NCT05344404: NR-SAFE

NR-SAFE: Safety of High-dose Nicotinamide Riboside (NR) in Parkinson's Disease

Completed NA Last updated 9 August 2022

What this trial tests

NA trial testing Nicotinamide Riboside in Parkinson Disease in 20 participants. Completed in 1 July 2022.

Timeline

29 April 2022

Primary endpoint
1 July 2022

1 July 2022

Quick facts

Lead sponsor	Haukeland University Hospital
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	20
Start date	29 April 2022
Primary completion	1 July 2022
Estimated completion	1 July 2022
Sites	1 location across Norway

Drugs / interventions tested

• Nicotinamide Riboside — full drug profile →
• Placebo

Conditions studied

• Parkinson Disease — all drugs for Parkinson Disease →

Sponsor

Haukeland University Hospital

Who can join

35 and older, any sex, with Parkinson Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

NR-SAFE is a double-blinded randomized safety study aiming to determine the safety and tolerability of nicotinamide riboside (NR) at a daily dose of 3000mg, in individuals with Parkinson's disease (PD).

The investigators recently reported the results of 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 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.

It is plausible that any beneficial effects of NR in PD may be dose-dependent and more pronounced at higher doses. NR doses of up to 2000mg daily have been tested in healthy humans with no signs of toxicity. However, the safety and tolerability of even higher doses is untested. To enable clinical studies assessing higher doses, the investigators will assess the safety and tolerability of an oral dose of 3000 mg NR daily.

NR-SAFE will recruit 20 participants with PD and randomize them 1:1 to either NR 3000mg daily or placebo for a total duration of 4 weeks.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease.
   Berven H, Kverneng S, Sheard E, Søgnen M, et al · · 2023 · cited 45× · PMID 38016950 · DOI 10.1038/s41467-023-43514-6
2. The Promise of Niacin in Neurology.
   Wuerch E, Urgoiti GR, Yong VW. · · 2023 · cited 38× · PMID 37084148 · DOI 10.1007/s13311-023-01376-2
3. Excitotoxicity, Oxytosis/Ferroptosis, and Neurodegeneration: Emerging Insights into Mitochondrial Mechanisms.
   Khan S, Bano N, Ahamad S, John U, et al · · 2024 · cited 17× · PMID 39122453 · DOI 10.14336/ad.2024.0125-1
4. Nicotinamide phosphoribosyltransferase in NAD<sup>+</sup> metabolism: physiological and pathophysiological implications.
   Zhang W, Ren H, Chen W, Hu B, et al · · 2025 · cited 12× · PMID 40775221 · DOI 10.1038/s41420-025-02672-w
5. Clinical Insights on Caloric Restriction Mimetics for Mitigating Brain Aging and Related Neurodegeneration.
   Trisal A, Singh AK. · · 2024 · cited 9× · PMID 39412683 · DOI 10.1007/s10571-024-01493-2
6. Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.
   Chen Z, Mao Z, Tang W, Shi Y, et al · · 2025 · cited 4× · PMID 41299782 · DOI 10.1186/s40035-025-00517-1
7. Clinical Trial Highlights: Modulators of Mitochondrial Function.
   Capriglia F, Burgess T, Bandmann O, Mortiboys H. · · 2023 · cited 1× · PMID 37694310 · DOI 10.3233/jpd-239003
8. Insights into the therapeutic strategies for aging and aging-associated diseases.
   Dong R, Wu Q, Kan J, Fu C, et al · · 2026 · PMID 42225652 · DOI 10.1038/s41392-026-02662-z