A Proof of Concept Trial of a Sirtuin-NAD Activator in Alzheimer's Disease
The primary objectives are to: 1. To determine whether MIB-626, after its daily oral administration, penetrates the blood-brain barrier in humans by measuring the cerebrospinal fluid (CSF) concentrations of MIB-626 and its key metabolites, nicotinamide (NAM), NR, 2-PY, and MeNAM at baseline and on day 90 at steady state. 2. To evaluate whether oral MIB-626 administration engages the sirtuin-NAD pathway by determining the abundance of NAD (a SIRT1 substrate) in the brain using ultra-high field 7T magnetic resonance spectroscopy and in peripheral blood mononuclear cells using a validated LC-MS/MS assay. 3. To determine whether MIB-626 alters the circulating biomarkers of aging that the geroscience experts have recommended (HbA1C, IGF1, T3, IL6, TNF, and urinary F2-isoprostane).
• A man or a woman between the ages of 55 and 85 years (inclusive)
• Meets National Institute on Aging-Alzheimer's Association (NIA-AA) clinical diagnostic criteria for AD dementia
• Has evidence of AD pathological process by a positive amyloid assessment with cerebrospinal fluid (CSF) Aβ42
• Has a Clinical Dementia Rating (CDR) global score of 0.5 or 1
• Has a Mini-Mental State Exam (MMSE) Score of 18 to 26 (inclusive)
• Has a 15-item Geriatric Depression Scale (GDS) score of \< 6
• Impaired memory performance below education adjusted cut-off score on the Logical Memory II subscale delayed paragraph recall (LM-IIa) of the Wechsler Memory Scale-Revised (WMS-R) (≥16 years: ≤8; 8-15 years: ≤4; 0-7 years: ≤2)
• May take Food and Drug Administration (FDA) approved medications for the treatment of AD dementia (cholinesterase inhibitors and/or memantine), but if taking such medications, they must be stable for at least 8 weeks before screening
• Has adequate visual and auditory acuity to participate in neuropsychological testing and other study assessments
⁃ Has the availability of an informant (study partner) who has regular contact with the participant and knows him/her well
⁃ Is willing and able to participate in all assessments in English
⁃ Is capable of providing written informed consent