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

NCT ID: NCT04430517

Last Updated: 2025-10-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-02
• Study Completion Date: 2026-01-30

Brief 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).

Detailed Description

Mitochondrial function is mediated, in part, by nicotinamide adenine dinucleotide (NAD). Unfortunately, decreases in NAD+ levels are associated with normal aging, and also with numerous diseases such as AD. Accumulating evidence suggests that NR can enhance mitochondrial function and help slow or reverse these age-related abnormalities. Numerous preclinical and clinical studies have been performed using NR and related compounds to boost NAD+ level in human subjects with various diseases or animal models. However, no studies to date have investigated in vivo metabolic and bioenergetic changes (target engagement) associated with NR supplementation. In this project, we aim to investigate the neurobiological mechanisms and clinical effects of NR in patients with MCI and mild AD using in vivo novel neuroimaging techniques.

Conditions

Mild Cognitive Impairment; Mild Alzheimer Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Mild Cognitive Impairment and Alzheimer's Dementia

Participants will take 4 pills every day, each containing 250 mg NR (NIAGEN® by Chromadex; www.chromadex.com), via the oral route, for 12 weeks.

Group Type: EXPERIMENTAL

Nicotinamide riboside

Intervention Type: DRUG

Participants will take 4 pills every day, each containing 250 mg NR (NIAGEN® by Chromadex; www.chromadex.com), via the oral route, for 12 weeks.

Interventions

Nicotinamide riboside

Participants will take 4 pills every day, each containing 250 mg NR (NIAGEN® by Chromadex; www.chromadex.com), via the oral route, for 12 weeks.

Intervention Type: DRUG

Other Intervention Names

Chromadex NIAGEN

Eligibility 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. 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 or AD+ including Amyloid positive PET scan, Tau positive PET Scan (MK6240 et al.), or CSF AD biomarkers [i.e., amyloid-beta beta (Aβ42) total (T)-tau, and phosphorylated (P)-tau]
• 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, centrally acting 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 carnitine, creatine Co-Q10, N-acetyl cysteine [NAC], pramipexole)
• Initiation of treatment or change in dosing of acetylcholinesterase inhibitors (AChEIs) and memantine within 4 weeks of baseline visit
• Prior use of prescription narcotics 4 weeks before baseline visit
• 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.
• Current or lifetime history of cancer.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Mclean Hospital

OTHER

Sponsor Role: lead

Responsible Party

Fei Du

Director, Laboratory for High-Field Imaging and Translational Neuroscience

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fei Du, PhD

Role: PRINCIPAL_INVESTIGATOR

Mclean Hospital

Brent Forester, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Mclean Hospital

Locations

McLean Hospital

Belmont, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Fei Du, PhD

Role: CONTACT

fdu@mclean.harvard.edu

6178552710

Facility Contacts

Fei Du, PhD

Role: primary

fdu@mclean.harvard.edu

(617) 855-2710

Brent Forester, MD, MSc

Role: backup

bforester@partners.org

(617) 855-3622

Other Identifiers

1R01AG066670

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2020P001652

Identifier Type: -

Identifier Source: org_study_id