Sirtuin-NAD Activator in Alzheimer's Disease

Completed · Phase 1/Phase 2 · Has a placebo group

Conditions studied: Alzheimer's Disease (Incl Subtypes), Dementia

In brief

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).

Key facts

Study ID: NCT05040321
Run by: Brigham and Women's Hospital
People needed: 22
Starts: 2021-12-01
Expected to finish: 2026-04-30
Last updated by the study team: 2026-07-01

Who can join

Age: 55 and older, up to 85. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

Subjects may not be enrolled if:
Neurologic diseases: Any significant neurologic disease other than AD that can lead to cognitive impairment, such as Parkinson's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia, Huntington's disease, normal pressure hydrocephalus, corticobasal syndrome, brain tumor, seizure disorder, subdural hematoma (within the last 1 year), multiple sclerosis, or history of significant head trauma (e.g. loss of consciousness for 30 minutes or more) followed by persistent neurologic deficits or known structural brain abnormalities.
Neuroimaging: Baseline or prior magnetic resonance imaging (MRI) scans with evidence of cortical stroke or hemorrhage, strategically located lacunar stroke (ex: left thalamus), or severe small vessel ischemic disease.
History of alcohol or substance use disorder or dependence (DSM V criteria) within the last 2 years.
Psychiatric disorder: Major depressive disorder (within the last 1 year), bipolar disorder, schizophrenia (DSM V criteria), or current major psychotic symptoms or behavioral problems that could interfere with study procedures.
Any significant systemic illness or unstable medical condition, which could obfuscate cognitive aging or neurodegenerative trajectories or affect valid cognitive and self-report measurements.
Excluded medications: Niacin or dietary supplements containing nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR); antipsychotic medications, antidepressant medications with anticholinergic side effects. Washout from psychoactive medications for at least 8 weeks before screening.
Current use of anticoagulants; significant back or spine disease that would make a lumbar puncture difficult or unsafe as determined by a clinician.
Other laboratory abnormalities: Has AST or ALT > 3 times the upper limit of normal; serum creatinine > 2.0 mg/d; HbA1C > 8.5%
Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter
Other medical conditions which, in the opinion of the investigator, would jeopardize safety or impact the validity of the study results.

Where it is running

Brigham and Women's Hospital — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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