Delusions Scale [ Time Frame: Measured at Weeks 1, 2, and 3 ]


Information By: Massachusetts General Hospital

Dates:
Date Received: August 25, 2008
Date Started: September 2006
Date Completion:
Last Updated: September 3, 2014
Last Verified: September 2014