The NAD-HD Study: A Parallel-group, Phase 2, Double-blind Study to Investigate the Efficacy and Safety of Oral Nicotinamide Riboside Compared With Placebo in Participants Aged 18 to 80 Years With Huntington's Disease
The goal of this clinical trial is to learn if oral supplement of nicotinamide riboside (NR), a form of vitamin B3, slows disease progression in adults with Huntington's disease. It will also learn about the safety of nicotinamide riboside. The main questions it aims to answer are: * Does NR slow progression of overall symptom burden in Huntington's disease? * Does NR have an effect on any specific symptom domain in Huntington's disease? * Does supplementation with NR cause side-effects or safety issues when used for 2 years in Huntington's disease? * Does NR have an effect on selected blood, imaging, and oculomotor biomarkers in Huntington's disease? Researchers will compare NR to a placebo (a look-alike substance that contains no active compound) to see if NR works to treat Huntington's disease. Participants will: * Take 2000mg NR or a placebo every day for 2 years * Visit the clinic once every 6 months for clinical investigations and tests * Undergo brain imaging at baseline and upon completion of the study period
• Confirmed HD gene expansion carrier status with a diagnostic genetic test confirming ≥36 CAG-repeats in HTT.
• Clinically manifest HD with objective neurological signs corresponding to Diagnostic Confidence Level 4 based on the Total Motor Score of the UHDRS.
• Early or mid-stage disease corresponding to Shoulson-Fahn stage 1-340 and Total Functional Capacity (TFC) \> 2.
• Ability to walk indoors unassisted or by the help of walking aids only as determined at screening and baseline visits.
• Ability to write and perform pen-and-paper tests (SDMT, SWRT, MoCA) and complete questionnaires (HADS-SIS, SF-12) included in the study protocol.
• Ability to follow up telephone appointments and reliably attend study visits independently or with the assistance of a reliable partner (family member, friend, or assistant).
• Ability to tolerate blood draws.
• Participants who are women of childbearing potential should use an approved method for highly effective birth control throughout the study intervention period
• Capable of giving signed informed consent