Trial of D-Cycloserine in Schizophrenia

NCT00000371 | Completed Phase 3 Results

• 1 other identifier: R01MH054245-01A2
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic and serotonergic function in serum and cerebrospinal fluid. To determine if negative symptoms and cognitive function improve over time, if these improvements meaningfully impact quality of life factors, if they correlate with markers of neuronal function, and if subpopulations can be identified according to response. Dysfunction of glutamatergic neuronal systems has recently been implicated in the pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the NMDA receptor can reproduce in normals the positive symptoms, negative symptoms, and cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, will reduce symptoms in schizophrenia. Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month, fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive to prefrontal cortical function, is administered. Blood is obtained at several time points and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA, and 5HIAA.

Conditions

Schizophrenia

Keywords

Adult; Cognition; Cycloserine; Dopamine; Female; Glutamic Acid; Human; Male; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Serotonin; Quality of Life; Cycloserine -- *therapeutic use; Dopamine -- blood; Dopamine -- cerebrospinal fluid; Glutamic Acid -- blood; Glutamic Acid -- cerebrospinal fluid; Serotonin -- blood; Serotonin -- cerebrospinal fluid

Outcome Measures

Primary Outcomes (1)

• Scale for the Assessment of Negative Symptoms (SANS)

  The slope of SANS total score from baseline to week 8 in the treatment and placebo groups on the scale for the assessment of negative symptoms (SANS) total score. Total SANS scores range from 0-100. The SANS is comprised of 5 subscores: Affective Flattening or Blunting (score range 0-35), Alogia (score range 0-20), Avolition-Apathy (score range 0-15), Anhedonia-Asociality (score range 0-20), and Attention (0-10). For each scale, the higher the score the more prominent the negative symptoms were. The slopes were obtained by plotting the group SANS total score mean for treatment vs. placebo on Baseline, Week 4, and Week 8 and performing a random slopes model.

  Baseline, Week 4, Week 8

Study Arms (2)

D-Cycloserine

EXPERIMENTAL

Subjects were given 50 mg/day of D-Cycloserine for 24 weeks

Drug: D-cycloserine

Placebo

PLACEBO COMPARATOR

Participants were given 50 mg/day of Placebo for 24 weeks.

Drug: Placebo

Interventions

D-cycloserine DRUG

50 mg/daily by mouth

Also known as: Cycloserine

D-Cycloserine

Placebo DRUG

50 mg/day of placebo by mouth

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Schizophrenia as per DSM IV criteria
• Have been treated for at least 6 months with any conventional neuroleptic
• Have prominent negative symptoms as defined by a total score of 40 or greater on the scale for the assessment of negative symptoms (SANS)

You may not qualify if:

• Active alcohol or drug abuse
• Unstable Medical Illness, seizure disorder, or other serious neurological disorder
• Pregnant or Nursing
• Unable to complete a cognitive battery

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Related Publications (1)

• Goff DC, Herz L, Posever T, Shih V, Tsai G, Henderson DC, Freudenreich O, Evins AE, Yovel I, Zhang H, Schoenfeld D. A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients. Psychopharmacology (Berl). 2005 Apr;179(1):144-50. doi: 10.1007/s00213-004-2032-2. Epub 2004 Oct 21.

  PMID: 15502972 RESULT

MeSH Terms

Conditions

Schizophrenia

Interventions

Cycloserine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

A biased sample may have been produced by restricting the analysis to patients with prominent negative symptoms receiving conventional agents (less compliant with study medication). Additionally, Adverse Event data was lost for the study.

Results Point of Contact

• Title: Dr. Donald Goff
• Organization: Freedom Clinic Trail, Massachusetts General Hospital

goff@psych.mgh.harvard.edu

617-921-7899

Study Officials

• Donald Goff, MD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Schizophrenia Clinical and Research Program

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: November 3, 1999
• Study Start: August 1, 1996
• Primary Completion: April 1, 2002
• Study Completion: April 1, 2002
• Last Updated: September 10, 2014
• Results First Posted: September 10, 2014

Record last verified: 2014-09