Clinical trial NCT02237235: Effect of MMFS-202-302 on Cognitive Enhancement in Schizophrenia
Official title: Effect of MMFS-202-302 on Cognitive Enhancement in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Schizoaffective Disorder
Keywords: Schizophrenia
Schizoaffective disorder
Cognition
Magnesium
Imaging
Negative symptoms
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Neurocentria, Inc.
name: Brain & Behavior Research Foundation
First posted: 2014-09-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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

Primary outcomes:
measure: Matrics Consensus Cognitive Battery (MCCB)
timeFrame: Baseline to Day 63
Secondary outcomes:
measure: Overall clinical global impression of severity improvement measured by the Clinical Global Impressions Scale assessment of change (CGI-C)
timeFrame: Day 63
Other outcomes:
measure: Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) total score
timeFrame: Baseline to Day 63
measure: Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) speed of processing domain subscale score
timeFrame: Baseline to Day 63
measure: Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) attention/vigilance domain subscale score
timeFrame: Baseline to Day 63
measure: Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) verbal learning domain subscale score
timeFrame: Baseline to Days 42 and 63
measure: Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) visual learning domain subscale score
timeFrame: Baseline to Day 63
measure: Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) reasoning and problem solving domain subscale score
timeFrame: Baseline to Day 63
measure: Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) social cognition domain subscale score
timeFrame: Baseline to Day 63
measure: Change from Baseline in cognition measured by the FAS Phonemic Fluency test
timeFrame: Baseline to Day 63
measure: Change from Baseline in cognition measured by the Brown-Peterson's Auditory Consonant Trigrams test
timeFrame: Baseline through Day 63
measure: Change from Baseline in cognitive outcomes among subgroups of subjects with deficits in the respective cognitive domain
timeFrame: Baseline to Day 63
measure: Change from Baseline in cognition measured by the Wisconsin Card Sorting Test
timeFrame: Baseline to Day 63
measure: Change from Baseline in working memory composite score
timeFrame: Baseline to Day 63
measure: Change from Baseline in Negative symptoms measured by the Brief Negative Symptom Scale (BNSS)
timeFrame: Baseline to Day 63
measure: Change from Baseline in Negative symptoms measured by the Positive and Negative Syndrome Scale (PANSS) negative symptom subscale
timeFrame: Baseline to Day 63
measure: Change from Baseline in Negative symptoms measured by the Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: Baseline to Day 63
measure: Change from Baseline in Positive symptoms measured by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale
timeFrame: Baseline to Days 42 and 63
measure: Overall clinical global impression of severity improvement measured by the change from Baseline of Clinical Global Impressions Scale assessment of severity (CGI-S)
timeFrame: Baseline to Day 63
measure: Change from Baseline in brain structure and function
timeFrame: Baseline to Day 63
measure: Change from Baseline neural activity and connectivity during learning and memory recollection measured by EEG
timeFrame: Baseline to Day 63
measure: Change from Baseline of red blood cell magnesium levels in relation to efficacy outcome measures
timeFrame: Baseline to Day 63
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Baseline through Day 63, or Early Termination
measure: Responder analyses
timeFrame: Baseline to Day 63
Locations:
city: Chicago
country: United States
facility: Northwestern University Psychiatric Clinical Research Program
state: Illinois
Study officials:
affiliation: Northwestern University
name: Herbert Y Meltzer, MD
role: PRINCIPAL_INVESTIGATOR
References: