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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Schizoaffective Disorder, Schizophrenia

Intervention / Treatment
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* Drug: MMFS-202-302
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must be capable of giving written informed consent. Male or female subjects of any race; between 18 to 60 years of age, inclusive. No hospitalization other than for evaluation in the past four months Resides in a stable living situation, according to the investigator's judgment. 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 Current psychotropic drug treatment consists of monotherapy with an atypical antipsychotic drug. No more than a mild level of EPS as determined by the Simpson Angus Scale (SAS) total score: ≤ 6 Not taking anticholinergic medication for EPS No evidence of tardive dykinesia Subjects healthy enough to complete a 9-week clinical trial 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. Able to complete cognition assessments in English 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: Failure to perform screening or baseline examinations Hospitalization within 8 weeks before screening, or change of antipsychotic medication or dose within 2 months prior to screening Subjects who have participated in another clinical trial with an experimental medication within the past 2 months. Patient has had cognitive battery similar to those used in this study within the last 12 months Subjects with other DSM-V Axis I or Axis II primary diagnoses Diagnosis of alcohol or substance abuse or dependence within the past 3 months, Significant suicide risk as determined by the Columbia Suicide Severity Rating Scale (C-SSRS) Subjects who plan to begin a new course of cognitive remediation therapy, or have been receiving cognitive remediation therapy for less than one year. . History of myocardial infarction, unstable angina, uncontrolled hypotension or hypertension within 3 months before screening. Clinically significant abnormality on screening ECG Alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5 times the upper limit of normal (ULN) History of stroke, brain tumor, head trauma with loss of consciousness, or other clinically significant neurological condition within 12 months before screening Subjects with other uncontrolled medical conditions, in the opinion of the investigator Polypharmacy with two or more antipsychotic drugs or mood stabilizers Use of benzodiazepines Individuals with kidney dysfunction will not be enrolled, as dysfunctional kidneys may have difficulty clearing the magnesium from the body Individuals who are currently taking magnesium supplements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMFS-202 -302<br>MMFS-202: evening dose MMFS-302: morning dose | Drug: MMFS-202-302<br>* 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<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Two tablets by mouth in the morning, and two tablets by mouth in the evening, daily for 9 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Matrics Consensus Cognitive Battery (MCCB) | Change from Baseline in MATRICS Consensus Cognitive Battery (MCCB) working memory domain. | Baseline to Day 63 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 CGI-C will demonstrate clinically relevant improvement of global function. | Day 63 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Schizoaffective disorder, Cognition, Magnesium, Imaging, Negative symptoms