A Phase 2 interventional study of Placebo and Nicotinamide Riboside supplementation 1000mg daily in total in Alzheimer Disease and Dementia, sponsored by Haukeland University Hospital. Completed at 2 sites in Norway. Open to participants aged 50 Years to 85 Years. Per ClinicalTrials.gov, last updated 2025-12-01.
Sponsored by Haukeland University Hospital · Phase 2, Interventional, and Treatment
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.
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:
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:
Hypothesis-generating or resource-dependent endpoints (may be reported in follow-up or secondary publications).
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.
3,675 studies on the registry are indexed under Alzheimer Disease; 869 are open to participants now.
This study's enrollment of 80 is above the median of 70 across 2,805 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →Haukeland University Hospital is the lead sponsor of 276 studies on the registry; 61 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The following condition must apply to the prospective patient at screening prior to receiving study agent:
Exclusion Criteria:
Patients will be excluded from the study if they meet any of the following criteria:
Placebo, no active ingredients. Administered in capsule form twice daily for the duration of the trial (12 weeks).
Other: Placebo
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
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)
Placebo capsules administered twice daily for a total of 12 weeks.
Nicotinamide Riboside supplementation 1000mg daily in total
Also known as: Niagen, NR
Nicotinamide Riboside supplementation up to 3000mg daily in total
Also known as: Niagen, NR
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).
Time frame: 12 weeks for primary analysis. 4, 8 and 12 weeks for secondary analysis.
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.
Time frame: 12 weeks
Frequency and severity of adverse events
The between-visit difference in incidence of treatment-associated mild/moderate/severe adverse events (AEs)
Time frame: 12 weeks
Change in gene and protein expression levels related to lysosomal and proteasomal function
The between-visit change in gene and protein expression levels related to lysosomal and proteasomal function in whole blood, measured by RNA sequencing (RNAseq) and proteomics (LC-MS), respectively.
Time frame: 12 weeks
Change in levels of one carbon metabolism metabolites
The between-visit change in one carbon metabolism/methylation pathway metabolites. Measured by HPLC-MS metabolomics in whole blood and CSF.
Time frame: 12 weeks
Between-change in depressive symptoms, measured by Montgomery-Asberg Depression Rating Scale (MADRS)
MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Time frame: 12 weeks
Between-visit change in neuropsychiatric symptoms, measured by Change in Neuropsychiatric Inventory brief questionnaire form (NPI-Q)
The NPI-Q measures the burden of 12 neuropsychiatric symptoms of dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating. Symptom severity is rated on a 3-point scale with higher scores indicating worse symptoms. Minimum score would be 0 and maximum score would be 36.
Time frame: 12 Weeks
Between-visit change in the Physical Self-Maintenance Scale (PSMS)
The PSMS includes 6 items, testing the following areas: toilet use, eating, dressing, physical appearance, deambulation and bath. The PSMS ranges from 1 to 30, with higher scores indicating WORSE functioning.
Time frame: 12 weeks
Between-visit change in the Lawton Instrumental Activities of Daily Living (IADL) Scale
The IADL scale consists of 8 items providing information about telephone use, preparing food, shopping, doing daily household chores, doing laundry, using transport, medication managing, and managing money. Scores range from 0 (dependent) to 8 (independent).
Time frame: 12 weeks
The between-visit change in executive functioning measured by the Trail Making Test (TMT)
The TMT is a timed test and the goal is to complete the test as accurately and as quickly as possible. Raw scores are reported in seconds to complete the test. For Part B, an average score is 75 seconds and a deficient score is greater than 273 seconds.
Time frame: 12 weeks
Between-visit change cognitive function measured by the Montreal Cognitive Assessment (MoCA) scale
MoCA scale (minimum score = 0, maximum score = 30) and a dichotomized cut-off score for normality of 26 or over. High scores indicate less cognitive impairment than low scores.
Time frame: 12 weeks
The between-visit chang in Clinical Dementia Rating scale sum of boxes (CDR-SB)
The 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 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.
Time frame: 12 weeks
Determining the between-visit change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13)
The ADAS-Cog 13 is a psychometric instrument that evaluates memory, attention, reasoning, language, concentration, planning, executive function, and praxis using an 13-point AD Assessment Scale. It has a minimum score of 0 and a maximum severity score of 85, and a higher score indicates more impairment. A reduction in between-visit scores indicates an improvement in cognitive functions.
Time frame: 12 weeks
Change in levels of monoamine neurotransmitters in CSF
The between-visit difference in levels of monoamine neurotransmitters in CSF.
Time frame: 12 weeks
Change in genomic distribution of DNA methylation
The between-visit difference in genomic distribution of DNA methylation, measured by the Illumina Infinium MethylationEPIC Kit.
Time frame: 12 weeks
Change in levels of DNA methylation
The between-visit difference in levels of DNA methylation, measured by the Illumina Infinium MethylationEPIC Kit.
Time frame: 12 weeks
Change in levels of histone acetylation
The between-visit difference in levels of histone panacetylation, and levels of site specific histone acetylation in whole blood, measured by immunoblotting and chromatin immunoprecipitation sequencing (ChIPseq).
Time frame: 12 weeks
Change in genomic distribution of histone acetylation
The between-visit difference in genomic distribution of histone acetylation in whole blood, measured by immunoblotting and chromatin immunoprecipitation sequencing (ChIPseq).
Time frame: 12 weeks
Change in gut microbiome composition
The between-visit difference in gut microbiome composition, assessed by metagenomics in fecal samples.
Time frame: 12 weeks
Change in faecal metabolomics
The between-visit difference in fecal metabolomics, including fatty acid profiling
Time frame: 12 weeks
Change in levels of inflammatory cytokines in serum and CSF
The between-visit difference in levels of inflammatory cytokines in serum and CSF, measured using the ELISA method.
Time frame: 12 weeks
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Haukeland University Hospital