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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Donald C. Goff, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00742079
First received: August 25, 2008
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: D-cycloserine
Behavioral: Cognitive Behavioral Therapy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study of Pretreatment D-cycloserine for CBT-assessment of Paranoid Delusions in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Alternative Beliefs Assessment [ Time Frame: Baseline vs. Week 1 vs. Week 2 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Predictors of Response to D-cycloserine Facilitation of CBT for Delusions in Baseline Characteristics [ Time Frame: Measured at baseline ] [ Designated as safety issue: No ]
  • Psychotic Rating Scales (PSYRATS) [ Time Frame: Measured at Baseline, Week 1 and Week 2 ] [ Designated as safety issue: No ]
  • Beck Cognitive Insight Scale (BCIS) [ Time Frame: Measured at Baseline, Week 1, and Week 2 ] [ Designated as safety issue: No ]
  • Bead Task Measuring Probabilistic Reasoning [ Time Frame: Measured at Baseline, Week 1, and Week 2 ] [ Designated as safety issue: No ]
  • Affective Salience Task [ Time Frame: Measured at Baseline, Week 1, and Week 2 ] [ Designated as safety issue: No ]
  • Select Items From the Maudsley Assessment of Delusions Scale [ Time Frame: Measured at Baseline, Week 1, and Week 2 ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: September 2006
Study Completion Date: December 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 D-cycloserine, placebo
Participants will receive D-cycloserine 1 hour before a cognitive behavioral therapy (CBT) session on Week 1, and they will receive placebo 1 hour before a CBT session on Week 2.
Drug: D-cycloserine
Single, fixed 50-mg dose of D-cycloserine administered 1 hour prior to a CBT session
Other Name: Seromycin
Behavioral: Cognitive Behavioral Therapy
One-hour talk therapy session with a trained clinician aimed at increasing cognitive flexibility by examining alternative explanations to everyday situations
Other Name: CBT
Experimental: 2 Placebo, D-cycloserine
Participants will receive placebo 1 hour before a CBT session on Week 1, and they will receive D-cycloserine 1 hour before a CBT session on Week 2.
Drug: D-cycloserine
Single, fixed 50-mg dose of D-cycloserine administered 1 hour prior to a CBT session
Other Name: Seromycin
Behavioral: Cognitive Behavioral Therapy
One-hour talk therapy session with a trained clinician aimed at increasing cognitive flexibility by examining alternative explanations to everyday situations
Other Name: CBT

Detailed Description:

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 week will receive placebo, and those who received placebo will receive D-cycloserine. The CBT sessions will attempt to increase cognitive flexibility in patients by asking them to provide alternate explanations for common situations. At screening, at the start of visits on the first and second weeks, and at a follow-up visit on the third week, participants will undergo a series of assessments, including interviews, computerized tests, and self-report measures. Belief in, preoccupation with, and distress caused by delusions, as well as degree of cognitive flexibility, will be assessed.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meets DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophrenia, paranoid subtype, based on chart review, Structured Clinical Interview for DSM-IV, and consultation with the patient's clinicians
  • Medicated with an antipsychotic agent other than clozapine at a stable dose for at least 6 weeks
  • Scores at least 3, or "moderate," on the Scale for the Assessment of Positive Symptoms global delusion rating
  • Paranoid or referential delusional content
  • Never engaged in formal CBT psychotherapy in the past

Exclusion Criteria:

  • Diagnosis of a comorbid Axis I disorder other than schizophrenia
  • Active substance abuse or dependence within 6 months
  • Significant suicidal ideation within 6 weeks
  • Pregnant or nursing
  • Unstable medical disorder
  • impaired renal clearance (creatinine <60mg/dL/min)
  • Suffering from dementia
  • Suffering from seizure disorder
  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: NCT00742079

Locations
United States, Massachusetts
MGH Schizophrenia Program - Freedom Trail Clinic
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Donald C. Goff, MD Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Donald C. Goff, MD, Director of the Schizophrenia Clinical and Research Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00742079     History of Changes
Other Study ID Numbers: P50 MH060450, 2P50MH060450-07A1, DATR A3-NSC
Study First Received: August 25, 2008
Results First Received: August 11, 2014
Last Updated: September 3, 2014
Health Authority: United States: Federal Government

Keywords provided by Massachusetts General Hospital:
Paranoid Schizophrenia
Paranoid Delusions
CBT
D-Cycloserine

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Cycloserine
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014