Alzheimer DiseasePhase 2NCT05617508
N-DOSE AD: A Dose Optimization Trial of Nicotinamide Riboside in Alzheimer's Disease
A Phase 2 study testing Nicotinamide Riboside supplementation 1000mg daily in total and Nicotinamide Riboside dose escalation (up to 3000 mg daily in total) in people with Alzheimer Disease and Dementia, run by Haukeland University Hospital at 2 sites in Norway.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease, Dementia
- What is being tested?
- Nicotinamide Riboside supplementation 1000mg daily in total and Nicotinamide Riboside dose escalation (up to 3000 mg daily in total)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 2 sitesNorway
- Study dates
- 22 Nov 2022to 5 Jun 2025
- Phase
- Phase 2
- 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 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
Who cannot join
- 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.
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- 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
Trial locations and contacts
2 sites in 1 country.
Norway2 sites
Haraldsplass Deaconess Hospital
Bergen, Vestland, 5009
Haukeland University Hospital
Bergen, Vestland, 5021
About this study
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:
Read more
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.
Read the detailed description
N-DOSE AD is a double-blinded placebo-controlled randomized trial aiming to determine the optimal biological dose (OBD) of nicotinamide riboside (NR), in individuals with Alzheimer's disease (AD).
Individuals with AD (n = 80) will be recruited starting November 2022. Participants will be randomized 1:1:2 to either placebo group (n = 20) or NR 1000mg daily (n = 20) for 12 weeks or to a dose-escalation group where NR 1000mg daily will be administered week 1-4, NR 2000mg daily week 5-8 and NR 3000mg daily week 9-12 (n =40). Both the participants and the investigators will be blinded.
- Primary Objective: -- To compare the effect of orally administered nicotinamide riboside (NR), escalated to 1500 mg twice per day (3000 mg/day) in the dose escalation group (DE-group) - versus stable dosing of 500 mg twice per day (1000 mg/day) in the dose-stable group (DS-group) on cerebral NAD levels, at week 12.
- Secondary Objectives:
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in cerebral NAD levels from baseline to weeks 4, 8 and 12.
- To compare the effectiveness of orally administered nicotinamide riboside (NR) 1500 mg twice per day versus 500 mg twice per day in augmenting the NAD-metabolome in the central nervous system (CNS) at week 12.
- Safety Objectives -- To determine the safety and tolerability of NR at a dose of 1000 mg, 2000 mg, and 3000 mg per day in AD.
- Exploratory Objectives:
- Neuroimaging
- To compare the effect of orally administered NR in the DE-group versus DS-group on the NR related metabolic pattern (NRRP) expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in NRRP expression from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR DE-group versus DS-group on the AD-related pattern (ADRP) expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in ADRP expression from baseline to weeks 4, 8 and 12.
- Metabolism \& molecular markers
- To compare the effect of orally administered NR in the DE-group versus DS-group on the NAD metabolome* in the blood, urine and central nervous system (CNS) at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in the NAD metabolome* in blood and urine from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on serum and CSF inflammatory markers at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in serum inflammatory markers from baseline to weeks 4, 8 and 12.
- Clinical - cognitive \& non motor symptom severity, quality of life
- To compare the effect of orally administered NR in the DE-group versus DS-group on clinical severity of AD symptoms at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and change in clinical severity of AD symptoms from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on ADL severity in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and change in ADL scores in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on depressive symptoms in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and depressive symptoms in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on neuropsychiatric symptoms in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and change in neuropsychiatric symptoms in AD from baseline to weeks 4, 8 and 12.
- Hypothesis-generating or resource-dependent endpoints (may be reported in follow-up or secondary publications).
- To compare the effect of orally administered NR in the DE-group versus DS-group on gene expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in gene expression from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on protein expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in protein expression from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on serum and CSF inflammatory markers at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in serum inflammatory markers from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on histone acetylation in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in histone acetylation in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on H3K27 and H4K16 histone acetylation in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in on H3K27 and H4K16 histone acetylation in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on the genomic distribution of H3K27 and H4K16 histone acetylation in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in the genomic distribution of H3K27 and H4K16 histone acetylation in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on folate and one-carbon metabolism in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in folate and one-carbon metabolism in AD rom baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on methyl donors in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in methyl-donors in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on DNA methylation at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in methyl-donors in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on synthesis of neurotransmitters in AD at week 12.
- Determine whether NR-therapy affects the gut microbiome in a dose-responsive manner at week 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on the gut metabolome at week 12.
- Procedures:
All participants will attend study visits at Baseline, week 4, week 8 and week 12. The study visits will consist of the following:
Assessment by physician and study nurse involved in the study including The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Clinical Dementia Rating (CDR), Montreal Cognitive Assessment Test (MoCA), Trail Making Test (TMT), The Lawton Instrumental Activities of Daily Living Scale (IADL), The Physical Self-Maintenance Scale (PSMS), Montgomery-Asberg Depression Rating Scale (MADRS), the The Neuropsychiatric Inventory Questionnaire (NPI-Q)
A 31P-magnetic resonance spectroscopy (MRS), 1H-magnetic resonance spectroscopy (MRS) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scan.
Physical examination and measurement of vital signs. Routine blood tests. Urine sample collection. Faecal sample collection at Baseline and week 12. Cerebrospinal fluid (CSF) collection will be performed at Baseline and week 12.
- Conditions
- Alzheimer Disease, Dementia
- Being tested
- Placebo, Nicotinamide Riboside supplementation 1000mg daily in total, Nicotinamide Riboside dose escalation (up to 3000 mg daily in total)
- Keywords
- NAD metabolism, Mitochondria, Nicotinamide Riboside
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Placebo capsules administered twice daily for a total of 12 weeks.
Nicotinamide Riboside supplementation 1000mg daily in totalDietary supplement
Also called Niagen, NR
Nicotinamide Riboside supplementation 1000mg daily in total
Nicotinamide Riboside dose escalation (up to 3000 mg daily in total)Dietary supplement
Also called Niagen, NR
Nicotinamide Riboside supplementation up to 3000mg daily in total
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo, no active ingredients. Administered in capsule form twice daily for the duration of the trial (12 weeks). Receives: 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). Receives: 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). Receives: Dietary Supplement: Nicotinamide Riboside dose escalation (up to 3000 mg daily in total) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Change in the cerebrospinal fluid (CSF) levels of NAD or other metabolites of the NAD metabolome*, measured by LC-MS.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2022
- Study start22 Nov 2022
- Primary completion5 Jun 2025
- Study completion5 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Haraldsplass Deaconess Hospital
- Responsible party
- Sponsor
- Investigators
- Kristoffer Haugarvoll, MD, PhD, Principal investigator, Haukeland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05617508
- Sponsor's protocol ID
- 428878
- Status last verified
- Jun 2025
- First submitted
- 7 Nov 2022
- Last updated
- 1 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-DOSE AD: A Dose Optimization Trial of Nicotinamide Riboside in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT05617508
- Acronym / sponsor ID
- 428878
- Conditions
- Alzheimer Disease, Dementia
- Keywords
- NAD metabolism, Mitochondria, Nicotinamide Riboside
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Collaborators
- Haraldsplass Deaconess Hospital
- Study start
- 22 Nov 2022 (actual)
- Primary completion
- 5 Jun 2025 (actual)
- Study completion
- 5 Jun 2025 (actual)
- First posted
- 15 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
N-DOSE AD is a double-blinded placebo-controlled randomized trial aiming to determine the optimal biological dose (OBD) of nicotinamide riboside (NR), in individuals with Alzheimer's disease (AD).
Individuals with AD (n = 80) will be recruited starting November 2022. Participants will be randomized 1:1:2 to either placebo group (n = 20) or NR 1000mg daily (n = 20) for 12 weeks or to a dose-escalation group where NR 1000mg daily will be administered week 1-4, NR 2000mg daily week 5-8 and NR 3000mg daily week 9-12 (n =40). Both the participants and the investigators will be blinded.
- Primary Objective: -- To compare the effect of orally administered nicotinamide riboside (NR), escalated to 1500 mg twice per day (3000 mg/day) in the dose escalation group (DE-group) - versus stable dosing of 500 mg twice per day (1000 mg/day) in the dose-stable group (DS-group) on cerebral NAD levels, at week 12.
- Secondary Objectives:
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in cerebral NAD levels from baseline to weeks 4, 8 and 12.
- To compare the effectiveness of orally administered nicotinamide riboside (NR) 1500 mg twice per day versus 500 mg twice per day in augmenting the NAD-metabolome in the central nervous system (CNS) at week 12.
- Safety Objectives -- To determine the safety and tolerability of NR at a dose of 1000 mg, 2000 mg, and 3000 mg per day in AD.
- Exploratory Objectives:
- Neuroimaging
- To compare the effect of orally administered NR in the DE-group versus DS-group on the NR related metabolic pattern (NRRP) expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in NRRP expression from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR DE-group versus DS-group on the AD-related pattern (ADRP) expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in ADRP expression from baseline to weeks 4, 8 and 12.
- Metabolism \& molecular markers
- To compare the effect of orally administered NR in the DE-group versus DS-group on the NAD metabolome* in the blood, urine and central nervous system (CNS) at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in the NAD metabolome* in blood and urine from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on serum and CSF inflammatory markers at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in serum inflammatory markers from baseline to weeks 4, 8 and 12.
- Clinical - cognitive \& non motor symptom severity, quality of life
- To compare the effect of orally administered NR in the DE-group versus DS-group on clinical severity of AD symptoms at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and change in clinical severity of AD symptoms from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on ADL severity in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and change in ADL scores in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on depressive symptoms in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and depressive symptoms in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on neuropsychiatric symptoms in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and change in neuropsychiatric symptoms in AD from baseline to weeks 4, 8 and 12.
- Hypothesis-generating or resource-dependent endpoints (may be reported in follow-up or secondary publications).
- To compare the effect of orally administered NR in the DE-group versus DS-group on gene expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in gene expression from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on protein expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in protein expression from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on serum and CSF inflammatory markers at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in serum inflammatory markers from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on histone acetylation in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in histone acetylation in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on H3K27 and H4K16 histone acetylation in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in on H3K27 and H4K16 histone acetylation in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on the genomic distribution of H3K27 and H4K16 histone acetylation in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in the genomic distribution of H3K27 and H4K16 histone acetylation in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on folate and one-carbon metabolism in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in folate and one-carbon metabolism in AD rom baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on methyl donors in AD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in methyl-donors in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on DNA methylation at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in methyl-donors in AD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on synthesis of neurotransmitters in AD at week 12.
- Determine whether NR-therapy affects the gut microbiome in a dose-responsive manner at week 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on the gut metabolome at week 12.
- Procedures:
All participants will attend study visits at Baseline, week 4, week 8 and week 12. The study visits will consist of the following:
Assessment by physician and study nurse involved in the study including The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Clinical Dementia Rating (CDR), Montreal Cognitive Assessment Test (MoCA), Trail Making Test (TMT), The Lawton Instrumental Activities of Daily Living Scale (IADL), The Physical Self-Maintenance Scale (PSMS), Montgomery-Asberg Depression Rating Scale (MADRS), the The Neuropsychiatric Inventory Questionnaire (NPI-Q)
A 31P-magnetic resonance spectroscopy (MRS), 1H-magnetic resonance spectroscopy (MRS) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scan.
Physical examination and measurement of vital signs. Routine blood tests. Urine sample collection. Faecal sample collection at Baseline and week 12. Cerebrospinal fluid (CSF) collection will be performed at Baseline and week 12.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboPlacebo, no active ingredients. Administered in capsule form twice daily for the duration of the trial (12 weeks). |
| Dietary Supplement: NR 1000 mg group | Experimental | Dietary Supplement: Nicotinamide Riboside supplementation 1000mg daily in totalNicotinamide 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: NR dose escalation group | Experimental | Dietary Supplement: Nicotinamide Riboside dose escalation (up to 3000 mg daily in total)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). |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- The following condition must apply to the prospective patient at screening prior to receiving study agent:
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo capsules administered twice daily for a total of 12 weeks. | Other | Placebo |
| Nicotinamide Riboside supplementation 1000mg daily in totalAlso: Niagen, NRNicotinamide Riboside supplementation 1000mg daily in total | Dietary supplement | Dietary Supplement: NR 1000 mg group |
| Nicotinamide Riboside dose escalation (up to 3000 mg daily in total)Also: Niagen, NRNicotinamide Riboside supplementation up to 3000mg daily in total | Dietary supplement | Dietary Supplement: NR dose escalation group |
Primary outcome
Cerebral NAD levels measured by 31P-MRS
Time frame: 12 weeks for primary analysis. 4, 8 and 12 weeks for secondary analysis.
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).
1 secondary outcome
CSF NAD or other metabolite of the NAD metabolome, measured by LC-MS
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2025.
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Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristoffer Haugarvoll, MD, PhD principal investigator
Haukeland University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nicotinamide Riboside supplementation 1000mg daily in total and Nicotinamide Riboside dose escalation (up to 3000 mg daily in total) in people with Alzheimer Disease and Dementia, run by Haukeland University Hospital at 2 sites in Norway.
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 9 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 1 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. 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. Some participants in this study may receive a placebo. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Cerebral NAD levels measured by 31P-MRS (time frame: 12 weeks for primary analysis. 4, 8 and 12 weeks for secondary analysis.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Dec 2025.