A Randomised Controlled Trial, Of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers

NAC-preHD is a phase II randomized placebo controlled study of oral NAC among premanifest HD gene expansion carriers, with clinical and radiological outcome at three years.

Inclusion Criteria: * Able to provide informed consent * Huntingtin gene expansion carrier with \>= 39 CAG repeats * Absence of unequivocal motor signs of HD - that is, UHDRS * Diagnostic Confidence Level needs to be \<4 upon enrolment * Expected to develop clinical HD within 10 years of trial enrolment using the Langbehn formula * Availability of an informant for corroborative history * Negative serum pregnancy test for women of childbearing potential * If of childbearing potential, is able and agrees to remain abstinent or use adequate contraceptive methods * Ability to tolerate MRI scans * Ability to tolerate blood draws * Able to comply with all study protocol requirements, according to the investigators judgement * In the opinion of the investigator, medically, psychiatrically and neurologically stable at the time of enrolment Exclusion Criteria: * Diagnosis of clinical HD * Known hypersensitivity to NAC * Pregnancy, breastfeeding or intention to do so prior to the end of the study * Exposure to any investigational drugs within 30 days of Baseline Visit * Use of supplemental NAC * Abnormalities in laboratory measurements, ECG or vital signs at screening, which precludes safe participation in the study * Current or history of substance abuse within one year of Baseline visit * Unstable psychiatric or acute medical illness including cancer, as determined by investigator * Current use of antipsychotic medications or Tetrabenazine * History of gene therapy, cell transplantation, or any experimental brain surgery * History of attempted suicide or suicidal ideation within 12 months prior to screening * Pre-existing structural brain lesion as assessed by a centrally read MRI scan during the screening period