This protocol describes the NOPARK Open Label Extension Study. The NOPARK Open Label Extension study is an optional extension of the clinical phase II NOPARK study. Participants who have been included in the NOPARK study will upon completing their participation in the NOPARK study (i.e., after 52 weeks) be offered to receive the study drug Nicotinamide Riboside (NR) 1200 mg P.O. per day, until the NOPARK trial is completed, and the data analyzed with a conclusion of the primary outcome. Individuals enrolled into the NOPARK Open Label Extension Study will be followed with yearly visits. The goal of the NOPARK Open Label Extension Study is to monitor long term safety and study long term neuroprotective and other biological effects of NR use.

The primary objective of the NOPARK open label extension study is to monitor NR use for long term safety. The secondary objective of the NOPARK open label study is to monitor long term NR use among PD patients and observe the clinical progression of PD. The NOPARK open label extension study is an open label study, where subjects enrolled in the NOPARK study (ClinicalTrials.gov: NCT03816020), upon completion of the study, will be offered the NR study drug for continuous use, until the NOPARK study is completed and the primary end-point assessed (31/12/2025). The dose of NR is 1200mg NR daily, divided into 600mg twice daily. The reason for the slightly higher dose compared to NOPARK (i.e., 200mg higher) is the fact that the active compound is now available in capsules of 300mg which cannot be divided. From a clinical and scientific perspective, given current knowledge of safety and efficacy of NR in PD, a dose of 1200 mg is both safe and of a higher potential benefit to patients. The study is multi-site, identical to NOPARK. The primary endpoint of the study, which is safety, will be analyzed using descriptive statistics. The secondary endpoint, which is if long-term NR use delays PD progression will be analyzed using the clinical MDS-UPDRS score. Exploratory objectives will assess PD progression relative to the general PD-population and whether long-term NR use affects methylation metabolism. Stratification of analyses is dependent on the duration of administered NR, sex and age. Exploratory stratification will be done based on results from biological data analysis based on data from NOPARK or blood samples collected in the NOPARK open label extension study.

Inclusion Criteria:

• Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study

Participated in the NOPARK study

Exclusion Criteria:

• Current use of vitamin B3 supplementation or NR supplementation - other than in relation to the NOPARK study

Known allergic reactions to components of the NR

Physical or psychiatric illness that makes them unavailable for follow-up and participation.

All data supporting te publication will be publicly shared with the exception of any sensitive information which can lead to participant identification, as defined by Norwegian law.

At publication

We will publish open access. The data will be publicly available