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Mild Cognitive ImpairmentEarly Phase 1NCT04430517

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

A Early Phase 1 study testing Nicotinamide riboside in people with Mild Cognitive Impairment and Mild Alzheimer Disease, run by Mclean Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 55 to 89 years
What is being tested?
Nicotinamide riboside
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
2 Mar 2022to 29 Apr 2026
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 89 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • CDR Global Score of 0.5 (MCI) or 1.0 (mild AD)
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • McLean Hospital

    Belmont, Massachusetts, 02478

Other trials in United States

About this study

Official title: Effects of Orally Administered Nicotinamide Riboside on Bioenergetic Metabolism, Oxidative Stress and Cognition in Mild Cognitive Impairment and Mild Alzheimer's Dementia

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).

Read the 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.

Being tested
Nicotinamide riboside
Keywords
Mild Cognitive Impairment, Bioenergetics, Mild Alzheimer's Dementia
Medical subject headings
Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nicotinamide ribosideDrug

    Also called Chromadex NIAGEN

    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.

Study groups in NCT04430517
Study groupRoleWhat they receive
Mild Cognitive Impairment and Alzheimer's DementiaExperimentalParticipants will take 4 pills every day, each containing 250 mg NR (NIAGEN® by Chromadex; www.chromadex.com), via the oral route, for 12 weeks.
Receives: Drug: Nicotinamide riboside

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in brain NAD+

    Changes in brain NAD+ levels

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

  2. Changes in brain redox state

    Changes in brain NAD+/NADH ratio

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

Secondary outcomes (2)

  1. Changes in mitochondrial function

    Changes in brain CK/ATPase activity

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

  2. Changes in antioxidant glutathione (GSH) levels

    Changes in brain GSH levels

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2020
  2. Study start2 Mar 2022
  3. Primary completion29 Apr 2026
  4. Study completion29 Apr 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04430517
Sponsor's protocol ID
2020P001652
Other IDs
1R01AG066670
Status last verified
Jun 2026
First submitted
29 May 2020
Last updated
30 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The proposed research will include data and biosamples from 50 subjects who will receive open-label treatment with nicotinamide riboside (NR) throughout the duration of the 12-week study. 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.

Publications

  • Zhang SQ, Lee J, Pan JP, Enger R, Hrubos-Strom H, Musiek ES, Fang EF, Le W. NAD+-circadian rhythm coupling in dementia. Alzheimers Dement. 2026 May;22(5):e71360. doi: 10.1002/alz.71360.

    PubMed 42063312

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Nicotinamide riboside in people with Mild Cognitive Impairment and Mild Alzheimer Disease, run by Mclean Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in brain NAD+ (time frame: Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04430517, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2026.

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