Huntington DiseasePhase 2NAC-preHDNCT05509153
A Randomised Controlled Trial, Of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers
A Phase 2 study testing NAC in people with Huntington Disease, run by Western Sydney Local Health District at 5 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Huntington Disease
- What is being tested?
- NAC
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 5 sitesAustralia
- Study dates
- 1 Jun 2024to 1 May 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Australia5 sites, 5 recruiting
- Not yet recruiting
The University of Queensland
Herston, Queensland, 4029
John O'Sullivan, john.osullivan@uq.edu.au
John O'Sullivan
- Not yet recruiting
Perron Institute
Nedlands, Western Australia, 6009
Carolyn Orr, carolyn.orr@me.com
Carolyn Orr
- Not yet recruiting
Calvary Health Care Bethlehem
Parkdale, Victoria, 3195
Yenni Lie, Yenni.Lie@calvarycare.org.au
Yenni Lie
- Not yet recruiting
The Royal Melbourne Hospital
Parkville, Victoria, 3050
Dennis Velakoulis, Dennis.Velakoulis@mh.org.au
Dennis Velakoulis
- Recruiting
Westmead Hospital
Westmead, New South Wales, 2145
Clement Loy, clement.loy@sydney.edu.au
Sarah Samperi, sarah.samperi@health.nsw.gov.au
About this study
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.
- Conditions
- Huntington Disease
- Being tested
- NAC, Placebo
- Keywords
- N-Acetylcysteine
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NACDrug
Also called N-Acetylcysteine
1g of clinical grade N-Acetylcysteine capsules, taken orally twice a day
PlaceboDrug
Coated Placebo capsules, manufactured to match appearance and taste, taken orally twice a day
| Study group | Role | What they receive |
|---|---|---|
| NAC | Experimental | 1g N-Acetylcysteine capsules, taken orally twice a day. Receives: Drug: NAC |
| Placebo | Placebo comparator | Coated Placebo capsules, taken orally twice a day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Caudate Atrophy Rate on volumetric MRI
Blinded assessment
Measured: Baseline through end of study (up to 3 years)
Rate of motor phenoconversion
Defined by conversion to Diagnostic Confidence Level 4, upon blinded assessment using the UHDRS motor subscale
Measured: Baseline through end of study (up to 3 years)
Secondary outcomes (11)
UHDRS motor subscale (total score)
Measuring changes in motor function
Measured: Baseline through end of study (up to 3 years)
Stroop Word
Change in cognition as measured by Stroop Word
Measured: Baseline through end of study (up to 3 years)
Trail Making Test
Change in cognition as measured by Trail Making Test
Measured: Baseline through end study (up to 3 years)
Montreal Cognitive Assessment
Change in cognition as measured by Montreal Cognitive Assessment
Measured: Baseline through end of study (up to 3 years)
Symbol Digit Modality Test
Change in cognition as measured by Symbol Digit Modality Test
Measured: Baseline through end of study (up to 3 years)
Changes in Mood and Behavioural symptoms
Evaluated using the PBA-s, a semi-structured interview behavioural scale
Measured: Baseline through end of study (up to 3 years)
Changes in Daily Function
Measured using the Total Functional Capacity and Independent Scale from the broader UHDRS and the Functional Rating Scale for HD
Measured: Baseline through end of study (up to 3 years)
Change to Quality of Life
As measured by the standardised questionnaires, HDQoL and EQ-5D
Measured: Baseline through end of study (up to 3 years)
Study completion (Safety and Tolerability)
Measured by the proportion of participants completing NAC arm of study
Measured: Baseline through end of study (up to 3 years)
Incidence of abnormal laboratory values and/or 12-lead ECG changes (Safety and Tolerability)
Measured by the Number of participants with abnormal laboratory values and/or 12-lead ECG changes compared to baseline
Measured: Baseline through end of study (up to 3 years)
Incidence of adverse and/or serious adverse events (Safety and Tolerability)
Measured by the number of adverse and/or serious adverse events
Measured: Baseline through end of study (up to 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2022
- Study start1 Jun 2024
- Primary completion1 Nov 2026 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Western Sydney Local Health District
- Sponsor type
- University, hospital or other
- Collaborators
- Deakin University, Monash University, Royal Perth Hospital, The University of Queensland, University of Melbourne
- Responsible party
- Principal investigator, Clement Loy, Western Sydney Local Health District
- Investigators
- Clement Loy, Principal investigator, University of SydneyYenni Lie, Principal investigator, Calvary Health Care BethlehemDennis Velakoulis, Principal investigator, Melbourne HealthCarolyn Orr, Principal investigator, Perron InstituteJohn O'Sullivan, Principal investigator, The University of QueenslandRob Adam, Principal investigator, The University of Queensland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05509153
- Sponsor's protocol ID
- 2021/ETH12013
- Acronym
- NAC-preHD
- Status last verified
- Feb 2025
- First submitted
- 8 Aug 2022
- Last updated
- 28 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Currently not included in ethics approval but to be investigated.
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial, Of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers
- ClinicalTrials.gov ID
- NCT05509153
- Acronym / sponsor ID
- NAC-preHD / 2021/ETH12013
- Conditions
- Huntington Disease
- Keywords
- N-Acetylcysteine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Western Sydney Local Health DistrictUniversity, hospital or other
- Collaborators
- Deakin University, Monash University, Royal Perth Hospital, The University of Queensland, University of Melbourne
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 19 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| NAC | Experimental | Drug: NAC1g N-Acetylcysteine capsules, taken orally twice a day. |
| Placebo | Placebo comparator | Drug: PlaceboCoated Placebo capsules, taken orally twice a day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NACAlso: N-Acetylcysteine1g of clinical grade N-Acetylcysteine capsules, taken orally twice a day | Drug | NAC |
| PlaceboCoated Placebo capsules, manufactured to match appearance and taste, taken orally twice a day | Drug | Placebo |
Primary outcome
Caudate Atrophy Rate on volumetric MRI
Time frame: Baseline through end of study (up to 3 years)
Blinded assessment
Rate of motor phenoconversion
Time frame: 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
11 secondary outcomes
UHDRS motor subscale (total score)
Time frame: Baseline through end of study (up to 3 years)
Stroop Word
Time frame: Baseline through end of study (up to 3 years)
Trail Making Test
Time frame: Baseline through end study (up to 3 years)
Montreal Cognitive Assessment
Time frame: Baseline through end of study (up to 3 years)
Symbol Digit Modality Test
Time frame: Baseline through end of study (up to 3 years)
Changes in Mood and Behavioural symptoms
Time frame: Baseline through end of study (up to 3 years)
Changes in Daily Function
Time frame: Baseline through end of study (up to 3 years)
Change to Quality of Life
Time frame: Baseline through end of study (up to 3 years)
Study completion (Safety and Tolerability)
Time frame: Baseline through end of study (up to 3 years)
Incidence of abnormal laboratory values and/or 12-lead ECG changes (Safety and Tolerability)
Time frame: Baseline through end of study (up to 3 years)
Incidence of adverse and/or serious adverse events (Safety and Tolerability)
Time frame: Baseline through end of study (up to 3 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
- Individual participant dataSharing planned: Undecided. Currently not included in ethics approval but to be investigated.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Clement Loy principal investigator
University of Sydney
Yenni Lie principal investigator
Calvary Health Care Bethlehem
Dennis Velakoulis principal investigator
Melbourne Health
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NAC in people with Huntington Disease, run by Western Sydney Local Health District at 5 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clement Loy (001164 4 8890 3560, clement.loy@sydney.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Caudate Atrophy Rate on volumetric MRI (time frame: Baseline through end of study (up to 3 years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.