Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 4 for:    neurocentria

Efficacy and Safety of MMFS in Early AD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03531684
Recruitment Status : Completed
First Posted : May 22, 2018
Last Update Posted : September 9, 2020
Sponsor:
Collaborator:
Ohio State University
Information provided by (Responsible Party):
Neurocentria, Inc.

Brief Summary:
This study is designed to evaluate the safety and efficacy of MMFS for improving cognition and global function in patients with probable Early Alzheimer's disease.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Dietary Supplement: MMFS-205-SR Dietary Supplement: Placebo Phase 2

Detailed Description:
This is a phase 2 study in patients with probable Early Alzheimer's disease (AD). Early AD includes Stage 3 AD patients (MCI due to AD) and Stage 4 AD patients (mild AD). The study is a randomized, double-blind, placebo controlled, parallel group design, in which participants (up to 6 per arm; 12 total) will receive oral placebo or MMFS twice daily for 24 weeks. Randomized patients and their informants (required) will complete 3 assessments total: at baseline (prior to taking any study tablets), week 12, and week 24 visits. At each of the three visits, participants will complete cognitive and behavioral measures and clinical interviews, a blood sample will be collected for safety and biomarkers related to Alzheimer's disease, and the informant will complete an interview concerning the patient's cognition, mood, and function. A range of safety and tolerability assessments will also be performed (including vital signs, laboratory tests, and ECGs). Participants will be contacted by phone between clinical assessments for monitoring.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Clinical Trial to Test the Efficacy and Safety of MMFS-205 in Early Alzheimer's Disease Patients
Actual Study Start Date : March 20, 2018
Actual Primary Completion Date : April 22, 2020
Actual Study Completion Date : April 22, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MMFS-205-SR
Oral MMFS-205-SR twice daily (2,000, 3,000, or 4,000 mg/day total, depending on lean body mass and response to initial dose at Week 12) for 24 weeks
Dietary Supplement: MMFS-205-SR
Twice daily, oral, 500 mg tablets
Other Name: L-threonic acid magnesium salt, L-TAMS

Placebo Comparator: Placebo
Oral inactive placebo twice daily for 24 weeks
Dietary Supplement: Placebo
Twice daily, oral
Other Name: Inactive sugar pill




Primary Outcome Measures :
  1. Neuropsychological Test Battery (NTB) standardized composite score [ Time Frame: Change from baseline at 24 weeks ]
    Standardized composite score generated from a battery of 4 cognitive tests, including: 1) COWAT - Category Fluency assessment of semantic fluency; 2) WAIS-IV Coding (Digit Symbol Substitution Test; DSST) assesment of attention speed of processing, mental flexibility and executive function; 3) Free and Cued Selective Reminding Test Immediate Recall (FCSRT-IR) assessment of episodic visual memory; 4) Wechsler Logical Memory II (Delayed Recall) assessment of narrative memory.

  2. Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) score [ Time Frame: Change from baseline at 24 weeks ]
    Composite measure of cognition and global function. The scores in each domain range from 0-3, referring to impairment with 0 being none, 0.5 being questionable, 1 being mild, 2 being moderate, and 3 being severe.


Secondary Outcome Measures :
  1. Modified Mini-Mental State Examination (mMMSE) total score [ Time Frame: Change from baseline at 12 and 24 weeks ]
    Cognitive test; the mMMSE is scored as the number of correctly completed items, with lower scores indicative of poorer performance and greater cognitive impairment. The score ranges from 0 to 100, with 100 being perfect performance. An mMMSE-derived MMSE score ranging from 0 to 30, with 30 being perfect performance, can also be generated.

  2. Alzheimer's Disease Cooperative Scale-Activities of Daily Living-Mild Cognitive Impairment 24 questions (ADCS-ADL-MCI24) [ Time Frame: Change from baseline at 12 and 24 weeks ]
    Survey assessing daily function; scores range from 0 to 53 for the ADL section and 0 to 16 for the instrumental ADL section, with lower scores demonstrating more functional impairment.

  3. Alzheimer's Disease Cooperative Scale - Clinical Global Impression of Change (ADCS-MCI-CGIC) score [ Time Frame: Change from baseline at 12 and 24 weeks ]
    Clinical assessment of global function. The Clinician's Global Impression of Change Scale (ADCS-MCI-CGIC) is rated on a 7-point scale with the change scale using a range of responses from 1 (very much improved) through 7 (very much worse).

  4. Neuropsychiatric Inventory (NPI) sub score [ Time Frame: Change from baseline at 12 and 24 weeks ]
    Informant interview assessment of patient's neuropsychiatric symptom severity. The score for each domain is defined as frequency times severity and total NPI score is defined as the sum of the individual category scores. Higher scores on NPI indicate a more frequent and/or severe presence of neuropsychiatric behavioral changes. The following domains will be included in the subscore: Depression/Dysphoria, Anxiety, Apathy/Indifference, Irritability/Lability, Agitation/Aggression, and Disinhibition.


Other Outcome Measures:
  1. Physical Activity Scale for the Elderly (PASE) [ Time Frame: Change from baseline at 12 and 24 weeks ]
    The PASE is a short survey designed to assess physical activity specifically in elderly.

  2. Geriatric Depression Scale (GDS) [ Time Frame: Change from baseline at 12 and 24 weeks ]
    The GDS is a self-report measure of depression in older adults. Users respond to 30 questions in a "Yes/No" format. In scoring the GDS, each item is scored 0 or 1 depending upon whether the item is worded positively or negatively. The total score on the scale ranges from 0 to 30.

  3. Brief Smell Identification Test (BSIT) score [ Time Frame: Change from baseline at 12 and 24 weeks ]
    Olfaction assessment. The total olfaction score is defined as the number of odorants correctly identified out of the 12 tested, with higher scores denoting better performance. Identification of fewer than nine odorants is considered abnormal olfactory function.

  4. Neuropsychiatric Inventory (NPI) total score [ Time Frame: Change from baseline at 12 and 24 weeks ]
    Informant interview assessment of patient's neuropsychiatric symptom severity. The score for each domain is defined as frequency times severity and total NPI score is defined as the sum of the individual category scores. Higher scores on NPI indicate a more frequent and/or severe presence of neuropsychiatric behavioral changes.

  5. Neuropsychological Test Battery (NTB) standardized composite score at 12 weeks [ Time Frame: 12 weeks ]
    Standardized composite score generated from a battery of 4 cognitive tests, including: 1) COWAT - Category Fluency assessment of semantic fluency; 2) WAIS-IV Coding (Digit Symbol Substitution Test; DSST) assesment of attention speed of processing, mental flexibility and executive function; 3) Free and Cued Selective Reminding Test Immediate Recall (FCSRT-IR) assessment of episodic visual memory; 4) Wechsler Logical Memory II (Delayed Recall) assessment of narrative memory.

  6. Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) score at 12 weeks [ Time Frame: 12 weeks ]
    Composite measure of cognition and global function. The scores in each domain range from 0-3, referring to impairment with 0 being none, 0.5 being questionable, 1 being mild, 2 being moderate, and 3 being severe.

  7. Responder analyses of Modified Mini-Mental State Examination (mMMSE) [ Time Frame: Change from baseline at 12 and 24 weeks ]
    Cognitive test; the mMMSE is scored as the number of correctly completed items, with lower scores indicative of poorer performance and greater cognitive impairment. The score ranges from 0 to 100, with 100 being perfect performance. Positive responders are subjects who achieve at least a 3-point improvement on mMMSE

  8. Neuropsychological Test Battery cognitive domain analyses [ Time Frame: Change from baseline at 12 and 24 weeks, or change from baseline at 24 weeks, as appropriate ]
    Analysis of individual cognitive tests comprising the Neuropsychological Test Battery (NTB)

  9. Insulin resistance markers [ Time Frame: Change from baseline at 12 and 24 weeks ]
    HbA1c and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR): fasting glucose and insulin



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients meeting all of the following inclusion criteria should be considered for admission to the study:

  1. MMSE ≥ 19
  2. ≥ 55 and ≤ 85 years old at Screening
  3. Meet criteria for at least one of the following Stages of Early Alzheimer's Disease as defined below:

    Stage 3 AD (MCI due to AD)

    1. CDR Global score = 0.5, with

      • 0.5 on memory box score; and
      • 0.5 on at least one of the following functional measures: community affairs, home & hobbies, or personal care
    2. MMSE ≥ 24

    Stage 4 AD (Mild AD):

    1. CDR Global score = 1, with

      • 0.5 on memory box score; and
      • 0.5 on at least one of the following functional measures: community affairs, home & hobbies, or personal care; OR
    2. CDR Global score = 0.5, with

      • 0.5 on memory box score; and
      • 0.5 on at least one of the following functional measures: community affairs, home & hobbies, or personal care; and MMSE 19-23
  4. ≥ 3 on at least one of the following Neuropsychiatric Inventory (NPI) behavioral areas: Agitation/Aggression, Depression/Dysphoria, Anxiety, Apathy/Indifference, Disinhibition, or Irritability/Lability, and total NPI score in these behavioral areas ≥ 6.
  5. Total Body weight (bw) must be ≥50 kg and ≤110 kg and lean body mass (LBM) must be ≤ 85 kg at screening
  6. Must be fluent in English
  7. Must have a friend/family member who frequently spends time with the subject (≥10 hours per week), and is willing to serve as an informant, and accompany the subject to, and participate in, all clinic visits
  8. Completion of at least 10 years of formal education (i.e., possess high school diploma, GED, or equivalent)
  9. Hearing and Vision ability sufficient to complete neurocognitive testing
  10. Be able and willing to collect urine (at home) for 12 hours the day prior to follow up visits (optional for Stage 4 patients).

Exclusion Criteria

Patients meeting any of the following exclusion criteria will not be enrolled in the study:

Exclusions to rule out subjects with cognitive impairment likely due to something other than AD:

  1. Known negative biomarker for brain amyloid pathology as indicated by either amyloid PET or CSF assessment or both
  2. Stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year
  3. Clinically significant psychiatric illness in past 6 months requiring hospitalization
  4. Seizure in the past 3 years
  5. Within 1 year before the screening or between screening and baseline, any of the following: myocardial infarction; moderate or severe congestive heart failure, New York Heart Association class III or IV; hospitalization for, or symptom of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (e.g., significant valvular disease, hypertrophic cardiomyopathy), or hospitalization for arrhythmia; congenital QT prolongation
  6. Subject report of human immunodeficiency virus (HIV) infection
  7. History of evidence of acute or sub-acute micro or macrohemorrhage, greater than 4 microhemorrhages, cortical infarct, or greater than one 1 lunar infarct
  8. Alcohol or substance abuse in past 1 year
  9. Untreated and/or uncontrolled hypothyroidism
  10. Evidence of vascular dementia (Modified Hachinski Ischemia Scale score >5)
  11. History of clinically important carotid or vertebrobasilar stenosis or plaque
  12. Systemic chemotherapy in past 1 year
  13. Diagnosis of Multiple Sclerosis
  14. Unintentional rapid weight loss (>10% body weight within past 12 months)

    Exclusions to rule out subjects with potential issues absorbing or metabolizing MMFS:

  15. Poor kidney function; corrected estimated glomerular filtration rate (eGFRcorr) < 40 mL/min/m2
  16. History of significant gastrointestinal disorder, such as chronic Diarrhea, irritable bowel syndrome, ulcerative colitis, Chron's disease, etc.

    Exclusions to rule out subjects with sleeping problems not related to CNS disorder:

  17. Diagnosed with apnea/hypopnea but not using Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BIPAP). If diagnosed with apnea/hypopnea, subject must maintain use of device throughout study
  18. Untreated nocturia that affects sleep

    Exclusions to rule out subjects with conditions that could affect their safety:

  19. Females of child-bearing potential, as defined as menstruation within past 12 months or not surgically sterile.
  20. Systolic blood pressure > 150 mm Hg
  21. An affirmative response on the C-SSRS, indicating suicidal ideation with intent, with or without a plan or method, or suicidal behavior, in the past 6 months.

    Exclusions to rule out subjects with conditions that could inhibit or confound the effects of MMFS or the ability of the subject to complete the study:

  22. Serious or unstable clinically important systemic illness or disease that, in the judgment of the investigator, is likely to affect cognitive assessment, deteriorate, or affect the participant's safety or ability to complete the study, including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, or hematologic disorders
  23. Currently living in an institutional facility such as a nursing home
  24. History or diagnosis of any of the following sleep conditions:

    1. Narcolepsy
    2. Cataplexy (familial or idiopathic)
    3. Circadian Rhythm Sleep Disorder
    4. Primary Hypersomnia
  25. Severe physical disability not associated with cognitive function that limits ability to complete neurocognitive testing (e.g., severe tremor, debilitating arthritis)
  26. Changes in medications or doses of medication in past 30 days prior to Screening

    1. All allowed concomitant medications, supplements, or other substances (with the exception of sleep, mood, cognitive and neuropsychiatric drugs) must be at stable doses for at least 30 days prior to screening and must be kept as stable as medically possible during the trial. Dosing change of ConMeds within 30 days of Screening may be allowed if in the opinion of the investigator, will not affect or influence study results.
    2. If a change in medication dosage occurs during the study, this will lead to discontinuation from study participation unless it relates to a medication that, in the view of the study investigator, does not affect participation in the trial.
    3. Allowed Sleep, Neuropsychiatric and Cognitive drugs must be stable for 90 days prior to Screening. Dosing change of Neuropsychiatric and Cognitive drugs within 90 days of Screening may be allowed if in the opinion of the investigator, will not affect or influence study results.
  27. Use of prohibited medications/substances.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03531684


Locations
Layout table for location information
United States, Ohio
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Neurocentria, Inc.
Ohio State University
Investigators
Layout table for investigator information
Principal Investigator: Douglas W Scharre, MD Ohio State University
Layout table for additonal information
Responsible Party: Neurocentria, Inc.
ClinicalTrials.gov Identifier: NCT03531684    
Other Study ID Numbers: NC007
First Posted: May 22, 2018    Key Record Dates
Last Update Posted: September 9, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders