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

NCT05589766 | Completed Phase 2

• 1 other identifier: 2022/426716
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Parkinson Disease

Keywords

Parkinson's disease; 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 (30)

• Safety, measured by the frequency and severity of adverse events

  12 weeks

• Expression of the Nicotinamide Riboside Related Pattern (NRRP).

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

• Expression of the Parkinsons Disease Related Pattern (PDRP).

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

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

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).

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).

Dietary Supplement: Nicotinamide Riboside

Interventions

Nicotinamide Riboside DIETARY_SUPPLEMENT

Nicotinamide Riboside supplementation up to 3000mg daily in total.

Also known as: Niagen, NR

Dietary Supplement: NR 1000mg group; Dietary Supplement: NR dose escalation group

Placebo OTHER

Placebo tablet identical in taste, form and appearance to NR tablets, administered twice daily for a total of 12 weeks.

Placebo

Eligibility Criteria

• Age: 40 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinically established diagnosis of idiopathic PD according to the MDS criteria.
• I-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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Haukeland University Hospital: lead
• University of Bergen: collaborator

Study Sites (1)

Haukeland University Hospital

Bergen, Vestland, 5021, Norway

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Charalampos Tzoulis, PhD

  Neuro-Sysmed, Haukeland University Hospital and University of Bergen

  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: October 13, 2022
• First Posted: October 21, 2022
• Study Start: January 23, 2023
• Primary Completion: April 22, 2025
• Study Completion: April 22, 2025
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

NO (1)