Huntington Disease
Conditions
Keywords
N-Acetylcysteine
Brief summary
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.
Interventions
DRUGNAC
1g of clinical grade N-Acetylcysteine capsules, taken orally twice a day
DRUGPlacebo
Coated Placebo capsules, manufactured to match appearance and taste, taken orally twice a day
Sponsors
Deakin University
Monash University
Royal Perth Hospital
The University of Queensland
University of Melbourne
Western Sydney Local Health District
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants will be randomly allocated to either the NAC arm or the placebo arm using Block Randomisation, stratified by site, through a centralised process, with allocation concealment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Caudate Atrophy Rate on volumetric MRI | Baseline through end of study (up to 3 years) | Blinded assessment |
| Rate of motor phenoconversion | Baseline through end of study (up to 3 years) | Defined by conversion to Diagnostic Confidence Level 4, upon blinded assessment using the UHDRS motor subscale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trail Making Test | Baseline through end study (up to 3 years) | Change in cognition as measured by Trail Making Test |
| Montreal Cognitive Assessment | Baseline through end of study (up to 3 years) | Change in cognition as measured by Montreal Cognitive Assessment |
| Symbol Digit Modality Test | Baseline through end of study (up to 3 years) | Change in cognition as measured by Symbol Digit Modality Test |
| Changes in Mood and Behavioural symptoms | Baseline through end of study (up to 3 years) | Evaluated using the PBA-s, a semi-structured interview behavioural scale |
| UHDRS motor subscale (total score) | Baseline through end of study (up to 3 years) | Measuring changes in motor function |
| Change to Quality of Life | Baseline through end of study (up to 3 years) | As measured by the standardised questionnaires, HDQoL and EQ-5D |
| Study completion (Safety and Tolerability) | Baseline through end of study (up to 3 years) | Measured by the proportion of participants completing NAC arm of study |
| Incidence of abnormal laboratory values and/or 12-lead ECG changes (Safety and Tolerability) | Baseline through end of study (up to 3 years) | Measured by the Number of participants with abnormal laboratory values and/or 12-lead ECG changes compared to baseline |
| Incidence of adverse and/or serious adverse events (Safety and Tolerability) | Baseline through end of study (up to 3 years) | Measured by the number of adverse and/or serious adverse events |
| Changes in Daily Function | Baseline through end of study (up to 3 years) | Measured using the Total Functional Capacity and Independent Scale from the broader UHDRS and the Functional Rating Scale for HD |
| Stroop Word | Baseline through end of study (up to 3 years) | Change in cognition as measured by Stroop Word |
Countries
Australia
Contacts
Primary ContactClement Loy
Backup ContactSarah Samperi
Outcome results
None listed