A Randomized Controlled Trial of Nicotinamide Supplementation in Early Parkinson's Disease
A Randomized Controlled Trial of Nicotinamide Supplementation in Early Parkinson's Disease
NOPARK is a double-blinded randomized controlled trial that studies nicotinamide
 supplementation in early Parkinson's disease.

 Parkinson's disease (PD) is a major cause of death and disability and has a worldwide
 socioeconomic impact. It affects ~2% of the population above the age of 65 years and its
 prevalence increases dramatically as the population ages. The etiology and molecular
 pathogenesis underlying PD remain unknown. Recent evidence has implicated an impaired
 neuronal metabolism due to mitochondrial dysfunction, in particular NAD-deficiency is a
 key-event in the pathogenesis of PD. We propose that in order to correct this metabolic
 defect and treat PD, we need to boost neuronal NAD levels. This would improve mitochondrial
 function and could slow PD progression. Nicotinamide riboside is a precursor NAD vitamin. In
 this study we will investigate if nicotinamide riboside supplementation will correct NAD
 deficiency and thereby slow progression of PD symptoms. This study will recruit 200 patients
 with newly diagnosed PD and randomly assign them in an 1:1 ratio to either nicotinamide
 riboside or placebo administration for 52 weeks. During this trial the investigators will
 determine if nicotinamide riboside delays PD disease progression measured by clinical
 monitoring tools (MDS-UPDRS). Patients receiving nicotinamide riboside supplementation will
 receive a daily dose of 1000mg for the duration of the trial. This trial will also collect
 biological material from participants to see if nicotinamide riboside supplementation
 rectifies NAD deficiency and metabolism deficiencies.
Individuals with PD (n = 200) will be recruited starting 01/09/2019. Newly diagnosed and/or
 treatment naïve patients will be given Selegiline 10 mg/day PO and Sinemet 100 x 3. Treatment
 efficacy will be assessed upon reexamination every 1 month. If adequate symptomatic relief is
 not achieved, the dopaminergic therapy may be increased by 150 mg levodopa until optimal
 effect or a maximum dose of Sinemet 200 x 3. If adequate symptomatic relief is not achieved
 on this dose, the patient will excluded and further followed-up at the regular outpatient
 service. Once optimal effect is reached (i.e. stable treatment for at least 3 months, the
 regime will be frozen for the duration of the study period (52 weeks). Patients will then be
 randomized to receive either Nicotamide riboside or placebo. Both the participants and the
 investigators are masked. The trial will have a 52 weeks (1 year) exposure period, during
 which patients will self-administer NR 500 mg x 2/day, or placebo per os. In addition, all
 patients will take a stable regime of selegiline 10 mg/day plus optimal dopaminergic therapy.
 After the baseline visit, participants will be reassessed at 4, 13, 26, 39 and 52 weeks in
 person. Clinical evaluation will be performed by one of the neurologists involved in the
 study and/or the study nurse. The primary outcome of the study is the total score of the
 Movement disorder society Unified parkinson's disease rating scale (MDS-UPDRS) comparing the
 NR and and placebo group.
Inclusion Criteria:

 1. Have a clinical diagnosis of idiopathic PD according to the MDS clinical diagnostic
 criteria for Parkinson's disease.

 2. Positive [¹²³I]FP-CIT single photon emission CT (DaTscan) confirming nigrostriatal
 degeneration

 3. Diagnosed within one year from enrolment

 4. Hoehn and Yahr score <= 2 at enrolment

 5. Optimal symptomatic therapy, not requiring adjustments, for at least 3 months

 Exclusion Criteria:

 1. Dementia or other neurological disorder at baseline visit

 2. Metabolic, neoplastic, or other physically or mentally debilitating disorder at
 baseline visit

 3. Prior use of dopaminergic treatment