Alzheimer Disease
Conditions
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.
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.
Interventions
DIETARY_SUPPLEMENTMMFS-205-SR
Twice daily, oral, 500 mg tablets
DIETARY_SUPPLEMENTPlacebo
Twice daily, oral
Sponsors
Ohio State University
Neurocentria, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neuropsychological Test Battery (NTB) standardized composite score | 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. |
| Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) score | 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
| Measure | Time frame | Description |
|---|---|---|
| Modified Mini-Mental State Examination (mMMSE) total score | 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. |
| Alzheimer's Disease Cooperative Scale-Activities of Daily Living-Mild Cognitive Impairment 24 questions (ADCS-ADL-MCI24) | 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. |
| Alzheimer's Disease Cooperative Scale - Clinical Global Impression of Change (ADCS-MCI-CGIC) score | 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). |
| Neuropsychiatric Inventory (NPI) sub score | 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
| Measure | Time frame | Description |
|---|---|---|
| Responder analyses of Modified Mini-Mental State Examination (mMMSE) | 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 |
| Physical Activity Scale for the Elderly (PASE) | Change from baseline at 12 and 24 weeks | The PASE is a short survey designed to assess physical activity specifically in elderly. |
| Insulin resistance markers | Change from baseline at 12 and 24 weeks | HbA1c and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR): fasting glucose and insulin |
| Neuropsychological Test Battery cognitive domain analyses | 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) |
| Geriatric Depression Scale (GDS) | 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. |
| Brief Smell Identification Test (BSIT) score | 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. |
| Neuropsychiatric Inventory (NPI) total score | 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. |
| Neuropsychological Test Battery (NTB) standardized composite score at 12 weeks | 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. |
| Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) score at 12 weeks | 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. |
Countries
United States
Outcome results
None listed