J012 NAD-HD: a randomized clinical trial of nicotinamide riboside in Huntington’s disease

<h3>Background</h3> Treatment aimed at increasing cellular levels of nicotinamide adenine dinucleotide (NAD) is currently emerging as a promising therapeutic strategy for several neurodegenerative disorders but has so far not been tested in Huntington’s disease (HD) patients. We present a planned phase 2 randomized controlled trial to assess the safety and efficacy of NAD replenishment therapy in HD by oral supplement of its precursor nicotinamide riboside (NR), a form of Vitamin B3. <h3>Aims</h3> The trial aims to assess whether oral supplement of 1500 mg NR twice daily improves the outcome of HD relative to placebo after 2 years of follow-up. The primary outcome will be disease progression measured as change in the composite Unified Huntington’s Disease Rating Scale. In addition, we will investigate a number of secondary and exploratory outcomes, including adverse events, caudate atrophy on MRI, and brain metabolism as measured by FDG-PET figure 1. <h3>Methods</h3> The study will recruit a total of 120 participants with manifest HD from all health regions of Norway who will be randomized to either 1500 mg NR twice daily or placebo. Follow up will be 24 months with clinical assessments and blood sampling every 6 months, and neuroimaging at baseline and 24 months. <h3>Conclusion</h3> We present the protocol of the Norwegian NAD-HD multicenter trial, which is scheduled to launch in late 2024. The trial has received funding from the Norwegian health authorities through the Norwegian Clinical Therapy Research in the Specialist Health Services program, the South-Eastern Norway Regional Health Authority, and the Dam Foundation.