A Study of the Effects of Sarcosine on Symptoms and Brain Glycine Levels in People With Schizophrenia

NCT00538070 | Completed DMC

• 5 other identifiers: 1R01DA022276-011R01DA022276#2007-P-000416/1R01DA022276DPMC
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

Brief Summary

The NMDA receptor has been identified as having a role in substance use disorders as well as in schizophrenia. One example of the former is nicotine's effect on dopaminergic activity not only by increasing the release of dopamine in the Midbrain reward centers, but also through less direct mechanisms affecting alpha-7 nicotinic receptors, NMDA receptors, and Glycine, a co-agonist for the NMDA receptors. In terms of schizophrenia, it has been hypothesized that NMDA receptor hypofunction plays a role in the mechanism for negative symptoms and cognitive dysfunction in these patients. The NMDA hypofunction may be reversed with increased synaptic glycine availability. Sarcosine, or n-methyl-glycine, is a GlyT-1 and System A transport inhibitor actions which could be expected to increase the availability of glycine, in the synaptic space. Sarcosine is a dietary supplement which could be found in several food items such as egg yolks and turkey. Our collaborative team has developed a novel, non-invasive magnetic resonance spectroscopy (MRS) technique for measuring brain glycine changes that allows us to study glycine homeostasis. The purpose of this study is to explore the effect of sarcosine (n-methyl-glycine) on brain glycine concentrations. It is our hypothesis that oral sarcosine, at a dose of 2 grams per day, will be well tolerated and associated with increased brain glycine concentrations. It is our secondary exploratory hypothesis that increases in brain glycine will be associated with behavioral signs of increased NMDA and dopamine activity. This modulation could have future therapeutic potential for disorders of hedonic and cognitive function.

Conditions

Schizophrenia

Keywords

Sarcosine; Glycine; Magnetic Resonance Spectroscopy; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Increases in brain glycine concentration as measured by magnetic resonance spectroscopy

  baseline and endpoint

Study Arms (2)

Placebo

PLACEBO COMPARATOR

You will receive two grams of placebo per day. You will take two 500 mg placebo capsules twice per day, once in the morning and once in the evening, every day for six weeks. You can take the pills with or without food. You should continue to take all your other medications throughout the study.

Dietary Supplement: Sarcosine

Sarcosine

EXPERIMENTAL

You will receive two grams of sarcosine per day. You will take two 500 mg capsules twice per day, once in the morning and once in the evening, every day for six weeks. You can take the pills with or without food. You should continue to take all your other medications throughout the study.

Dietary Supplement: Sarcosine

Interventions

Sarcosine DIETARY_SUPPLEMENT

You will receive two grams of sarcosine or placebo per day. Each capsule will contain 500 mg of sarcosine or placebo. You will take two capsules twice per day, once in the morning and once in the evening, every day for six weeks. You can take the pills with or without food. You should continue to take all your other medications throughout the study.

Also known as: glycine transport inhibitor

Placebo; Sarcosine

Eligibility Criteria

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

You may qualify if:

• Women and men aged 18-65 with DSM-IV diagnosis of schizophrenia or schizoaffective disorder by diagnostic interview and chart review.
• Clinically stable on a stable dose of antipsychotic medication for at least one month, no current active suicidal ideation.
• Competent to provide informed consent.
• Women of childbearing age must have a negative pregnancy test at screening and agree to use an approved form of contraception throughout the study.
• Screening labs within normal limits for age and gender except for liver function tests as specified below.

You may not qualify if:

• Diagnosis of bipolar disorder, dementia, neurodegenerative disease, or other organic mental disorder.
• History of seizure disorder or CNS tumor.
• Liver function tests elevated over twice normal.
• Bulimia, or major depressive disorder within the last 6 months.
• Life-threatening arrhythmia, cerebro-vascular, or cardiovascular event within 6 months. Current serious unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease such that hospitalization for treatment of that illness is likely within the next 2 months. Lifetime history of multiple head injuries with neurological sequelae or a single severe head injury with lasting neurological sequelae.
• Use of investigational medication within 30 days of enrollment.
• Use of clozapine.
• Substance use disorder other than nicotine or caffeine in the last 6 months (by self report and salivary drug and alcohol screen).
• Posing a current risk of homicide or suicide.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

McLean Hospital, Brain Imaging Center

Belmont, Massachusetts, 02478, United States

Location

MGH Center for Addiction Medicine

Boston, Massachusetts, 02114, United States

Location

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MeSH Terms

Conditions

Schizophrenia

Interventions

Sarcosine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

N-substituted Glycines; Glycine; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• A. Eden Evins, M.D., M.P.H.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Marc Kaufman, Ph.D.

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry and Director of the MGH Center for Addiction Medicine

Study Record Dates

• First Submitted: October 1, 2007
• First Posted: October 2, 2007
• Study Start: August 1, 2007
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: September 18, 2012

Record last verified: 2012-09

Locations

US (2)