Effect of MMFS-202-302 on Cognitive Enhancement in Schizophrenia

• Neuroimaging [ Time Frame: One year ]
  To determine the effect of MMFS-202-302 as augmentation of atypical antipsychotic medication on both the behavioral performance and activation patterns in schizophrenia patients during a WM neuroimaging paradigm. Specifically, investigation in whether improvement from baseline task performance occurs for the MMFS-202-302 + APD group, and if this improvement is associated with increases in WM-related brain region activation (DLPFC & PPC).
• EEG [ Time Frame: One year ]
  To evaluate the effect of MMFS-202-302 on activity and connectivity in the brain using EEG methods

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 MMFS-202-302 as augmentation of atypical antipsychotic medication, to improve specific domains of cognitive function, e.g. attention, executive function, declarative memory, etc in patients with schizophrenia or schizoaffective disorder.

The investigators will also examine the effect of MMFS-202-302 on negative symptoms of schizophrenia, positive symptoms of schizophrenia, and working memory as measured by a neuroimaging paradigm.

• Schizophrenia
• Schizoaffective Disorder

• Drug: MMFS-202-302

  Active ingredient: L-Threonic acid Magnesium salt.

  Inactive ingredients: polyvinyl pyrolidone, microcrystalline cellulose, silicon dioxide, talc, and magnesium stearate.

• Drug: Placebo
  Inactive ingredients for placebo: talc, magnesium stearate, povidone K-90, colloidal silicon dioxide, microcrystalline cellulose, sodium carboxymethylcellulose, carbopol 974P, starcap 1500.

• Experimental: MMFS-202-302

  MMFS-202: 1 g/per day (2 pills)

  MMFS-302: 2 g/day (2 pills)

  Intervention: Drug: MMFS-202-302
• Placebo Comparator: Placebo
  Placebo 4 pills/day
  Intervention: Drug: Placebo

Inclusion Criteria:

1. All patients must be capable of giving written informed consent.
2. Male or female subjects of any race; between 18 to 55 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 SCID-I, and verified with medical records and/or confirmation of diagnosis by 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 EPS as determined by the Simpson Angus Scale (SAS) total score: ≤ 6
8. Not taking anticholinergic medication for EPS
9. No evidence of tardive dykinesia
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 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 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

• Neurocentria, Inc.
• Brain & Behavior Research Foundation