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

NCT04430517 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 2020P0016521R01AG066670
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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).

Conditions

Mild Cognitive Impairment; Mild Alzheimer Disease

Keywords

Mild Cognitive Impairment; Bioenergetics; Mild Alzheimer's Dementia

Outcome Measures

Primary Outcomes (2)

• Changes in brain NAD+

  Changes in brain NAD+ levels

  Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily

• Changes in brain redox state

  Changes in brain NAD+/NADH ratio

  Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily

Secondary Outcomes (2)

• Changes in mitochondrial function

  Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily

• Changes in antioxidant glutathione (GSH) levels

  Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily

Other Outcomes (5)

• Changes in cognitive status

  Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily

• Changes in functional status

  Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily

• Changes in mood

  Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily

Study Arms (1)

Mild Cognitive Impairment and Alzheimer's Dementia

EXPERIMENTAL

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.

Drug: Nicotinamide riboside

Interventions

Nicotinamide riboside 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.

Also known as: Chromadex NIAGEN

Mild Cognitive Impairment and Alzheimer's Dementia

Eligibility Criteria

• Age: 55 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:
• CDR Global Score of 0.5 (MCI) or 1.0 (mild AD)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mclean Hospital: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Fei Du, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

• Brent Forester, MD, MSc

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Laboratory for High-Field Imaging and Translational Neuroscience

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 12, 2020
• Study Start: March 2, 2022
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: At the time of publication of the primary results or within 9 months of database lock, whichever comes first, we will create deidentified datasets, which could be available for research purposes to qualified individuals within the scientific community.
• Access Criteria: Data are available to users only under a data-sharing agreement. All users will provide to PIs a proposal of hypotheses, variables needed to test these hypotheses, and plans for dissemination of findings. All users will indicate in a signed document: (1) a commitment to using the data only for research purposes and not to identify any participant, clinician, or plan; (2) a plan for securing the data using appropriate technology/data use protocols; (3) an agreement to either destroy or return the data once analyses are completed or by a specific negotiated date; (4) appropriate IRB approval; (5) a commitment that the information provided to users will not be used for commercial purposes, will not be redistributed to third parties, or shared with any others not on the research team; (6) adequate funding/resources to analyze the data and publish results. All findings generated will be described via peer-reviewed articles in scientific journals made available via PubMed Central.

Locations

US (1)