Glycine and D-Cycloserine in Schizophrenia

NCT00000372 | Withdrawn Phase 3

• 2 other identifiers: R01MH057708-02DSIR
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the effects of D-cycloserine and glycine for treating negative symptoms (such as loss of interest, loss of energy, loss of warmth, and loss of humor) which occur between phases of positive symptoms (marked by hallucinations, delusions, and thought confusions) in schizophrenics. Clozapine is currently the most effective treatment for negative symptoms of schizophrenia. Two other drugs, D-cycloserine and glycine, are being investigated as new treatments. D-cycloserine improves negative symptoms when added to some drugs, but may worsen these symptoms when given with clozapine. Glycine also improves negative symptoms and may still be able to improve these symptoms when given with clozapine. This study gives either D-cycloserine or glycine (or an inactive placebo) with clozapine to determine which is the best combination. Patients will be assigned to 1 of 3 groups. Group 1 will receive D-cycloserine plus clozapine. Group 2 will receive glycine plus clozapine. Group 3 will receive an inactive placebo plus clozapine. Patients will receive these medications for 8 weeks. Negative symptoms of schizophrenia will be monitored through the Scale for the Assessment of Negative Symptoms, Positive symptoms will be monitored through the Positive and Negative Syndrome Scale, and additionally subjects will complete the Brief Psychiatric Rating Scale and the Global Assessment Scale. An individual may be eligible for this study if he/she is 18 to 65 years old and has been diagnosed with schizophrenia.

Conditions

Schizophrenia

Keywords

Adult; Amino Acids; Cycloserine; Female; Glycine; Human; Male; N-Methylaspartate; Placebos; Schizophrenia; Amino Acids -- blood; Cycloserine -- *therapeutic use; Glycine -- *therapeutic use; Schizophrenia -- *drug therapy; Schizophrenia -- physiopathology

Outcome Measures

Primary Outcomes (1)

• Change in SANS Total Score from Baseline to Week 8

  Baseline, Week 8

Secondary Outcomes (1)

• Change in Positive and Negative Syndrome Score from Baseline to Week 8

  Baseline, Week 8

Other Outcomes (2)

• Change in Brief Psychotic Rating Scale from Baseline to Week 8

  Baseline, Week 8

• Change in Global Assessment Scale from Baseline to Week 8

  Baseline, Week 8

Study Arms (3)

Glycine

EXPERIMENTAL

The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with 30 grams of glycine in 7 ounces of lemonade twice a day in addition to clozapine treatment.

Drug: Glycine; Drug: Clozapine

Placebo

PLACEBO COMPARATOR

The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with 30 grams of placebo powder in 7 ounces of lemonade twice a day in addition to clozapine treatment.

Drug: Clozapine; Drug: Placebo

D-Cycloserine

EXPERIMENTAL

The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with D-cycloserine in addition to clozapine treatment.

Drug: D-cycloserine; Drug: Clozapine

Interventions

D-cycloserine DRUG

D-Cycloserine

Glycine DRUG

Glycine

Clozapine DRUG

D-Cycloserine; Glycine; Placebo

Placebo DRUG

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
• Score of 27 or greater on the Scale for the Assessment of Negative Symptoms (SANS)
• Treatment with stable dose of clozapine for at least 4 weeks
• Between 18 and 65 years old

You may not qualify if:

• No other antipsychotic medications in oral for for at least 3 months or in depot form for 6 months
• Current major depressive episode
• Current substance abuse diagnosis

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Freedom Trail Clinic

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Koc-Vural U, Kerimova-Kose L, Kiremitci A. Long-term clinical comparison of a resin-based composite and resin modified glass ionomer in the treatment of cervical caries lesions. Odontology. 2025 Jan;113(1):404-415. doi: 10.1007/s10266-024-00958-6. Epub 2024 Jun 5.

  PMID: 38837034 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Cycloserine; Glycine; Clozapine

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; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Donald Goff, MD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• 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: March 1, 1998
• Primary Completion: November 1, 2005
• Study Completion: November 1, 2005
• Last Updated: June 12, 2014

Record last verified: 2014-06

Locations

US (1)