Glycine vs Placebo for the Schizophrenia Prodrome

Glycine is a natural amino acid neurotransmitter that acts as a co-agonist at NMDA receptors in brain. We hypothesize that symptoms of the schizophrenia prodrome will improve with glycine to a greater degree than with placebo.

Study Overview

• Status: Completed
• Conditions: Schizophrenia Prodrome
• Intervention / Treatment: Drug: Placebo; Drug: Glycine

Detailed Description

A pilot clinical trial comparing glycine to placebo in patients with the schizophrenia prodrome.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • PRIME Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• meet SIPS criteria for schizophrenia prodrome

Exclusion Criteria:

• history of psychosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glycine; Glycine dosing was fixed at an initial dose of 0.2 g/kg q.h.s for 3 days, then 0.2 g/kg b.i.d. for 4 days, then 0.2 g/kg in the a.m. and 0.4 g/kg in the p.m. for 4 days, and finally 0.4 g/kg b.i.d. Subjects weighing > 100 kg were limited to a total daily dose of 80 g daily. Glycine was dispensed under IND 33,515 (DCJ).	Drug: Glycine; Glycine 0.4 g/kg bid
Placebo Comparator: Placebo Group; Placebo was dispensed as a proprietary formulations developed by Glytech, Inc, consisting of microencapsulated sucrose. Recommended administration of the sprinkles was to spoon them onto pudding or applesauce and swallow them with minimal chewing. Since earlier product testing by Glytech revealed that a few individuals did not like the somewhat granular texture of the sprinkles, subjects could switch to a second Glytech placebo formulation, consisting of proprietary pre-flavored sugar powders to be dissolved in 8 ounces of water.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scale of Prodromal Symptoms Total Score	Scale Of Prodromal Symptoms (SOPS) is a 19-item instrument. The SOPS is comprised of symptoms that are classified as falling into four pathology domains: positive, negative, disorganized and general. The scales identify and measure five attenuated positive psychotic symptoms, six negative symptoms, four disorganization symptoms and four general symptoms. These seven-point scales cover severity variance in the subpsychotic or attenuated range. Each item is scaled 0-6, with 0-2 being the normal range, 3-5 being the risk syndrome range, and 6 being severe and psychotic for the positive symptoms and very severe for the other symptoms. The higher the score, the more symptoms an individual has and is therefore negative in its interpretation. The severity of the prodromal state is judged according to the sum of the ratings from each of the SOPS items and can range from 0 to 114. Actual SOPS total scores in this study ranged from 23 to 59 across subjects at baseline.	Baseline
Change in Scale of Prodromal Symptoms Total Score	Scale Of Prodromal Symptoms (SOPS) is a 19-item instrument. The SOPS is comprised of symptoms that are classified as falling into four pathology domains: positive, negative, disorganized and general. The scales identify and measure five attenuated positive psychotic symptoms, six negative symptoms, four disorganization symptoms and four general symptoms. These seven-point scales cover severity variance in the subpsychotic or attenuated range. Each item is scaled 0-6, with 0-2 being the normal range, 3-5 being the risk syndrome range, and 6 being severe and psychotic for the positive symptoms and very severe for the other symptoms. The higher the score, the more symptoms an individual has and is therefore negative in its interpretation. The severity of the prodromal state is judged according to the sum of the ratings from each of the SOPS items and can range from 0 to 114. Actual SOPS total scores in this study ranged from 23 to 59 across subjects at baseline.	Change from Baseline at 8 Weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Alliance for Research on Schizophrenia and Depression; Glytech, Inc
• Investigators: Principal Investigator: Scott W Woods, MD, Yale School of Medicine

Publications and helpful links

General Publications

• Woods SW, Walsh BC, Hawkins KA, Miller TJ, Saksa JR, D'Souza DC, Pearlson GD, Javitt DC, McGlashan TH, Krystal JH. Glycine treatment of the risk syndrome for psychosis: report of two pilot studies. Eur Neuropsychopharmacol. 2013 Aug;23(8):931-40. doi: 10.1016/j.euroneuro.2012.09.008. Epub 2012 Oct 22.

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: February 10, 2006
• First Submitted That Met QC Criteria: February 10, 2006
• First Posted (Estimate): February 13, 2006

Study Record Updates

• Last Update Posted (Actual): April 2, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: schizophrenia prodrome
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Glycine Agents; Glycine
• Other Study ID Numbers: 0502027440

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No