Clinical trial NCT05509153: A Randomised Controlled Trial, Of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers
Official title: A Randomised Controlled Trial, Of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Huntington Disease
Keywords: N-Acetylcysteine
Lead sponsor: Western Sydney Local Health District
Sponsor class: OTHER
Collaborators: name: Deakin University
name: Monash University
name: Royal Perth Hospital
name: The University of Queensland
name: University of Melbourne
First posted: 2022-08-19
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Caudate Atrophy Rate on volumetric MRI
timeFrame: Baseline through end of study (up to 3 years)
measure: Rate of motor phenoconversion
timeFrame: Baseline through end of study (up to 3 years)
Secondary outcomes:
measure: UHDRS motor subscale (total score)
timeFrame: Baseline through end of study (up to 3 years)
measure: Stroop Word
timeFrame: Baseline through end of study (up to 3 years)
measure: Trail Making Test
timeFrame: Baseline through end study (up to 3 years)
measure: Montreal Cognitive Assessment
timeFrame: Baseline through end of study (up to 3 years)
measure: Symbol Digit Modality Test
timeFrame: Baseline through end of study (up to 3 years)
measure: Changes in Mood and Behavioural symptoms
timeFrame: Baseline through end of study (up to 3 years)
measure: Changes in Daily Function
timeFrame: Baseline through end of study (up to 3 years)
measure: Change to Quality of Life
timeFrame: Baseline through end of study (up to 3 years)
measure: Study completion (Safety and Tolerability)
timeFrame: Baseline through end of study (up to 3 years)
measure: Incidence of abnormal laboratory values and/or 12-lead ECG changes (Safety and Tolerability)
timeFrame: Baseline through end of study (up to 3 years)
measure: Incidence of adverse and/or serious adverse events (Safety and Tolerability)
timeFrame: Baseline through end of study (up to 3 years)
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: The University of Queensland
state: Queensland
city: Parkdale
country: Australia
facility: Calvary Health Care Bethlehem
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Perron Institute
state: Western Australia
Study officials:
affiliation: University of Sydney
name: Clement Loy
role: PRINCIPAL_INVESTIGATOR
affiliation: Calvary Health Care Bethlehem
name: Yenni Lie
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne Health
name: Dennis Velakoulis
role: PRINCIPAL_INVESTIGATOR
affiliation: Perron Institute
name: Carolyn Orr
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Queensland
name: John O'Sullivan
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Queensland
name: Rob Adam
role: PRINCIPAL_INVESTIGATOR
References: