NOPARK Open Label Extension Study

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.

Study Overview

• Status: Recruiting
• Conditions: Safety Issues
• Intervention / Treatment: Dietary supplement: Nicotinamide Riboside

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Charalampos Tzoulis, PhD; Phone Number: +47 94392305; Email: [email protected]

Study Locations

• Norway
  • Vestland
    • Bergen, Vestland, Norway, 5021
      • Recruiting
      • Haukeland University Hospital
      • Contact: Charalampos Tzoulis, PhD; Phone Number: +47 94392305; Email: [email protected]
      • Contact: Haakon Berven, MD; Phone Number: +47 48495197; Email: [email protected]
      • Principal Investigator: Charalampos Tzoulis, PhD
      • Sub-Investigator: Haakon Berven, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotinamide Riboside; Open Label. Nicotinamide Riboside 1200mg x1 daily	Dietary supplement: Nicotinamide Riboside; 1200mg x1 Nicotinamide Riboside

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: measurement of Adverse Events	To assess the safety profile of long-term treatment with oral NR 1200 mg daily.	0-3 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Outcome: total movement disorders society unified Parkinson disease rating scale (MDS-UPDRS) score. Range 0-199	To assess whether the progression of PD during the NOPARK open label extension study differs among individuals who used placebo and individuals who used NR for 52 weeks in the NOPARK study.	0-3 Years

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Principal Investigator: Charalampos Tzoulis, PhD, Neur-Sysmed, Haukeland University Hospital, Norway

Publications and helpful links

General Publications

• Brakedal B, Dolle C, Riemer F, Ma Y, Nido GS, Skeie GO, Craven AR, Schwarzlmuller T, Brekke N, Diab J, Sverkeli L, Skjeie V, Varhaug K, Tysnes OB, Peng S, Haugarvoll K, Ziegler M, Gruner R, Eidelberg D, Tzoulis C. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metab. 2022 Mar 1;34(3):396-407.e6. doi: 10.1016/j.cmet.2022.02.001.
• Dollerup OL, Christensen B, Svart M, Schmidt MS, Sulek K, Ringgaard S, Stodkilde-Jorgensen H, Moller N, Brenner C, Treebak JT, Jessen N. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr. 2018 Aug 1;108(2):343-353. doi: 10.1093/ajcn/nqy132.
• Conze DB, Crespo-Barreto J, Kruger CL. Safety assessment of nicotinamide riboside, a form of vitamin B3. Hum Exp Toxicol. 2016 Nov;35(11):1149-1160. doi: 10.1177/0960327115626254. Epub 2016 Jul 11. Erratum In: Hum Exp Toxicol. 2018 Apr;37(4):448.
• Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 2019 Jul 5;9(1):9772. doi: 10.1038/s41598-019-46120-z.
• EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, Castenmiller J, De Henauw S, Hirsch-Ernst KI, Maciuk A, Mangelsdorf I, McArdle HJ, Naska A, Pelaez C, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Cubadda F, Frenzel T, Heinonen M, Prieto Maradona M, Marchelli R, Neuhauser-Berthold M, Poulsen M, Schlatter JR, van Loveren H, Albert O, de Sesmaisons Lecarre A, Knutsen HK. Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2021 Nov 12;19(11):e06843. doi: 10.2903/j.efsa.2021.6843. eCollection 2021 Nov.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Actual): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 25, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Parkinson's disease; Nicotinamide Riboside; Open Label
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 457567

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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.
• IPD Sharing Time Frame: At publication
• IPD Sharing Access Criteria: We will publish open access. The data will be publicly available
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No