Disease: Parkinson's disease
Type of study: Interventional trial
Coordinating investigator: Haakon Berven
Study director: Charalampos Tzoulis
Background: While our previous findings nominate NR as therapy for PD, the observed effects were heterogeneous across the study population, raising the question of individualised dose-dependent responses. The optimal NR dose for neurological intervention is unknown, and doses over 2000 mg daily have not been evaluated in humans. To be able to conduct a dose optimisation study for NR in PD (see the N-DOSE study), we first must establish the range of safe dosage. Here, we will conduct a safety and tolerability trial of 3000 mg oral NR in PD.
The primary objective of the NR-SAFE study is to determine the safety of oral NR 3000 mg daily for a period of 4 weeks in individuals with Parkinson’s disease (PD). Safety is defined as the absence of clinically significant NR-associated moderate or severe adverse events (AE).
Design: NR-SAFE is a randomised double-blinded placebo-controlled trial to assess the safety and tolerability of NR at a dose of 3000 mg per day. Twenty individuals with PD will receive NR 3000 mg or placebo (1:1 randomisation) and followed with frequent laboratory and clinical examinations for 30 days.
Primary endpoint: The Incidence of treatment-associated moderate and severe AEs.
Status: The study was completed and published in 2023. No NR-related adverse events or signs of toxicity were observed. NR-recipients exhibited a pronounced augmentation of the NAD metabolome, with up to 5-fold increase in blood NAD+ levels, and a significant improvement in the total MDS-UPDRS, by 10.7 ± 9.94 points (p = 0.007). These results establish that short-term NR treatment at a dose of 3000 mg daily is safe, induces a pronounced augmentation of the NAD metabolome, and may be associated with a clinical symptomatic improvement in PD. While these findings do not guarantee long-term safety, they allow for a dose range extension of NR employed in clinical trials up to 3000 mg daily, provided appropriate safety monitoring. This will be important for determining potential dose-dependent beneficial effects of NR in PD and other disorders (see the N-DOSE and N-DOSE_ AD trials). The study was published in the journal Nature Communications (PMID: 38016950).
Participating centre
- Haukeland University Hospital, Bergen
Funding
- The Research Council of Norway, Neuro-SysMed
The Regional Health Authority of Western Norway
Haukeland University Hospital