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

September 17, 2012 updated by: A. Eden Evins, Massachusetts General Hospital

The Effects of Glycine Transport Inhibition on Brain Glycine Concentration

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Belmont, Massachusetts, United States, 02478
        • McLean Hospital, Brain Imaging Center
      • Boston, Massachusetts, United States, 02114
        • MGH Center for Addiction Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

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

EXCLUSION CRITERIA:

  1. Diagnosis of bipolar disorder, dementia, neurodegenerative disease, or other organic mental disorder.
  2. History of seizure disorder or CNS tumor.
  3. Liver function tests elevated over twice normal.
  4. Bulimia, or major depressive disorder within the last 6 months.
  5. 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.
  6. Use of investigational medication within 30 days of enrollment.
  7. Use of clozapine.
  8. Substance use disorder other than nicotine or caffeine in the last 6 months (by self report and salivary drug and alcohol screen).
  9. Posing a current risk of homicide or suicide.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
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
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 Names:
  • glycine transport inhibitor
Experimental: Sarcosine
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
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 Names:
  • glycine transport inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Increases in brain glycine concentration as measured by magnetic resonance spectroscopy
Time Frame: baseline and endpoint
baseline and endpoint

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: A. Eden Evins, M.D., M.P.H., Massachusetts General Hospital
  • Principal Investigator: Marc Kaufman, Ph.D., McLean Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

July 1, 2012

Study Completion (Actual)

July 1, 2012

Study Registration Dates

First Submitted

October 1, 2007

First Submitted That Met QC Criteria

October 1, 2007

First Posted (Estimate)

October 2, 2007

Study Record Updates

Last Update Posted (Estimate)

September 18, 2012

Last Update Submitted That Met QC Criteria

September 17, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1R01DA022276-01 (U.S. NIH Grant/Contract)
  • DPMC (Other Identifier: NIDA)
  • 1R01DA022276 (U.S. NIH Grant/Contract)
  • #2007-P-000416/1
  • R01DA022276 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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