N-DOSE AD: A Dose Optimization Trial of Nicotinamide Riboside in Alzheimer's Disease

NCT05617508 | Completed Phase 2

• 1 other identifier: 428878
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this double-blinded placebo-controlled randomized trial is to determine the optimal dose of nicotinamide riboside (NR), in individuals with Alzheimer's disease (AD). The main questions the N-DOSE AD trial aims to answer are: What dose of nicotinamide riboside (NR) is required to achieve maximal cerebral nicotinamide adenine dinucleotide (NAD) increase, measured by 31P-magnetic resonance spectroscopy (MRS) or cerebrospinal fluid (CSF) metabolomics)? What dose of nicotinamide riboside (NR) is required to achieve maximal alteration in the cerebral metabolism patterns, measured by fluorodeoxyglucose-positron emission tomography (FDG-PET)? What dose of nicotinamide riboside (NR) will have optimal effect in the absence of unacceptable toxicity? Participants will be asked to do participate in: Clinical examinations Cognitive assessments Lumbar puncture Magnetic resonance imaging - positron emission tomography (MRI-PET) scannings Biosampling They'll be given placebo, 1000 mg NR or escalating doses of NR (1000 mg - 2000 mg - 3000 mg) over 12 weeks.

Conditions

Alzheimer Disease; Dementia

Keywords

NAD metabolism; Mitochondria; Nicotinamide Riboside

Outcome Measures

Primary Outcomes (1)

• Cerebral NAD levels measured by 31P-MRS

  Change in cerebral NAD/ATP-α ratio measured by 31 Phosphorus magnetic resonance spectroscopy (31P-MRS) in the posterior brain (encompassing the occipital, parietooccipital and posterior parts of the temporal cortex).

  12 weeks for primary analysis. 4, 8 and 12 weeks for secondary analysis.

Secondary Outcomes (1)

• CSF NAD or other metabolite of the NAD metabolome, measured by LC-MS

  12 weeks

Other Outcomes (19)

• Frequency and severity of adverse events

  12 weeks

• Change in gene and protein expression levels related to lysosomal and proteasomal function

  12 weeks

• Change in levels of one carbon metabolism metabolites

  12 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo, no active ingredients. Administered in capsule form twice daily for the duration of the trial (12 weeks).

Other: Placebo

Dietary Supplement: NR 1000 mg group

EXPERIMENTAL

Nicotinamide Riboside (NR) 1000mg total daily. Administered in capsule form in doses of 500mg twice daily for the duration of the trial (12 weeks).

Dietary Supplement: Nicotinamide Riboside supplementation 1000mg daily in total

Dietary Supplement: NR dose escalation group

EXPERIMENTAL

Nicotinamide Riboside (NR) dose escalation group: 1000mg NR daily in doses of 500mg twice daily (week 1 - week 4), 2000mg NR daily in doses of 1000mg twice daily (week 5 - week 8), 3000mg NR daily in doses of 1500mg twice daily (week 9 - week 12).

Dietary Supplement: Nicotinamide Riboside dose escalation (up to 3000 mg daily in total)

Interventions

Placebo OTHER

Placebo capsules administered twice daily for a total of 12 weeks.

Placebo

Nicotinamide Riboside supplementation 1000mg daily in total DIETARY_SUPPLEMENT

Nicotinamide Riboside supplementation 1000mg daily in total

Also known as: Niagen, NR

Dietary Supplement: NR 1000 mg group

Nicotinamide Riboside dose escalation (up to 3000 mg daily in total) DIETARY_SUPPLEMENT

Nicotinamide Riboside supplementation up to 3000mg daily in total

Also known as: Niagen, NR

Dietary Supplement: NR dose escalation group

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The following condition must apply to the prospective patient at screening prior to receiving study agent:
• Diagnosis of probable Alzheimer Disease (AD) according to the core clinical criteria updated in the National Institute on Aging (NIA) and Alzheimer's Association guidelines.
• Biomarker evidence consistent with AD neuropathologic change, defined by cerebrospinal fluid (CSF) markers.
• Diagnosed with AD within two years from enrollment.
• Clinical Dementia Rating (CDR) 0.5-1 (inclusive) at enrollment.
• Age 50 to 85 years (inclusive) at the time of enrollment.
• A study partner (i.e. a family member or a friend) able to provide study data and assist the participant in the study drug administration, i.e. contact ≥ 3 times weekly.
• Capacity to provide written informed consent for study participation defined as Montreal Cognitive Assessment (MoCA) score ≥ 16 or Mini Mental State Evaluation (MMSE) score ≥ 20. MMSE or MoCA must have been performed within 6 months prior to baseline. If there is any doubt regarding the participants capacity to give informed consent we will ask for an independent evaluation by a consultant clinician who is not associated with the N-DOSE AD study.
• Cholinesterase inhibitors and memantine can be used if stable for 8 weeks prior to baseline visit.
• Able to undergo lumbar puncture.
• Able to undergo magnetic resonance imaging (MRI)

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Diagnosis of dementia other than probable AD.
• Comorbidity that precludes study participation or data interpretation.
• Any psychiatric disorder that would interfere with compliance in the study.
• Any severe somatic illness that would interfere with compliance and participation in the study.
• Use of high dose vitamin B3 supplementation within 30 days of enrollment.
• Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
• Current treatment with Oral Anti-coagulation Therapies
• Implants that preclude MRI examinations, e.g. DBS, pacemaker

Sponsors & Collaborators

• Haukeland University Hospital: lead
• Haraldsplass Deaconess Hospital: collaborator

Study Sites (2)

Haraldsplass Deaconess Hospital

Bergen, Vestland, 5009, Norway

Location

Haukeland University Hospital

Bergen, Vestland, 5021, Norway

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Kristoffer Haugarvoll, MD, PhD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Both participants and all investigators are blinded during the trial and during data analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized double-blinded placebo-controlled study. 80 participants randomized in 1:1:2 ratio to either: 1. Placebo (n=20), 2. NR 1000mg for 3 months (n=20), 3. Dose escalation group: NR 1000mg 1st month, NR 2000mg 2nd month, NR 3000mg 3rd month (n=40).

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 15, 2022
• Study Start: November 22, 2022
• Primary Completion: June 5, 2025
• Study Completion: June 5, 2025
• Last Updated: December 1, 2025

Record last verified: 2025-06

Locations

NO (2)