A Randomised Controlled Trial, of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers
- Registration Number
- NCT05509153
- Lead Sponsor
- Western Sydney Local Health District
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 160
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Coated Placebo capsules, taken orally twice a day NAC NAC 1g N-Acetylcysteine capsules, taken orally twice a day.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Stroop Word Baseline through end of study (up to 3 years) Change in cognition as measured by Stroop Word
UHDRS motor subscale (total score) Baseline through end of study (up to 3 years) Measuring changes in motor function
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 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
Change to Quality of Life Baseline through end of study (up to 3 years) As measured by the standardised questionnaires, HDQoL and EQ-5D
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 Mood and Behavioural symptoms Baseline through end of study (up to 3 years) Evaluated using the PBA-s, a semi-structured interview behavioural scale
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
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
Trial Locations
- Locations (5)
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
The University of Queensland
🇦🇺Herston, Queensland, Australia
Calvary Health Care Bethlehem
🇦🇺Parkdale, Victoria, Australia
The Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Perron Institute
🇦🇺Nedlands, Western Australia, Australia