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

NCT ID: NCT00742079

Last Updated: 2017-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2010-12-31

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.

Conditions

Schizophrenia

Keywords

Paranoid Schizophrenia; Paranoid Delusions; CBT; D-Cycloserine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

D-cycloserine

Intervention Type: DRUG

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

Cognitive Behavioral Therapy

Intervention Type: BEHAVIORAL

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

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.

Group Type: EXPERIMENTAL

D-cycloserine

Intervention Type: DRUG

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

Cognitive Behavioral Therapy

Intervention Type: BEHAVIORAL

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

Interventions

D-cycloserine

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

Intervention Type: DRUG

Cognitive Behavioral Therapy

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

Intervention Type: BEHAVIORAL

Other Intervention Names

Seromycin; CBT

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Donald C. Goff, MD

Director of the Schizophrenia Clinical and Research Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Donald C. Goff, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

MGH Schizophrenia Program - Freedom Trail Clinic

Boston, Massachusetts, United States

Countries

United States

References

Gottlieb JD, Cather C, Shanahan M, Creedon T, Macklin EA, Goff DC. D-cycloserine facilitation of cognitive behavioral therapy for delusions in schizophrenia. Schizophr Res. 2011 Sep;131(1-3):69-74. doi: 10.1016/j.schres.2011.05.029. Epub 2011 Jun 30.

Reference Type: RESULT

PMID: 21723096 (View on PubMed)

Other Identifiers

2P50MH060450-07A1

Identifier Type: NIH

Identifier Source: secondary_id

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DATR A3-NSC

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

P50MH060450

Identifier Type: NIH

Identifier Source: org_study_id

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