N-AD: A Randomized, Double Blind, Parallel Group, Placebo Controlled, Phase 2 Trial of Orally Administered Nicotinamide Riboside Over Two Years as a Potential Disease Modifying Treatment for Alzheimer's Disease

NCT07741071 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 481035
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn if orally administered nicotinamide riboside works to slow the progression of early Alzheimer disease in adults. It will also learn about the safety of drug nicotinamide riboside. The main questions it aims to answer are:

• Does drug nicotinamide riboside slow the progression of Alzheimer disease as measured by the Clinical Dementia Rating scale.
• What medical problems do participants have when taking drug nicotinamide riboside? Researchers will compare drug nicotinamide riboside to a placebo (a look-alike substance that contains no drug) to see if nicotinamide riboside works to treat early Alzheimer disease. Participants will:
• Take drug nicotinamide ribosie or a placebo every day for 24 months
• Visit the clinic once every 26 weeks for checkups and tests

Conditions

Alzheimer Disease (AD)

Keywords

Alzheimer's Disease (AD); mild cognitive impairment; Nicotinamide riboside; Dementia; Placebo controlled

Outcome Measures

Primary Outcomes (1)

• Disease severity assessed by the Clinical Dementia Rating scale (CDR) sum of boxes.

  CDR is a scale assessing clinical impairment in AD. CDR integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following semi-structured caregiver interview and systematic participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The "Sum of boxes" scoring methodology (CDR-SB) sums the score for each of the 6 domains and provides a value ranging from 0 to 18 with higher scores indicating greater impairment. Positive change from baseline indicates greater impairment.

  From baseline to the end of treatment at 104 weeks.

Secondary Outcomes (6)

• Change from baseline in the MoCA score at Week 104.

  From baseline to the end of treatment at 104 weeks.

• Change from baseline in Amsterdam ADL scale short version (A-IADL-Q-SV) at Week 104.

  From baseline to the end of treatment at 104 weeks

• Change from baseline in delayed recall performance on the CERAD 10-Word List at Week 104

  From baseline to the end of treatment at 104 weeks.

• Change from baseline in executive functioning as measured by Trail-Making Test Part B completion time at Week 104

  From baseline to the end of treatment at 104 weeks.

• Change from baseline in verbal fluency as measured by the COWAT (total correct words for F, A, S) at Week 104.

  From baseline to the end of treatment at 104 weeks.

Other Outcomes (3)

• Change from baseline in plasma p-tau217 levels at 104 weeks

  From baseline to end of treatment at week 104.

• Change from baseline in plasma MTBR-tau243 levels at 104 weeks

  From baseline to end of treatment at 104 weeks.

• Frequency and severity of adverse events

  From baseline to end of treatment at 104 weeks.

Study Arms (2)

Nicotinamide Riboside (NR)

EXPERIMENTAL

Nicotinamide riboside, 2000 mg for the duration of the trial (104 weeks). Dosage form is capsules.

Dietary Supplement: Nicotinamide Riboside (NR)

Placebo

PLACEBO COMPARATOR

Placebo capsules, no active ingredients.

Other: Palacebo

Interventions

Nicotinamide Riboside (NR) DIETARY_SUPPLEMENT

Nicotinamide Riboside 1000mg administered two times a day. Given as capsules. Duration of the trial; 104 weeks.

Also known as: NR, TruNiagen

Nicotinamide Riboside (NR)

Palacebo OTHER

Placebo drug, administered two times a day. Given as capsules. Duration of the trial; 104 weeks.

Placebo

Eligibility Criteria

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

You may qualify if:

• Diagnosis Early clinical AD, e.g. Stage 3 MCI or Stage 4 (mild AD dementia), as defined by the FDA, 2024.
• Biomarker evidence consistent with AD neuropathologic change, defined by CSF markers, i.e. Aβ42 \< 1030 ng/L and P-tau181/Aβ42 \> 0,023 ng/L and/or T-tau/Aβ42 \> 0,28 ng/L\* or AD amyloid biomarker (as determined either by visual reading of amyloid PET scans using an approved ligand
• Diagnosed with AD within 2 years from baseline.
• 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, this will be determined by an evaluation by a consultant clinician who is not associated with the N-AD study.
• Global CDR(33) 0.5-1 (inclusive) at enrollment.
• Age 50 to 85 years (inclusive) at the time of enrollment.
• A study partner with sufficient contact to be able to provide data on ADLs and assist the participant in study drug administration. -
• Cholinesterase inhibitors and memantine can be used if stable for 8 weeks prior to baseline visit.

You may not qualify if:

• Diagnosis of dementia other than probable AD.
• Abundant vascular pathology, i.e. Fazekas \>2. or \>3 lacunar infarcts, stroke involving a major vascular territory, severe small vessel, or white matter disease
• More than 1 core feature of dementia with Lewy bodies, i.e; recurrent visual hallucination, cognitive fluctuations, REM sleep behaviour disorder, one or more spontaneous cardinal features of parkinsonism (tremor, rigidity and bradykinesia).
• Comorbidity that precludes study participation or data interpretation.
• Any psychiatric disorder that would interfere with compliance in the study.
• Use of high dose vitamin B3 supplementation within 30 days of baseline.
• Any active neoplastic malignancy (other than non-metastatic dermatological conditions) within two years of the screening visit or current clinically significant haematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease. Active neoplastic malignancy is defined as having a known malignant focus and/or receiving anti-cancer treatment. For the non-cancer conditions, if the condition has been stable for at least the one year before the screening visit and/or is judged by the site investigator not to interfere with the subject's participation in the study, the subject may be included.
• Inability to undergo MRI or to comply with study procedures.

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (2)

Haraldsplass Deaconess Hospital

Bergen, 5009, Norway

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Dementia

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

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

Study Officials

• Kristoffer Haugarvoll, MD, PhD

  Haukeland University Hospital

  STUDY DIRECTOR

Central Study Contacts

Kristoffer Haugarvoll, MD, PhD

CONTACT

47-55975045; kristoffer.haugarvoll@helse-bergen.no

Study Design

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

Model Details: Randomized double-blinded study. N = 270 participants are randomized in a 1:1 ratio to either nicotinamide riboside (1000 mg x 2 per day) or placebo.

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: August 3, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): April 30, 2030
• Last Updated: August 3, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2)