The NAD-HD Study: A Study to Investigate Efficacy and Safety of Nicotinamide Riboside Compared With Placebo in Huntington's Disease

Inclusion Criteria:

• 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 DiagnosticConfidence Level 4 based on the Total Motor Score of the UHDRS.

• Early or mid-stage disease corresponding to Shoulson-Fahn stage 1-340 and TotalFunctional Capacity (TFC) > 2.

• Ability to walk indoors unassisted or by the help of walking aids only as determinedat screening and baseline visits.

• Ability to write and perform pen-and-paper tests (SDMT, SWRT, MoCA) and completequestionnaires (HADS-SIS, SF-12) included in the study protocol.

• Ability to follow up telephone appointments and reliably attend study visitsindependently 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 methodfor highly effective birth control throughout the study intervention period

• Capable of giving signed informed consent

Exclusion Criteria:

• Presence of other co-morbid neurological or psychiatric disorders consideredclinically significant by the investigator, including, but not limited to psychoticdisorders, brain tumor or inflammatory neurological disease.

• Attempted suicide or active suicidal ideation within 12 months prior to screening.

• A history of alcohol or substance use within a 12 month period prior to the baselinevisit, fulfilling criteria of dependence or abuse under the InternationalClassification of Diseases (ICD-10) F10-F19 (not including tobacco dependence).

• Any malignancy within 5 years prior to screening (except basal or squamous cellcarcinoma of the skin or carcinoma in situ of the cervix that has been successfullytreated) or history of a previously treated malignant disorder > 5 years prior toscreening with a remaining clinically significant recurrence risk.

• Established coronary artery disease or clinically significant cerebrovasculardisease as deemed by the investigator.

• High age-specific cardiovascular risk as defined by the NORRISK2 algorithm based onsmoking status, systolic blood pressure, serum total cholesterol and family history,modeled on the Norwegian population

• Any medical condition which, in the investigator's judgement, may preclude thesubject's safe participation in the study, interfere with the ability to comply withstudy procedures or confound the interpretation of study results.

• Use of vitamin B3 supplements in any form or dose during the study or within 3months prior to screening.

• Planned major surgery of any kind during the study period that is likely to affectclinical ratings, including, but not limited to, joint replacement and spinalsurgery.

• Electroconvulsive therapy.

• Any medical therapy with known severe side effects that, in the investigator'sjudgement, may preclude the subject's safe participation in the study, interferewith the ability to comply with study procedures or confound the interpretation ofstudy results.

• Any history of gene therapy exposure for the treatment of HD.