Efficacy and Safety of MMFS in Early AD

Clinical Trial to Test the Efficacy and Safety of MMFS-205 in Early Alzheimer's Disease Patients

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Dietary supplement: MMFS-205-SR; Dietary supplement: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Inactive sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological Test Battery (NTB) standardized composite score	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.	Change from baseline at 24 weeks
Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) score	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.	Change from baseline at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Mini-Mental State Examination (mMMSE) total score	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.	Change from baseline at 12 and 24 weeks
Alzheimer's Disease Cooperative Scale-Activities of Daily Living-Mild Cognitive Impairment 24 questions (ADCS-ADL-MCI24)	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.	Change from baseline at 12 and 24 weeks
Alzheimer's Disease Cooperative Scale - Clinical Global Impression of Change (ADCS-MCI-CGIC) score	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).	Change from baseline at 12 and 24 weeks
Neuropsychiatric Inventory (NPI) sub score	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.	Change from baseline at 12 and 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Activity Scale for the Elderly (PASE)	The PASE is a short survey designed to assess physical activity specifically in elderly.	Change from baseline at 12 and 24 weeks
Geriatric Depression Scale (GDS)	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.	Change from baseline at 12 and 24 weeks
Brief Smell Identification Test (BSIT) score	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.	Change from baseline at 12 and 24 weeks
Neuropsychiatric Inventory (NPI) total score	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.	Change from baseline at 12 and 24 weeks
Neuropsychological Test Battery (NTB) standardized composite score at 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.	12 weeks
Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) score at 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.	12 weeks
Responder analyses of Modified Mini-Mental State Examination (mMMSE)	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	Change from baseline at 12 and 24 weeks
Neuropsychological Test Battery cognitive domain analyses	Analysis of individual cognitive tests comprising the Neuropsychological Test Battery (NTB)	Change from baseline at 12 and 24 weeks, or change from baseline at 24 weeks, as appropriate
Insulin resistance markers	HbA1c and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR): fasting glucose and insulin	Change from baseline at 12 and 24 weeks

Collaborators and Investigators

• Sponsor: Neurocentria, Inc.
• Collaborators: Ohio State University
• Investigators: Principal Investigator: Douglas W Scharre, MD, Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2018
• Primary Completion (Actual): April 22, 2020
• Study Completion (Actual): April 22, 2020

Study Registration Dates

• First Submitted: April 4, 2018
• First Submitted That Met QC Criteria: May 8, 2018
• First Posted (Actual): May 22, 2018

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: NC007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No