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

Primary Purpose

Schizophrenia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Sarcosine
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Sarcosine, Glycine, Magnetic Resonance Spectroscopy, Schizophrenia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • McLean Hospital, Brain Imaging Center
  • MGH Center for Addiction Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Sarcosine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Increases in brain glycine concentration as measured by magnetic resonance spectroscopy

Secondary Outcome Measures

Full Information

First Posted
October 1, 2007
Last Updated
September 17, 2012
Sponsor
Massachusetts General Hospital
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT00538070
Brief Title
A Study of the Effects of Sarcosine on Symptoms and Brain Glycine Levels in People With Schizophrenia
Acronym
Sarc
Official Title
The Effects of Glycine Transport Inhibition on Brain Glycine Concentration
Study Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Sarcosine, Glycine, Magnetic Resonance Spectroscopy, Schizophrenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Sarcosine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Sarcosine
Other Intervention Name(s)
glycine transport inhibitor
Intervention Description
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.
Primary Outcome Measure Information:
Title
Increases in brain glycine concentration as measured by magnetic resonance spectroscopy
Time Frame
baseline and endpoint

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: 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. EXCLUSION CRITERIA: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A. Eden Evins, M.D., M.P.H.
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marc Kaufman, Ph.D.
Organizational Affiliation
Mclean Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
McLean Hospital, Brain Imaging Center
City
Belmont
State/Province
Massachusetts
ZIP/Postal Code
02478
Country
United States
Facility Name
MGH Center for Addiction Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

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

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