Sirtuin-NAD Activator in Alzheimer's Disease

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Treatments: Niacin; Niacinamide; Nicotinic Acids

Criteria

Inclusion Criteria:

1. A man or a woman between the ages of 55 and 85 years (inclusive)

2. Meets National Institute on Aging-Alzheimer's Association (NIA-AA) clinical diagnostic criteria for AD dementia

3. Has evidence of AD pathological process by a positive amyloid assessment with cerebrospinal fluid (CSF) Aβ42

4. Has a Clinical Dementia Rating (CDR) global score of 0.5 or 1

5. Has a Mini-Mental State Exam (MMSE) Score of 18 to 26 (inclusive)

6. Has a 15-item Geriatric Depression Scale (GDS) score of < 6

7. 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)

8. 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

9. Has adequate visual and auditory acuity to participate in neuropsychological testing and other study assessments

10. Has the availability of an informant (study partner) who has regular contact with the participant and knows him/her well

11. Is willing and able to participate in all assessments in English

12. Is capable of providing written informed consent

Exclusion Criteria:

Subjects may not be enrolled if:

1. 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.

2. 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.

3. History of alcohol or substance use disorder or dependence (DSM V criteria) within the last 2 years.

4. 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.

5. Any significant systemic illness or unstable medical condition, which could obfuscate cognitive aging or neurodegenerative trajectories or affect valid cognitive and self-report measurements.

6. 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.

7. Current use of anticoagulants; significant back or spine disease that would make a lumbar puncture difficult or unsafe as determined by a clinician.

8. Other laboratory abnormalities: Has AST or ALT > 3 times the upper limit of normal; serum creatinine > 2.0 mg/d; HbA1C > 8.5%

9. Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter

10. Other medical conditions which, in the opinion of the investigator, would jeopardize safety or impact the validity of the study results.