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

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