Study of the Effects of Glycine on Symptoms and Memory in Patients With Schizophrenia

NCT00575848 | Terminated Phase 1

• 1 other identifier: CORRC #1-2007
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this project is to understand whether glycine is helpful for improving some symptoms of schizophrenia such as low motivation, loss of interest, and social isolation. In addition, the investigators want to find out if glycine improves memory. This project involves a three-and-a-half month trial of glycine or placebo. A placebo looks exactly like the study drug, but it contains no active drug. Glycine is a naturally occurring substance that is a part of some of the proteins in your body. Glycine has not been approved by the FDA (Food and Drug Administration) for the treatment of schizophrenia. However, the FDA allows it to be used in research studies. Related Study at McLean Hospital: If you would like to participate in this study of glycine versus placebo at the Freedom Trail Clinic, the investigators will ask you if you would also like to participate in a related study at McLean Hospital. The study at McLean Hospital will look at the effects of glycine and placebo on levels of glycine in the brain. The study will use magnetic resonance spectroscopy to measure brain glycine levels. The magnetic resonance (MR) scanner looks like a large cylinder with a tube running down the center. You will be asked to lie down on your back on a foam-padded table and place your head into a special holder. The table will slide you inside the "hole" of the scanner. Soft foam rubber sponges may be placed on both sides of your head for comfort and to help keep your head from moving. Because the scanner contains a strong magnet, you will be asked to remove all metal objects from your person including, but not limited to: watches, rings, necklaces, bracelets, earrings and other body piercings, belts, loose change, wallet (with credit cards), items of clothing containing magnetic materials (for example, underwire bras, certain types of zippers), and shoes. These items will be secured in a safe place until your scan is completed. You will be able to remain in your street clothes. The investigators will ask you if study staff from McLean Hospital can contact you to tell you more about the study. You may refuse to be contacted by McLean Hospital. However, if you do not participate in the study at McLean, you are not eligible for the study here at the Freedom Trail Clinic.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Schizophrenia; Glycine; Magnetic Resonance Spectroscopy (MRS)

Outcome Measures

Primary Outcomes (1)

• Scale for the Assessment of Negative Symptoms (SANS) total score

  14 weeks

Secondary Outcomes (3)

• Brief Psychiatric Rating Scale (BPRS) positive symptom subscale

  14 weeks

• Performance on the Logical Memory subtest of the Wechsler Memory Scale

  14 weeks

• Correlations between changes in clinical symptoms and changes in brain glycine levels as measured by MRS at McLean Hospital

  14 weeks

Study Arms (2)

1

ACTIVE COMPARATOR

Dietary Supplement: Glycine

2

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

Glycine DIETARY_SUPPLEMENT

Subjects will consume glycine twice daily, once with breakfast and once with dinner. The medication is in liquid form. They will be instructed to refrigerate the liquid until the time that they take it. Subjects start by taking 10g per day for the first 2 days. Starting on the 3rd day, subjects take 0.2g/kg (15g for a 75kg adult) per day, and increase dosage by 0.2g/kg every two days, until they reach 0.8g/kg per day, which they take for the remainder of the 6-week period.

1

Placebo DIETARY_SUPPLEMENT

Subjects will consume placebo twice daily, once with breakfast and once with dinner. The placebo is in liquid form. They will be instructed to refrigerate the liquid until the time that they take it. Subjects start by taking 10g per day for the first 2 days. Starting on the 3rd day, subjects take 0.2g/kg (15g for a 75kg adult) per day, and increase dosage by 0.2g/kg every two days, until they reach 0.8g/kg per day, which they take for the remainder of the 6-week period.

2

Eligibility Criteria

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

You may qualify if:

• Males 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 (any except clozapine or olanzapine) for at least one month, no current active suicidal ideation
• Not treated with investigational medication in the past 30 days
• Competent to provide informed consent

You may not qualify if:

• Diagnosis of dementia, neurodegenerative disease, seizure disorder, current substance abuse or dependence disorders, including alcohol, active within the last 3 months or any Axis I DSM-IV diagnosis other than schizophrenia or schizoaffective disorder
• Serious illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease that is not stabilized such that hospitalization for treatment of that illness is likely within the next four months
• Patients who, in the investigator's opinion, pose a current severe homicide or suicide risk
• History of multiple head injuries with neurological sequelae or a single severe head injury with lasting neurological sequelae
• Uncontrolled hypertension
• Anuretic
• Use of clozapine or olanzapine in the past month
• Subjects who weigh more than 275 lbs
• Subjects who are claustrophobic
• Subjects with a history of electrolyte imbalance
• Subjects who have lost consciousness for 30 minutes or more
• Subjects with lifetime history of stroke
• Subjects with myocardial infarction within the last 6 months
• Those having a pacemaker or a heart arrhythmia
• Source of metal in body incompatible with MRI procedures

Sponsors & Collaborators

• North Suffolk Mental Health Association: lead
• Mclean Hospital: collaborator
• National Alliance for Research on Schizophrenia and Depression: collaborator

Study Sites (2)

Brain Imaging Center, McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Freedom Trail Clinic, Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (12)

• Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry. 1995 Dec;52(12):998-1007. doi: 10.1001/archpsyc.1995.03950240016004.

  PMID: 7492260 BACKGROUND

• Reveley MA, De Belleroche J, Recordati A, Hirsch SR. Increased CSF amino acids and ventricular enlargement in schizophrenia: a preliminary study. Biol Psychiatry. 1987 Apr;22(4):413-20. doi: 10.1016/0006-3223(87)90163-6.

  PMID: 3567257 BACKGROUND

• Kurumaji A, Watanabe A, Kumashiro S, Semba J, Toru M. A postmortem study of glycine and its potential precursors in chronic schizophrenics. Neurochem Int. 1996 Sep;29(3):239-45. doi: 10.1016/0197-0186(96)00013-7.

  PMID: 8885282 BACKGROUND

• Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Silipo G, Lichtenstein M. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry. 1999 Jan;56(1):29-36. doi: 10.1001/archpsyc.56.1.29.

  PMID: 9892253 BACKGROUND

• Evins AE, Fitzgerald SM, Wine L, Rosselli R, Goff DC. Placebo-controlled trial of glycine added to clozapine in schizophrenia. Am J Psychiatry. 2000 May;157(5):826-8. doi: 10.1176/appi.ajp.157.5.826.

  PMID: 10784481 BACKGROUND

• Prescot AP, de B Frederick B, Wang L, Brown J, Jensen JE, Kaufman MJ, Renshaw PF. In vivo detection of brain glycine with echo-time-averaged (1)H magnetic resonance spectroscopy at 4.0 T. Magn Reson Med. 2006 Mar;55(3):681-6. doi: 10.1002/mrm.20807.

  PMID: 16453318 BACKGROUND

• Andreasen NC. The Scale for the Assessment of Negative Symptoms (SANS): conceptual and theoretical foundations. Br J Psychiatry Suppl. 1989 Nov;(7):49-58. No abstract available.

  PMID: 2695141 BACKGROUND

• Overall, J. E. & Gorham, D. R. The brief psychiatric rating scale (BPRS). Psychol Reports 10, 799-812 (1962).

  BACKGROUND

• Wechsler, D. Weschsler Adult Intelligence Scale-III (The Psychological Corporation, San Antonio, TX, 1997).

  BACKGROUND

• Farber NB, Newcomer JW, Olney JW. Glycine agonists: what can they teach us about schizophrenia? Arch Gen Psychiatry. 1999 Jan;56(1):13-7. doi: 10.1001/archpsyc.56.1.13. No abstract available.

  PMID: 9892251 BACKGROUND

• Potkin SG, Jin Y, Bunney BG, Costa J, Gulasekaram B. Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. Am J Psychiatry. 1999 Jan;156(1):145-7. doi: 10.1176/ajp.156.1.145.

  PMID: 9892314 BACKGROUND

• Shoham S, Javitt DC, Heresco-Levy U. Chronic high-dose glycine nutrition: effects on rat brain cell morphology. Biol Psychiatry. 2001 May 15;49(10):876-85. doi: 10.1016/s0006-3223(00)01046-5.

  PMID: 11343684 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Glycine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• A. Eden Evins, M.D., M.P.H.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Andrew Prescot, Ph.D.

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 14, 2007
• First Posted: December 18, 2007
• Study Start: December 1, 2007
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: November 26, 2009

Record last verified: 2009-11

Locations

US (2)