Sirtuin-NAD Activator in Alzheimer's Disease

NCT05040321 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2021P001366MIB-AD
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives are to:

1. 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. 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. 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).

Conditions

Alzheimer's Disease (Incl Subtypes); Dementia

Keywords

Dementia; NAD; MIB-626

Outcome Measures

Primary Outcomes (1)

• change in CSF concentrations of MIB-626

  change in CSF concentrations of MIB-626 at baseline and on day 90 at steady state

  90 days

Secondary Outcomes (4)

• change in CSF concentrations of MIB-626 metabolites, nicotinamide (NAM), NR, 2-PY, and MeNAM

  90 days

• change in the abundance of NAD in the brain using ultra-high field 7T magnetic resonance spectroscopy

  90 days

• change in NAD concentrations in peripheral blood mononuclear cells

  90 days

• change in the concentration of biomarkers of aging recommended (HbA1C, IGF1, T3, IL6, TNF-alpha, and urinary F2-isoprostane)

  90 days

Other Outcomes (5)

• 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)

  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)

  90

• Change in cognition

  90

Study Arms (2)

MIB-626

EXPERIMENTAL

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

Placebo Tablet

PLACEBO COMPARATOR

Subjects will be randomized to receive either the placebo or MIB-626 tablets twice a day orally.

Drug: Placebo

Interventions

MIB-626 DRUG

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.

MIB-626

Placebo DRUG

Subjects will be randomized to receive either the placebo or 1000 mg MIB-626 twice daily orally.

Placebo Tablet

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115-0000, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Shalender Bhasin, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Neha K Rupeja, MS

  Brigham and Women's Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind; the participants, care provider, investigators and outcome assessors are blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: We will use an IRB approved structured telephone screen to ask about basic demographics, major study required inclusion/exclusion criteria, and questions regarding MR contraindications. Those who do not have major exclusionary conditions identified during the telephone screening and who are interested in participating will be invited for an in-person visit. During the in-person screening visit, informed consent will be obtained, and subjects will undergo screening neuropsychological testing and medical evaluation. Subjects will come back after their initial screening visit for 2 more screening visits before they are found eligible and go through Baseline visits, also known as Day 0. Subjects will receive MIB-626 or placebo twice a day for 90 days. There will be one more visit, known as the washout period, at day 105. The total completion of all of the study visits will be 8 visits, for 150 days.

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: September 10, 2021
• Study Start: December 1, 2021
• Primary Completion: December 15, 2025
• Study Completion: April 30, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-02

Locations

US (1)