Glycine vs Placebo for the Schizophrenia Prodrome
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
A pilot clinical trial comparing glycine to placebo in patients with the schizophrenia prodrome.
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
- meet SIPS criteria for schizophrenia prodrome
Exclusion Criteria:
- history of psychosis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | PRIME Clinic | New Haven | Connecticut | United States | 06519 |
Sponsors and Collaborators
- Yale University
- Glytech, Inc
- National Alliance for Research on Schizophrenia and Depression
Investigators
- Principal Investigator: Scott W Woods, MD, Yale School of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0502027440
Study Results
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 Detail | 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. |
| Arm/Group Title | Glycine | Placebo Group |
|---|---|---|
| Arm/Group Description | Glycine dosing group. | Glycine and placebo dosing group. |
| Period Title: Overall Study | ||
| STARTED | 4 | 4 |
| COMPLETED | 3 | 3 |
| NOT COMPLETED | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | Glycine | Placebo Group | Total |
|---|---|---|---|
| Arm/Group Description | 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 | 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 | Total of all reporting groups |
| Overall Participants | 4 | 4 | 8 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
15.3
(0.5)
|
16.5
(2.4)
|
15.9
(1.8)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1
25%
|
1
25%
|
2
25%
|
| Male |
3
75%
|
3
75%
|
6
75%
|
Outcome Measures
| Title | Scale of Prodromal Symptoms Total Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Glycine | Placebo Group |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 4 | 4 |
| Mean (Standard Deviation) [units on a scale] |
37.8
(15.3)
|
37.5
(10.0)
|
| Title | Change in Scale of Prodromal Symptoms Total Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Glycine | Placebo Group |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 4 | 4 |
| Mean (Standard Deviation) [units on a scale] |
-5.8
(8.1)
|
4.5
(9.7)
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Glycine | Placebo Group | ||
| Arm/Group Description | 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 | 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 | ||
All Cause Mortality |
||||
| Glycine | Placebo Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Glycine | Placebo Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | 0/4 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Glycine | Placebo Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/4 (25%) | 4/4 (100%) | ||
| Gastrointestinal disorders | ||||
| Stomach Discomfort | 0/4 (0%) | 0 | 1/4 (25%) | 1 |
| General disorders | ||||
| Disturbed Sleep | 0/4 (0%) | 0 | 2/4 (50%) | 2 |
| Malaise | 0/4 (0%) | 0 | 1/4 (25%) | 1 |
| Psychiatric disorders | ||||
| Irritability | 0/4 (0%) | 0 | 1/4 (25%) | 1 |
| Sedation | 0/4 (0%) | 0 | 2/4 (50%) | 2 |
| Mentation Impaired | 0/4 (0%) | 0 | 1/4 (25%) | 1 |
| Hallucinations | 0/4 (0%) | 0 | 1/4 (25%) | 1 |
| Reproductive system and breast disorders | ||||
| Orgasm Dysfunction | 1/4 (25%) | 1 | 0/4 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Scott W. Woods, MD |
|---|---|
| Organization | Yale University School of Medicine |
| Phone | 203-974-7038 |
| scott.woods@yale.edu |
- 0502027440