Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
Schizophrenia, Schizoaffective disorder, Cognition, Magnesium, Imaging, Negative symptoms
Brief summary
The goals of this study are to study MMFS-202-302 in a double blind, randomized, placebo-controlled 9-week study of its effect on ameliorating cognitive deficits in 60 patients with schizophrenia or schizoaffective disorder with stable levels of positive symptoms. Secondary end points will include changes in positive and negative symptoms. One dose of MMFS-202-302 will be studied and compared with placebo as adjunctive treatment to atypical antipsychotic drug treatment.
Detailed description
One of the symptoms of schizophrenia is a problem with specific domains of cognition, even when the positive symptoms have been treated. The primary goal of this study is to determine the effectiveness of 9 weeks of supplementation with MMFS-202-302 as augmentation of atypical antipsychotic medication, to improve a critical specific domain of cognitive function, i.e., working memory, in patients with schizophrenia or schizoaffective disorder. To support this primary goal, global function will be assessed with the Clinical Global Impression assessment of change. The investigators will also examine the effect of MMFS-202-302 on other domains of cognition (e.g. attention, executive function, declarative memory, etc.); negative symptoms of schizophrenia; positive symptoms of schizophrenia; MRI measures of brain structure, resting state functional connectivity, and function during evaluation of emotional/unemotional and rewarding/aversive images and anticipation and receipt of reward and punishment, and working memory; and EEG measurement of network interactivity during learning and memory recollection.
Interventions
DRUGMMFS-202-302
Active ingredient: L-Threonic acid Magnesium salt. 1 g (2 pills) by mouth once daily in the evening for 9 weeks Drug: MMFS-302 Active ingredient: L-Threonic Acid Magnesium Salt 1 g (2 pills) by mouth once daily in the morning for 9 weeks
DRUGPlacebo
Two tablets by mouth in the morning, and two tablets by mouth in the evening, daily for 9 weeks.
Sponsors
Neurocentria, Inc.
Brain & Behavior Research Foundation
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. All patients must be capable of giving written informed consent. 2. Male or female subjects of any race; between 18 to 60 years of age, inclusive. 3. No hospitalization other than for evaluation in the past four months 4. Resides in a stable living situation, according to the investigator's judgment. 5. Diagnosis of schizophrenia or schizoaffective disorder of at least one-year duration, as established by the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID-I), and verified with medical records and/or confirmation of diagnosis by the treating clinician. The illness is in a nonacute phase as determined by the subject's primary treating clinician 6. Current psychotropic drug treatment consists of monotherapy with an atypical antipsychotic drug. 7. No more than a mild level of extrapyramidal symptoms (EPS) as determined by the Simpson Angus Scale (SAS) total score: ≤ 6 8. Not taking anticholinergic medication for EPS 9. No evidence of tardive dyskinesia 10. Subjects healthy enough to complete a 9-week clinical trial 11. Women of childbearing potential must have a negative pregnancy test at screening and baseline, and agree to use adequate protection (i.e. double barrier method) for birth control. 12. Able to complete cognition assessments in English 13. General intellectual abilities falling broadly within the average estimated intelligence quotient (IQ) \> 80, as measured by the Wide Range Achievement Test - 4th Edition (WRAT-IV).
Exclusion criteria
1. Failure to perform screening or baseline examinations 2. Hospitalization within 8 weeks before screening, or change of antipsychotic medication or dose within 2 months prior to screening 3. Subjects who have participated in another clinical trial with an experimental medication within the past 2 months. 4. Patient has had cognitive battery similar to those used in this study within the last 12 months 5. Subjects with other Diagnostic and Statistical Manual (DSM-V) Axis I or Axis II primary diagnoses 6. Diagnosis of alcohol or substance abuse or dependence within the past 3 months, 7. Significant suicide risk as determined by the Columbia Suicide Severity Rating Scale (C-SSRS) 8. Subjects who plan to begin a new course of cognitive remediation therapy, or have been receiving cognitive remediation therapy for less than one year. . 9. History of myocardial infarction, unstable angina, uncontrolled hypotension or hypertension within 3 months before screening. 10. Clinically significant abnormality on screening ECG 11. Alanine transaminase (ALT) or aspartate transaminase (AST) \> 2.5 times the upper limit of normal (ULN) 12. History of stroke, brain tumor, head trauma with loss of consciousness, or other clinically significant neurological condition within 12 months before screening 13. Subjects with other uncontrolled medical conditions, in the opinion of the investigator 14. Polypharmacy with two or more antipsychotic drugs or mood stabilizers 15. Use of benzodiazepines 16. Individuals with kidney dysfunction will not be enrolled, as dysfunctional kidneys may have difficulty clearing the magnesium from the body 17. Individuals who are currently taking magnesium supplements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MATRICS Consensus Cognitive Battery (MCCB) | Baseline to Day 63 | Change from Baseline in MATRICS Consensus Cognitive Battery (MCCB) working memory domain. The MCCB measures cognitive function. The MCCB provides an overall composite score, expressed as a T-score, with a mean of 50 and a standard deviation of 10 The MCCB does not have minimum and maximum scores due to the use of T scores. A typical score will fall within a range of 40-60. Scores below 40 indicate impaired cognitive functioning, while scores above 60 suggest above-average cognitive abilities. The MCCB is often used in clinical research to assess cognitive deficits in individuals with psychiatric disorders, and the T-score scale is used to track cognitive changes over time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Clinical Global Impression of Severity Improvement Measured by the Clinical Global Impressions Scale Assessment of Change (CGI-C) | Day 63 | To support the primary endpoint of working memory, the Clinical Global Impression Change (CGI-C) will demonstrate the clinically relevant improvement of global function. Minimum is 1 and Maximum is 6. Higher scores means worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MMFS-202 -302 MMFS-202: evening dose
MMFS-302: morning dose
MMFS-202-302: Active ingredient: L-Threonic acid Magnesium salt.
1 g (2 pills) by mouth once daily in the evening for 9 weeks
Drug: MMFS-302 Active ingredient: L-Threonic Acid Magnesium Salt
1 g (2 pills) by mouth once daily in the morning for 9 weeks | 30 |
| Placebo Placebo
Placebo: Two tablets by mouth in the morning, and two tablets by mouth in the evening, daily for 9 weeks. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Total | Placebo | MMFS-202 -302 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants | 30 Participants | 30 Participants |
| Matrics Consensus Cognitive Battery (MCCB) | 32.8 units on a scale STANDARD_DEVIATION 12.6 | 30.8 units on a scale STANDARD_DEVIATION 12.6 | 34.8 units on a scale STANDARD_DEVIATION 12.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 16 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 11 Participants | 12 Participants |
| Sex: Female, Male Female | 27 Participants | 15 Participants | 12 Participants |
| Sex: Female, Male Male | 33 Participants | 15 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 27 / 30 | 28 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
MATRICS Consensus Cognitive Battery (MCCB)
Change from Baseline in MATRICS Consensus Cognitive Battery (MCCB) working memory domain. The MCCB measures cognitive function. The MCCB provides an overall composite score, expressed as a T-score, with a mean of 50 and a standard deviation of 10 The MCCB does not have minimum and maximum scores due to the use of T scores. A typical score will fall within a range of 40-60. Scores below 40 indicate impaired cognitive functioning, while scores above 60 suggest above-average cognitive abilities. The MCCB is often used in clinical research to assess cognitive deficits in individuals with psychiatric disorders, and the T-score scale is used to track cognitive changes over time.
Time frame: Baseline to Day 63
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MMFS-202 -302 | MATRICS Consensus Cognitive Battery (MCCB) | 41.8 units on a scale | Standard Deviation 9.64 |
| Placebo | MATRICS Consensus Cognitive Battery (MCCB) | 39.67 units on a scale | Standard Deviation 12.86 |
Secondary
Overall Clinical Global Impression of Severity Improvement Measured by the Clinical Global Impressions Scale Assessment of Change (CGI-C)
To support the primary endpoint of working memory, the Clinical Global Impression Change (CGI-C) will demonstrate the clinically relevant improvement of global function. Minimum is 1 and Maximum is 6. Higher scores means worse outcome.
Time frame: Day 63
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MMFS-202 -302 | Overall Clinical Global Impression of Severity Improvement Measured by the Clinical Global Impressions Scale Assessment of Change (CGI-C) | 3.37 score on a scale | Standard Deviation 1.07 |
| Placebo | Overall Clinical Global Impression of Severity Improvement Measured by the Clinical Global Impressions Scale Assessment of Change (CGI-C) | 3.00 score on a scale | Standard Deviation 0.95 |