Schizophrenia Prodrome
Conditions
Keywords
schizophrenia prodrome
Brief summary
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.
Detailed description
A pilot clinical trial comparing glycine to placebo in patients with the schizophrenia prodrome.
Interventions
DRUGGlycine
Glycine 0.4 g/kg bid
DRUGPlacebo
Placebo
Sponsors
Glytech, Inc
National Alliance for Research on Schizophrenia and Depression
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* meet SIPS criteria for schizophrenia prodrome
Exclusion criteria
* history of psychosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Scale of Prodromal Symptoms Total Score | Baseline | 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 in Scale of Prodromal Symptoms Total Score | Change from Baseline at 8 Weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled between March 2006 and May 2008. Potential subjects or their families or providers were informed about the symptoms of the risk syndrome for psychosis through a variety of ongoing community education efforts and were invited to call our research clinic if concerned.
Pre-assignment details
Exclusions: 1) past or current DSM IV criteria for any lifetime psychotic disorder, 2) alcohol or drug abuse or dependence in the past three months, 3) use of antipsychotic medication in the previous three months, 4) change in dosage of any antidepressant, anxiolytic, psychostimulant, or mood stabilizer medication within eight weeks.
Participants by arm
| Arm | Count |
|---|---|
| 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 and placebo were dispensed under IND 33,515 (DCJ) as one of two proprietary formulations developed by Glytech, Inc. Dosing was initiated with small microencapsulated beads or sprinkles (80% glycine by weight), with placebo consisting of microencapsulated sucrose. Recommended administration of the sprinkles was to spoon them onto pudding or applesauce and swallow them with minimal chewing.
Glycine: Glycine 0.4 g/kg bid | 4 |
| Placebo Group Glycine and placebo were dispensed under IND 33,515 (DCJ) as one of two proprietary formulations developed by Glytech, Inc. Dosing was initiated with small microencapsulated beads or sprinkles (80% glycine by weight), with placebo 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 formulation, consisting of proprietary pre-flavored glycine or sugar powders to be dissolved in 8 ounces of water.
Placebo: Placebo | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Glycine | Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 15.3 years STANDARD_DEVIATION 0.5 | 16.5 years STANDARD_DEVIATION 2.4 | 15.9 years STANDARD_DEVIATION 1.8 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 4 | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
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.
Time frame: Change from Baseline at 8 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycine | Change in Scale of Prodromal Symptoms Total Score | -5.8 units on a scale | Standard Deviation 8.1 |
| Placebo Group | Change in Scale of Prodromal Symptoms Total Score | 4.5 units on a scale | Standard Deviation 9.7 |
Primary
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.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycine | Scale of Prodromal Symptoms Total Score | 37.8 units on a scale | Standard Deviation 15.3 |
| Placebo Group | Scale of Prodromal Symptoms Total Score | 37.5 units on a scale | Standard Deviation 10 |