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

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

Interventions

DIETARY_SUPPLEMENT

Sarcosine

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.

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA)

  collaborator NIH

• Massachusetts General Hospital

  lead OTHER

Principal Investigators

• A. Eden Evins, M.D., M.P.H. · Massachusetts General Hospital

• Marc Kaufman, Ph.D. · Mclean Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-08-31

Primary Completion

2012-07-31

Completion

2012-07-31

Countries

• United States

Study Locations