A Phase 1/2 interventional study of MIB-626 and Placebo in Alzheimer's Disease (Incl Subtypes) and Dementia, sponsored by Brigham and Women's Hospital. Completed at 1 site in United States. Open to participants aged 55 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-07-01.
Sponsored by Brigham and Women's Hospital · Phase 1/2, Interventional, and Treatment
The primary objectives are to:
The sirtuin family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylase enzymes are important regulators of the aging process and mediate many of the beneficial effects of caloric restriction. The upregulation of the sirtuin-NAD pathway by increasing intracellular NAD through administration of NAD precursors, such as niacinamide β nicotinamide mononucleotide (βNMN) and nicotinamide riboside, has been shown to engage fundamental mechanisms of aging and prevent or attenuate Alzheimer's disease (AD) pathology in preclinical models. In contrast to many AD drugs in development that target one mechanism, NAD precursors may prevent AD pathology by multiple mechanisms: by improving mitochondrial energetics; inducing a switch to non-amyloidogenic processing of amyloid precursor protein (APP) due to increased α-secretase activity; reducing the synthesis of oligomerized Aβ peptides; preventing microglia-dependent Aβ toxicity; attenuating neuroinflammation; promoting neuronal regeneration; and improving insulin action.
In spite of the promising preclinical data, the human studies of the clinical pharmacology, physiologic effects, efficacy, and safety of NAD precursors have been few and constrained by several methodological barriers. First, βNMN and nicotinamide riboside (NR) are sold as dietary supplements and these over-the-counter products have suffered from variable manufacturing quality. Second, there is only limited information available on the pharmacokinetics (PK) and pharmacodynamics (PD) of βNMN and NR in humans, and the doses used in some initial studies were low. Third, NAD and many other metabolites of βNMN and NR are labile and susceptible to rapid degradation ex vivo. Furthermore, the assays for the measurement of intracellular NAD, βNMN, and its metabolites have been challenging. Although NR and βNMN have been shown to cross the blood-brain barrier, attenuate AD pathology, and improve cognitive function in preclinical models, no clinical trials have been conducted to determine whether βNMN crosses the blood-brain barrier or engages the target mechanisms in humans.
To overcome these methodological barriers, we have characterized the pharmacokinetics of MIB-626 in phase 1 studies, validated the methods for measuring intracellular NAD, and established the procedures for blood collection to ensure pre-analytical stability. These phase 1 studies have shown that a regimen of 1 g MIB-626 twice daily is safe and effective in substantially raising circulating NAD levels in healthy adults (preliminary data). These foundational methods and single and multiple-dose pharmacokinetic studies have paved the way for the proposed 90-day randomized trial in 24 mild AD dementia participants to determine whether MIB-626 crosses the blood-brain barrier, engages the hypothesized target mechanism, and whether it improves the biomarkers of aging. We hypothesize that MIB-626 administration at the proposed dose will cross the blood-brain barrier and be associated with an increase in brain NAD. Because of the important role of the sirtuin-NAD pathway in regulation of the mechanisms of aging, we will also assess whether MIB-626 is more efficacious than placebo in improving biomarkers of aging in participants with mild AD dementia.
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This study's enrollment of 22 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
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Exclusion Criteria:
Subjects may not be enrolled if:
Subjects will either take MIB-626 or placebo tablet twice a day for 90 days. For those who receive MIB-626, we plan on giving subjects 1000mg of the drug, twice a day for 90 days. MIB-626 will be in two 500mg tablets.
Drug: MIB-626
Subjects will be randomized to receive either the placebo or MIB-626 tablets twice a day orally.
Drug: Placebo
Participants will be randomized to either receive MIB-626 or matching placebo. The proposed intervention - targets multiple contributors to the pathology of AD; MIB-626 improves mitochondrial function, bioenergetics, and insulin sensitivity, inhibits A beta accumulation by reducing its synthesis and increasing its clearance, reduces neuroinflammation, exerts neuronal protective effects, and promotes neuronal regeneration and connectivity in preclinical models.
Subjects will be randomized to receive either the placebo or 1000 mg MIB-626 twice daily orally.
change in CSF concentrations of MIB-626
change in CSF concentrations of MIB-626 at baseline and on day 90 at steady state
Time frame: 90 days
change in CSF concentrations of MIB-626 metabolites, nicotinamide (NAM), NR, 2-PY, and MeNAM
change from baseline to day 90 in CSF concentrations of MIB-626 metabolites NAM, NR, 2-PY and MeNAM The concentrations of MIB-626's metabolites NAM, NR, 2-PY, and MeNAM will be measured in the CSF
Time frame: 90 days
change in the abundance of NAD in the brain using ultra-high field 7T magnetic resonance spectroscopy
change from baseline to day 90 in the abundance of NAD in the brain using ultra-high field 7T magnetic resonance spectroscopy
Time frame: 90 days
change in NAD concentrations in peripheral blood mononuclear cells
change from baseline to day 90 in NAD concentrations in peripheral blood mononuclear cells using validated LC-MS/MS assay
Time frame: 90 days
change in the concentration of biomarkers of aging recommended (HbA1C, IGF1, T3, IL6, TNF-alpha, and urinary F2-isoprostane)
change from baseline to day 90 in the concentration of biomarkers of aging recommended (HbA1C, IGF1, T3, IL6, TNF-alpha, and urinary F2-isoprostane)
Time frame: 90 days
change in CSF concentrations of biomarkers of amyloid deposition (Aβ-42, Aβ-40), neuronal/axonal degeneration (t-tau, p-tau, NFL), synaptic function (neurogranin) and neuroinflammation (YKL40, GFAP)
change from baseline to day 90 in CSF concentrations of biomarkers of amyloid deposition (Aβ-42, Aβ-40).
Time frame: 90 days
Change in circulating biomarkers of amyloid deposition (Aβ-42, Aβ-40), neuronal/axonal degeneration (t-tau, p-tau, NFL), synaptic function (neurogranin), and neuroinflammation (YKL40, GFAP)
Change from baseline to day 90 in circulating biomarkers of amyloid deposition (Aβ-42, Aβ-40), neuronal/axonal degeneration (t-tau, p-tau, NFL), synaptic function (neurogranin), and neuroinflammation (YKL40, GFAP)
Time frame: 90
Change in cognition
Change from baseline to day 90 in cognition, assessed using the Alzheimer's Disease Assessment Scale cognitive subscale 13-item version (ADAS-Cog-13)
Time frame: 90
Change in instrumental activities of daily living (IADL)
Change from baseline to day 90 in the Functional Activities Questionnaire (FAQ) score
Time frame: 90
Change in neuropsychiatric symptoms
Change from baseline to day 90 in Neuropsychiatric Inventory (NPI) score and 15-item GDS scale score
Time frame: 90
This study is completed, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Brigham and Women's Hospital