- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02237235
Effect of MMFS-202-302 on Cognitive Enhancement in Schizophrenia
Study Overview
Status
Conditions
Intervention / 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University Psychiatric Clinical Research Program
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
Two tablets by mouth in the morning, and two tablets by mouth in the evening, daily for 9 weeks.
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Experimental: MMFS-202 -302
MMFS-202: evening dose MMFS-302: morning dose |
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 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Matrics Consensus Cognitive Battery (MCCB)
Time Frame: Baseline to Day 63
|
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)
Time Frame: Day 63
|
To support the primary endpoint of working memory, the CGI-C will demonstrate clinically relevant improvement of global function.
|
Day 63
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) total score
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) speed of processing domain subscale score
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) attention/vigilance domain subscale score
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) verbal learning domain subscale score
Time Frame: Baseline to Days 42 and 63
|
Baseline to Days 42 and 63
|
|
Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) visual learning domain subscale score
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) reasoning and problem solving domain subscale score
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in cognition measured by the MATRICS Consensus Cognitive Battery (MCCB) social cognition domain subscale score
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in cognition measured by the FAS Phonemic Fluency test
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in cognition measured by the Brown-Peterson's Auditory Consonant Trigrams test
Time Frame: Baseline through Day 63
|
Baseline through Day 63
|
|
Change from Baseline in cognitive outcomes among subgroups of subjects with deficits in the respective cognitive domain
Time Frame: Baseline to Day 63
|
Cognitive outcomes will be reanalyzed, restricted to the subgroup of subjects whose baseline score is at or below median for healthy age-matched norms (T-score of 50 or below) for the respective cognitive outcome of interest.
Analogous analyses will be carried out using more conservative cutoffs of one half and one standard deviation below median (T-score of 45 and 40 or below).
|
Baseline to Day 63
|
Change from Baseline in cognition measured by the Wisconsin Card Sorting Test
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in working memory composite score
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in Negative symptoms measured by the Brief Negative Symptom Scale (BNSS)
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in Negative symptoms measured by the Positive and Negative Syndrome Scale (PANSS) negative symptom subscale
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in Negative symptoms measured by the Calgary Depression Scale for Schizophrenia (CDSS)
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline in Positive symptoms measured by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale
Time Frame: Baseline to Days 42 and 63
|
Baseline to Days 42 and 63
|
|
Overall clinical global impression of severity improvement measured by the change from Baseline of Clinical Global Impressions Scale assessment of severity (CGI-S)
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
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Change from Baseline in brain structure and function
Time Frame: Baseline to Day 63
|
Magnetic Resonance Imaging (MRI) measures of brain structure; resting state functional connectivity; and activation patterns during performance of a working memory paradigm, and of brain reward networks during affective/neutral image appraisal and reward/loss anticipation and outcome (regions of interest: OMPFC, ACC, NAc, VTA).
|
Baseline to Day 63
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Change from Baseline neural activity and connectivity during learning and memory recollection measured by EEG
Time Frame: Baseline to Day 63
|
Baseline to Day 63
|
|
Change from Baseline of red blood cell magnesium levels in relation to efficacy outcome measures
Time Frame: Baseline to Day 63
|
Red blood cell magnesium level will be evaluated as a putative surrogate biomarker of target engagement, as a predictor of efficacy.
|
Baseline to Day 63
|
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: Baseline through Day 63, or Early Termination
|
To evaluate safety and tolerability of MMFS-202-302 in patients with schizophrenia or schizoaffective disorder maintained on a stable dose of an atypical antipsychotic, each grade of adverse event will be evaluated individually, as well as the total number of all grades of adverse events
|
Baseline through Day 63, or Early Termination
|
Responder analyses
Time Frame: Baseline to Day 63
|
The number of subjects achieving a cutoff of improving at least one half of a standard deviation (T-score change > 5) on the working memory subscale of the MCCB will be compared between the MMFS-202-302 and Placebo groups.
Analogous responder analyses will be carried out for other efficacy outcomes.
|
Baseline to Day 63
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- STU00098144
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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