Parkinson DiseasePhase 2NCT05589766
N-DOSE: A Dose Optimization Trial of Nicotinamide Riboside in Parkinson's Disease
A Phase 2 study testing Nicotinamide Riboside in people with Parkinson Disease, run by Haukeland University Hospital at 1 site in Norway.
Trial summary
N-DOSE is a double-blinded placebo-controlled randomized trial aiming to determine the optimal biological dose (OBD) of nicotinamide riboside (NR), in individuals with Parkinson's disease (PD). Read more about this study
- Who is it for?
- Ages 40 to 100 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Nicotinamide Riboside
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 1 siteNorway
- Study dates
- 23 Jan 2023to 22 Apr 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 40 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinically established diagnosis of idiopathic PD according to the MDS criteria.
- 123I-Ioflupane dopamine transporter imaging (DAT-scan) confirming nigrostriatal degeneration.
- Hoehn and Yahr score < 4 at enrolment.
- Age ≥ 40 years at the time of enrollment.
- Able to undergo lumbar punction.
- Able to undergo MRI.
Who cannot join
- Dementia or other neurodegenerative disorder at baseline visit.
- Diagnosed with atypical parkinsonism (progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD)) or vascular parkinsonism.
- Any psychiatric disorder that would interfere with compliance in the study.
- Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
- Use of high dose vitamin B3 supplementation within 30 days of enrollment.
Trial locations and contacts
1 site in 1 country.
About this study
N-DOSE is a double-blinded placebo-controlled randomized trial aiming to determine the optimal biological dose (OBD) of nicotinamide riboside (NR), in individuals with Parkinson's disease (PD).
The investigators recently reported the NADPARK study (ClinicalTrials.gov: NCT03816020), a phase I randomized, double-blinded trial, assessing the tolerability, cerebral bioavailability and molecular effects of NR therapy, 1000mg daily, in PD. The NADPARK study showed that NR 1000mg daily was well tolerated and led to a significant, but variable, increase in cerebral NAD (nicotinamide adenine dinucleotide) levels (measured by 31phosphorous magnetic resonance spectroscopy, 31P-MRS) and related metabolites in the cerebrospinal fluid (CSF). NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography (FDG-PET), and this was associated with mild clinical improvement. The results of the NADPARK trial nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials. The investigators recently conducted the NR-SAFE safety trial comparing 3000mg NR to placebo in 20 participants with PD over 4 weeks (NCT: NCT05344404) which showed no moderate or severe adverse events, and no signs of acute toxicity.
Due to the variability in response to NR in the NADPARK trial, the N-DOSE study will investigate the response to escalating doses of NR from 1000 mg to 3000 mg over 12 weeks, in order to ascertain if NR dose escalation beyond 1000 mg per day is biologically meaningful in Parkinson's disease.
Read the detailed description
N-DOSE is a double-blinded placebo-controlled randomized trial aiming to determine the optimal biological dose (OBD) of nicotinamide riboside (NR), in individuals with Parkinson's disease (PD).
Individuals with PD (n = 80) will be recruited starting November 2022. Participants will be randomized 1:1:2 to either placebo group (PL-group; n = 20) or NR 1000mg daily (DS-group; n = 20) for 12 weeks or to a dose-escalation group (DE-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 -- Determine the safety and tolerability of NR doses 2000 mg and 3000 mg daily in PD, measured by the frequency and severity of adverse events.
- 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 PD-related pattern (PDRP) expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in PDRP 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 - motor \& 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 PD 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 PD 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 severity of non-motor symptoms of daily living in PD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and change in severity of non-motor symptoms of daily living in PD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on severity of motor aspects of experiences of daily living in PD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in severity of motor aspects of experiences of daily living in PD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on severity of PD motor symptoms at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in severity of PD motor 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 severity PD motor complications at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in severity of PD motor complications from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on clinical severity of PD non-motor symptoms at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in clinical severity of PD non-motor 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 clinical severity of gastrointestinal non-motor dysfunction in PD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in clinical severity of gastrointestinal non-motor dysfunction in PD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on cognition at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in cognition from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on quality of life in PD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in quality of life in PD 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 histone acetylation in PD 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 PD 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 PD 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 PD 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 PD 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 PD 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 PD 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 PD from 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 PD 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 PD 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 PD 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 PD 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.
- To compare the effect of orally administered NR in the DE-group versus DS-group on the sense of smell at week 12.
- To determine the safety and tolerability of NR at a dose of 1000 mg, 2000 mg, and 3000 mg per day in PD.
- 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 one of the neurologists involved in the study including MDS-UPDRS
- Clinical testing with MDS-NMS, MoCA, EQ-5L and modified GIDS-PD by one of the study nurses involved in the sudy
- 31P-MRS, 1H-MRS and FDG-PET scan.
- Physical examination and measurement of vital signs
- Routine blood tests
- Urine sample collection
- Fecal sample collection
- Cerebrospinal fluid collection will be performed at Baseline and week 12
- Conditions
- Parkinson Disease
- Being tested
- Nicotinamide Riboside, Placebo
- Keywords
- Parkinson's disease, NAD metabolism, Mitochondria, Nicotinamide Riboside
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide RibosideDietary supplement
Also called Niagen, NR
Nicotinamide Riboside supplementation up to 3000mg daily in total.
PlaceboOther
Placebo tablet identical in taste, form and appearance to NR tablets, administered twice daily for a total of 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo, no active ingredients. Administered in tablet form twice daily for the duration of the trial (12 weeks). Receives: Other: Placebo |
| Dietary Supplement: NR 1000mg group | Experimental | Nicotinamide Riboside 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 |
| Dietary Supplement: NR dose escalation group | Experimental | Nicotinamide Riboside 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 |
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 posted21 Oct 2022
- Study start23 Jan 2023
- Primary completion22 Apr 2025
- Study completion22 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson 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
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bergen
- Responsible party
- Sponsor
- Investigators
- Charalampos Tzoulis, PhD, Principal investigator, Neuro-Sysmed, Haukeland University Hospital and University of Bergen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05589766
- Sponsor's protocol ID
- 2022/426716
- Status last verified
- Jul 2025
- First submitted
- 13 Oct 2022
- Last updated
- 8 Jul 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 8 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-DOSE: A Dose Optimization Trial of Nicotinamide Riboside in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT05589766
- Acronym / sponsor ID
- 2022/426716
- Conditions
- Parkinson Disease
- Keywords
- Parkinson's disease, NAD metabolism, Mitochondria, Nicotinamide Riboside
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Collaborators
- University of Bergen
- Study start
- 23 Jan 2023 (actual)
- Primary completion
- 22 Apr 2025 (actual)
- Study completion
- 22 Apr 2025 (actual)
- First posted
- 21 Oct 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.
N-DOSE is a double-blinded placebo-controlled randomized trial aiming to determine the optimal biological dose (OBD) of nicotinamide riboside (NR), in individuals with Parkinson's disease (PD).
The investigators recently reported the NADPARK study (ClinicalTrials.gov: NCT03816020), a phase I randomized, double-blinded trial, assessing the tolerability, cerebral bioavailability and molecular effects of NR therapy, 1000mg daily, in PD. The NADPARK study showed that NR 1000mg daily was well tolerated and led to a significant, but variable, increase in cerebral NAD (nicotinamide adenine dinucleotide) levels (measured by 31phosphorous magnetic resonance spectroscopy, 31P-MRS) and related metabolites in the cerebrospinal fluid (CSF). NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography (FDG-PET), and this was associated with mild clinical improvement. The results of the NADPARK trial nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials. The investigators recently conducted the NR-SAFE safety trial comparing 3000mg NR to placebo in 20 participants with PD over 4 weeks (NCT: NCT05344404) which showed no moderate or severe adverse events, and no signs of acute toxicity.
Due to the variability in response to NR in the NADPARK trial, the N-DOSE study will investigate the response to escalating doses of NR from 1000 mg to 3000 mg over 12 weeks, in order to ascertain if NR dose escalation beyond 1000 mg per day is biologically meaningful in Parkinson's disease.
Detailed description
N-DOSE is a double-blinded placebo-controlled randomized trial aiming to determine the optimal biological dose (OBD) of nicotinamide riboside (NR), in individuals with Parkinson's disease (PD).
Individuals with PD (n = 80) will be recruited starting November 2022. Participants will be randomized 1:1:2 to either placebo group (PL-group; n = 20) or NR 1000mg daily (DS-group; n = 20) for 12 weeks or to a dose-escalation group (DE-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 -- Determine the safety and tolerability of NR doses 2000 mg and 3000 mg daily in PD, measured by the frequency and severity of adverse events.
- 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 PD-related pattern (PDRP) expression at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in PDRP 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 - motor \& 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 PD 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 PD 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 severity of non-motor symptoms of daily living in PD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and change in severity of non-motor symptoms of daily living in PD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on severity of motor aspects of experiences of daily living in PD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in severity of motor aspects of experiences of daily living in PD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on severity of PD motor symptoms at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in severity of PD motor 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 severity PD motor complications at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in severity of PD motor complications from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on clinical severity of PD non-motor symptoms at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in clinical severity of PD non-motor 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 clinical severity of gastrointestinal non-motor dysfunction in PD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in clinical severity of gastrointestinal non-motor dysfunction in PD from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on cognition at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in cognition from baseline to weeks 4, 8 and 12.
- To compare the effect of orally administered NR in the DE-group versus DS-group on quality of life in PD at week 12.
- To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in quality of life in PD 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 histone acetylation in PD 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 PD 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 PD 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 PD 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 PD 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 PD 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 PD 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 PD from 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 PD 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 PD 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 PD 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 PD 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.
- To compare the effect of orally administered NR in the DE-group versus DS-group on the sense of smell at week 12.
- To determine the safety and tolerability of NR at a dose of 1000 mg, 2000 mg, and 3000 mg per day in PD.
- 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 one of the neurologists involved in the study including MDS-UPDRS
- Clinical testing with MDS-NMS, MoCA, EQ-5L and modified GIDS-PD by one of the study nurses involved in the sudy
- 31P-MRS, 1H-MRS and FDG-PET scan.
- Physical examination and measurement of vital signs
- Routine blood tests
- Urine sample collection
- Fecal sample collection
- Cerebrospinal fluid 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 tablet form twice daily for the duration of the trial (12 weeks). |
| Dietary Supplement: NR 1000mg group | Experimental | Dietary Supplement: Nicotinamide RibosideNicotinamide Riboside 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 RibosideNicotinamide Riboside 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
- 40 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Clinically established diagnosis of idiopathic PD according to the MDS criteria.
- 123I-Ioflupane dopamine transporter imaging (DAT-scan) confirming nigrostriatal degeneration.
- Hoehn and Yahr score < 4 at enrolment.
- Age ≥ 40 years at the time of enrollment.
- Able to undergo lumbar punction.
Key exclusion criteria (5 listed)
- Dementia or other neurodegenerative disorder at baseline visit.
- Diagnosed with atypical parkinsonism (progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD)) or vascular parkinsonism.
- Any psychiatric disorder that would interfere with compliance in the study.
- Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
- 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 |
|---|---|---|
| Nicotinamide RibosideAlso: Niagen, NRNicotinamide Riboside supplementation up to 3000mg daily in total. | Dietary supplement | Dietary Supplement: NR 1000mg group, Dietary Supplement: NR dose escalation group |
| PlaceboPlacebo tablet identical in taste, form and appearance to NR tablets, administered twice daily for a total of 12 weeks. | Other | Placebo |
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 8 Jul 2025.
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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.
Charalampos Tzoulis, PhD principal investigator
Neuro-Sysmed, Haukeland University Hospital and University of Bergen
1 site 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 in people with Parkinson Disease, run by Haukeland University Hospital at 1 site 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 6 inclusion and 5 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 8 Jul 2025. 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 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 8 Jul 2025.