A Study of the Effects of Sarcosine on Symptoms and Brain Glycine Levels in People With Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

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.
    

Detailed description: 
      Research subjects will undergo a screening visit at the Massachusetts General Hospital Center
      for Addiction Medicine. If they meet inclusion criteria, they will be invited for the
      baseline visit when they will have their first MRS and will begin taking the study
      drug/placebo. The randomization will be done in blocks of four. The study drug/placebo is
      prescribed to take 2 capsules of 500 mg each, two times per day, with or without food. They
      will continue weekly visits for six weeks and will receive new supplies of the study
      drug/placebo on weeks 2 and 4. On week 6, they will have the second MRS. On weeks 8 and 16,
      subjects will undergo follow up visits. On several of these visits, study staff will assess
      for the presence of adverse events (with the UKU instrument), cigarettes use (with carbon
      monoxide monitoring), and abnormal involuntary movements (with the abnormal involuntary
      movement scale, the barnes akathisia scale, and the sympson angus scale).
    

Intervention name(s): Sarcosine
Intervention type(s): Dietary Supplement
Intervention description(s): 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.
Other intervention name(s): glycine transport inhibitor
Intervention MeSH terms: Glycine
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Sarcosine; Glycine; Magnetic Resonance Spectroscopy; Schizophrenia