SchizophreniaPhase 3NCT00000372
Glycine and D-Cycloserine in Schizophrenia
A Phase 3 study testing D-cycloserine, Glycine and Clozapine in people with Schizophrenia, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- D-cycloserine, Glycine and Clozapine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 1998to Nov 2005
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Placebo Controlled Trial of Glycine Added to Clozapine in Schizophrenia
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.
Read more
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.
Read the detailed description
To determine if glycine produces improvement in negative symptoms and D-cycloserine produces worsening in symptoms compared to placebo, patients will undergo a double blind study of d-cycloserine and glycine treatment added to clozapine.
Clozapine is more effective for negative symptoms of schizophrenia than conventional neuroleptics, but the neurochemical actions contributing to this superior clinical efficacy remain unclear. Recent evidence points to a role for glutamatergic dysregulation in schizophrenia, as well as important differences between conventional agents and clozapine in effects upon glutamatergic systems. D-cycloserine, a partial agonist at the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor, improves negative symptoms when added to conventional agents and worsens negative symptoms when added to clozapine. High-dose glycine also improves negative symptoms and has provided preliminary evidence suggesting that glycine improves negative symptoms when added to clozapine. Serum concentrations of glycine predicted response to both high-dose glycine and D-cycloserine. Both clozapine and D-cycloserine may improve negative symptoms by activation of the glycine modulatory site of the NMDA receptor complex. Because D-cycloserine is a partial agonist, it may act as an antagonist at the glycine site in the presence of clozapine, whereas the full agonist, glycine, would not be expected to worsen negative symptoms in the presence of clozapine.
This study proposes to administer a fixed-dose of D-cycloserine, glycine, or placebo added to clozapine in 45 patients with schizophrenia. Because assessments are standardized between studies, results from this study can be compared with results from a previous study of D-cycloserine added to conventional neuroleptic.
The study was ultimately suspended before participants were enrolled, due to definitive findings indicating that pairing treatment of D-cycloserine with Clozapine resulted in worsening of negative symptoms.
- Conditions
- Schizophrenia
- Being tested
- D-cycloserine, Glycine, Clozapine, Placebo
- 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
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-cycloserineDrug
GlycineDrug
ClozapineDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: D-cycloserine; Drug: Clozapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in SANS Total Score from Baseline to Week 8
Measured: Baseline, Week 8
Secondary outcomes (1)
Change in Positive and Negative Syndrome Score from Baseline to Week 8
Measured: Baseline, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 1999 (estimated)
- Study startMar 1998
- Primary completionNov 2005
- Study completionNov 2005
Why it stopped: Pairing D-Cycloserine with Clozapine was found to worsen negative side effects in patients with Schizophrenia, so the study was suspended.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Donald C. Goff, MD, Massachusetts General Hospital
- Investigators
- Donald Goff, MD, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000372
- Sponsor's protocol ID
- R01MH057708-02
- Other IDs
- DSIR
- Status last verified
- Jun 2014
- First submitted
- 2 Nov 1999
- Last updated
- 12 Jun 2014
- Results posted
- No
Publications
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.
PubMed 38837034
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo Controlled Trial of Glycine Added to Clozapine in Schizophrenia
- ClinicalTrials.gov ID
- NCT00000372
- Acronym / sponsor ID
- R01MH057708-02
- Conditions
- Schizophrenia
- Keywords
- Adult, Amino Acids, Cycloserine, Female, Glycine, Human, Male, N-Methylaspartate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Pairing D-Cycloserine with Clozapine was found to worsen negative side effects in patients with Schizophrenia, so the study was suspended.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Mar 1998
- Primary completion
- Nov 2005 (actual)
- Study completion
- Nov 2005 (actual)
- First posted
- 3 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
To determine if glycine produces improvement in negative symptoms and D-cycloserine produces worsening in symptoms compared to placebo, patients will undergo a double blind study of d-cycloserine and glycine treatment added to clozapine.
Clozapine is more effective for negative symptoms of schizophrenia than conventional neuroleptics, but the neurochemical actions contributing to this superior clinical efficacy remain unclear. Recent evidence points to a role for glutamatergic dysregulation in schizophrenia, as well as important differences between conventional agents and clozapine in effects upon glutamatergic systems. D-cycloserine, a partial agonist at the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor, improves negative symptoms when added to conventional agents and worsens negative symptoms when added to clozapine. High-dose glycine also improves negative symptoms and has provided preliminary evidence suggesting that glycine improves negative symptoms when added to clozapine. Serum concentrations of glycine predicted response to both high-dose glycine and D-cycloserine. Both clozapine and D-cycloserine may improve negative symptoms by activation of the glycine modulatory site of the NMDA receptor complex. Because D-cycloserine is a partial agonist, it may act as an antagonist at the glycine site in the presence of clozapine, whereas the full agonist, glycine, would not be expected to worsen negative symptoms in the presence of clozapine.
This study proposes to administer a fixed-dose of D-cycloserine, glycine, or placebo added to clozapine in 45 patients with schizophrenia. Because assessments are standardized between studies, results from this study can be compared with results from a previous study of D-cycloserine added to conventional neuroleptic.
The study was ultimately suspended before participants were enrolled, due to definitive findings indicating that pairing treatment of D-cycloserine with Clozapine resulted in worsening of negative symptoms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Glycine | Experimental | Drug: Glycine, Drug: ClozapineThe 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. |
| Placebo | Placebo comparator | Drug: Clozapine, Drug: PlaceboThe 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. |
| D-Cycloserine | Experimental | Drug: D-cycloserine, Drug: ClozapineThe 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-cycloserine | Drug | D-Cycloserine |
| Glycine | Drug | Glycine |
| Clozapine | Drug | D-Cycloserine, Glycine, Placebo |
| Placebo | Drug | Placebo |
Primary outcome
Change in SANS Total Score from Baseline to Week 8
Time frame: Baseline, Week 8
1 secondary outcome
Change in Positive and Negative Syndrome Score from Baseline to Week 8
Time frame: Baseline, Week 8
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2014.
- Derived from this study: PubMed 38837034Koc-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.
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald Goff, MD principal investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing D-cycloserine, Glycine and Clozapine in people with Schizophrenia, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 12 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in SANS Total Score from Baseline to Week 8 (time frame: Baseline, Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000372, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2014.