Acute Glycine Pharmacodynamic Study

NCT01610011 | Completed Results

• 1 other identifier: 2010P001576
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to use proton magnetic resonance spectroscopy (MRS) at 4 Tesla to measure brain glycine levels noninvasively at baseline and for 2 hours after a single oral dose of a concentrated glycine-containing beverage, and to compare MRS glycine measurements to glycine blood levels in samples obtained after each MRS spectrum. The investigators hypothesize that they will observe a high correlation between the magnitude increases in brain and plasma glycine levels over this time frame. The investigators also hypothesize that we will observe large intersubject variability in glycine uptake rates into brain and blood. The investigators also hypothesize that subjects with a glycine decarboxylase (GLDC) mutation (triplication) will have lower baseline plasma and brain glycine levels and will experience smaller brain and plasma glycine increases after glycine consumption than controls or family members without the GLDC mutation.

Conditions

Schizophrenia; Psychotic Disorders

Keywords

Schizophrenia; Psychotic Disorders; N-methyl-D-aspartate receptor; Glycine augmentation; Glycine; Glycine Pharmacodynamics; Glycine Bioavailability; Magnetic Resonance Spectroscopy; Glycine Decarboxylase; Glycine Decarboxylase Mutation

Outcome Measures

Primary Outcomes (1)

• Brain Glycine Increments After Oral Glycine Administration Measured With MRS as Glycine/Total Creatine, Normalized to the Glycine Dose Administered (g/kg).

  Brain and plasma glycine levels are measured with proton magnetic resonance spectroscopy at 4T and analytically, respectively. Because glycine doses were limited to 30 g to avoid nausea and vomiting, some subjects with higher weights were administered lower doses per body weight of glycine (g/kg). Therefore, we corrected MRS data by the actual glycine dose administered (g/kg) to account for dosing differences.

  For up to 2 hours

Study Arms (1)

Glycine administration

EXPERIMENTAL

Glycine will be administered once orally to all subjects to determine brain and plasma pharmacodynamics.

Dietary Supplement: Glycine administration

Interventions

Glycine administration DIETARY_SUPPLEMENT

Glycine will be administered once as a 250 cc lemon-flavored beverage based on each subject's body weight. The drink concentration will be 0.4 g/kg glycine (not to exceed 30 grams). Subjects will have 10 minutes to consume the beverage.

Also known as: Aminoacetic Acid, Aminoethanoic Acid

Glycine administration

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Adult males
• Members of a family known to the research team with some members possessing a GLDC genetic mutation

You may not qualify if:

• Contraindications to magnetic resonance scanning including metallic surgical implants or claustrophobia
• History of head injury with loss of consciousness \> 5 minutes
• Brain structural abnormalities identified on MRI scan
• Known sensitivity or allergy to glycine
• History of taking glycine or other dietary supplements
• Healthy controls: history of psychiatric or substance use disorders; individuals taking prescription medications
• Pregnancy

Sponsors & Collaborators

• Mclean Hospital: lead
• Brain & Behavior Research Foundation: collaborator

Study Sites (1)

McLean Imaging Center, McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Related Publications (7)

• 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

• Bergeron R, Meyer TM, Coyle JT, Greene RW. Modulation of N-methyl-D-aspartate receptor function by glycine transport. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15730-4. doi: 10.1073/pnas.95.26.15730.

  PMID: 9861038 BACKGROUND

• Silk DB, Kumar PJ, Perrett D, Clark ML, Dawson AM. Amino acid and peptide absorption in patients with coeliac disease and dermatitis herpetiformis. Gut. 1974 Jan;15(1):1-8. doi: 10.1136/gut.15.1.1.

  PMID: 4820629 BACKGROUND

• D'Souza DC, Gil R, Cassello K, Morrissey K, Abi-Saab D, White J, Sturwold R, Bennett A, Karper LP, Zuzarte E, Charney DS, Krystal JH. IV glycine and oral D-cycloserine effects on plasma and CSF amino acids in healthy humans. Biol Psychiatry. 2000 Mar 1;47(5):450-62. doi: 10.1016/s0006-3223(99)00133-x.

  PMID: 10704956 BACKGROUND

• Buchanan RW, Javitt DC, Marder SR, Schooler NR, Gold JM, McMahon RP, Heresco-Levy U, Carpenter WT. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry. 2007 Oct;164(10):1593-602. doi: 10.1176/appi.ajp.2007.06081358.

  PMID: 17898352 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

• Kaufman MJ, Prescot AP, Ongur D, Evins AE, Barros TL, Medeiros CL, Covell J, Wang L, Fava M, Renshaw PF. Oral glycine administration increases brain glycine/creatine ratios in men: a proton magnetic resonance spectroscopy study. Psychiatry Res. 2009 Aug 30;173(2):143-9. doi: 10.1016/j.pscychresns.2009.03.004. Epub 2009 Jun 24.

  PMID: 19556112 BACKGROUND

Related Links

• Brain and Behavior Research Foundation - Awarding NARSAD Grants

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Hyperglycinemia, Nonketotic

Interventions

Glycine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

This trial was limited by small sample sizes, especially in the GLDC mutation group, since this is a rare genetic mutation.

Results Point of Contact

• Title: Marc J. Kaufman, Ph.D., Principal Investigator
• Organization: McLean Hospital

kaufman@mclean.harvard.edu

617-855-3469

Study Officials

• Marc J. Kaufman, Ph.D.

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Translational Imaging Laboratory

Study Record Dates

• First Submitted: May 28, 2012
• First Posted: June 1, 2012
• Study Start: July 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: October 27, 2015
• Results First Posted: October 27, 2015

Record last verified: 2015-09

Locations

US (1)