Effects of Nicotinamide Riboside on Bioenergetics and Oxidative Stress in Mild Cognitive Impairment/Alzheimer's Dementia

• Status: Recruiting
• Trial end date: 2025-04-30
• Target enrollment: 0
• Participant gender: All

Summary

The primary aim of this study is to investigate the effects of exogenously administered nicotinamide riboside (NR) on brain energy metabolism, oxidative stress, and cognitive function in individuals with mild cognitive impairment (MCI) and mild Alzheimer's dementia (AD).

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mclean Hospital
• Collaborator: National Institute on Aging (NIA)
• Treatments: Niacin; Niacinamide; Nicotinic Acids

Criteria

Inclusion Criteria:

• Ability of the participant and/or his/her legally authorized representative to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information.

• Ability to speak and read fluently in English

• 55-89 years old (inclusive)

• Normal or corrected to normal hearing and vision

• Meet clinical diagnostic criteria for MCI or Mild AD, according to the following criteria:

1. CDR Global Score of 0.5 (MCI) or 1.0 (mild AD)

2. MoCA total score of 19-25 (MCI) or 11-21 (mild AD)

3. 2018 NIA-AA guidelines for MCI/mild AD

• Study partner available for the duration of trial participation

• At least one copy of the APOE ε4 allele

• An aggregate risk score > 4 according to the risk analysis method developed by Sabbagh et al. (2017)

• For individuals who are taking niacin (or a vitamin supplement with niacin) of >200mg, the completion of a two-week wash-out period

Exclusion Criteria:

• Current serious or unstable medical or neurological condition that could affect cognitive functioning, as determined by study clinician

• Clinically unstable mood or anxiety disorder within 6 months prior to screening, as determined by study clinician

• Lifetime history of psychotic disorder (i.e. Schizophrenia, Schizoaffective Disorder), as determined by study clinician

• Diagnosis of a mitochondrial disorder

• Any MRI safety contraindications

• History of drug hypersensitivity or intolerance to NR

• Transient ischemic attack or stroke within 1 year prior to screening

• History of alcohol or substance abuse within prior year, as determined by study clinician and urine toxicology screen

• History of head injury rated as moderate or worse, per DSM-5 criteria

• History of seizure within prior 10 years

• Current use of medication with known adverse effects on cognition (benzodiazepines, barbiturates, opiate analgesics, first generation antipsychotic medication, anticholinergics, sedating antihistamines, tricyclic anti-depressants)

• Change in dose of any psychiatric medications within 4 weeks of screening visit

• Prior use of L-DOPA, any anti-Parkinsonian medication, or prior treatment with anti-amyloid immunotherapy

• Current use of putative mitochondrial enhancers and antioxidants (e.g Vitamin E, carnitine, creatine Co-Q10, pramipexole, N-acetyl cysteine [NAC])

• Initiation of treatment or change in dosing of acetylcholinesterase inhibitors (AChEIs) and memantine within 4 weeks of screening

• Prior use of prescription narcotics 4 weeks before screening

• Female subjects who are pregnant or breastfeeding

• The use of current use of niacin (or a vitamin supplement with niacin) >200mg within the last two weeks prior to study visit.