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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00742079

Enrollment

Registered

2008-08-27

Start date

2006-09-30

Completion date

2010-12-31

Last updated

2017-12-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizophrenia

Keywords

Paranoid Schizophrenia, Paranoid Delusions, CBT, D-Cycloserine

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 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.

Interventions

DRUGD-cycloserine

Single, fixed 50-mg dose of D-cycloserine administered 1 hour prior to a CBT session

BEHAVIORALCognitive Behavioral Therapy

One-hour talk therapy session with a trained clinician aimed at increasing cognitive flexibility by examining alternative explanations to everyday situations

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Change in Alternative Beliefs Assessment	Baseline to 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.

Secondary

Measure	Time frame	Description
Change in the Maudsley Assessment of Delusions Scale	Baseline to Week 2	This scale is a one-question item added on to the Bead Task. The one item asks for a certainty rating, from 1-3. Higher scores represent better outcomes.
Change in Psychotic Rating Scales (PSYRATS) Delusion Score	Baseline to Week 2	The Delusions subscale is a 6 item clinician administered scale, with Likert items 0-4 and range is 0-24. Higher scores represent worse outcomes
Change in Beck Cognitive Insight Scale (BCIS)	Baseline to Week 2	The BCIS is a 15-item self-report scale with Likert items 0-3. It consists of a composite score, where higher scores represent better outcomes, and there are 2 subscales: 1) Self-Reflectiveness (higher scores represent better outcomes) and 2) Self-Certainty (higher scores represent worse outcomes). The total score for each scale is the sum of the item scores that comprise it (see below). The BCIS composite index is calculated as self-reflectiveness minus self-certainty. Step 1. Score every item on the BCIS from 0 to 3 according to the following rule: Do Not Agree at All = 0, Agree Slightly = 1, Agree a Lot = 2, Agree Completely = 3 Step 2. Calculate self-reflectiveness subscale: sum items 1, 3, 4, 5, 6, 8, 12, 14, and 15. Step 3. Calculate self-certainty subscale: sum items 2, 7, 9, 10, 11, and 13. Step 4. Calculate BCIS composite index: self-reflectiveness minus self-certainty.
Change in Bead Task Score Measuring Probabilistic Reasoning	Baseline to Week 2	The Bead task is a reasoning task, where the number of beads guessed is the numeric value represented in the data. The lower end range is 1, and there is no upper range limit. Higher scores represent better outcomes.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from an urban community mental health center in Boston, MA from September 2006 to May 2010.

Pre-assignment details

31 participants were screened, 10 were excluded (7 did not meet inclusion criteria and 2 refused to participate, 1 excluded for reasons not listed in study publication)

Participants by arm

Arm	Count
1 D-cycloserine, Then Placebo Participants received 50 mg D-cycloserine 1 hour before a cognitive behavioral therapy (CBT) session on Week 1, and then received placebo 1 hour before a CBT session on Week 2.	11
2 Placebo, Then D-cycloserine Participants received placebo 1 hour before a CBT session on Week 1, and then received 50 mg D-cycloserine 1 hour before a CBT session on Week 2.	9
Total	20

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	0	1

Baseline characteristics

Characteristic	1 D-cycloserine, Then Placebo	Total	2 Placebo, Then D-cycloserine
Age, Continuous	49.2 years STANDARD_DEVIATION 9	50.2 years STANDARD_DEVIATION 10.7	51.4 years STANDARD_DEVIATION 13
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	3 Participants	1 Participants
Race (NIH/OMB) Black or African American	2 Participants	4 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	7 Participants	13 Participants	6 Participants
Region of Enrollment United States	11 participants	20 participants	9 participants
Sex: Female, Male Female	5 Participants	7 Participants	2 Participants
Sex: Female, Male Male	6 Participants	13 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 11	0 / 10
serious Total, serious adverse events	0 / 11	0 / 10

Arm	Measure	Value (MEAN)	Dispersion
D-cycloserine	Change in the Maudsley Assessment of Delusions Scale	0.05 units on a scale	Standard Deviation 0.4
Placebo	Change in the Maudsley Assessment of Delusions Scale	-0.16 units on a scale	Standard Deviation 0.37

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026