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

NCT05509153 | Recruiting Phase 2 DMC

• 1 other identifier: 2021/ETH12013
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 5

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.

Conditions

Huntington Disease

Keywords

N-Acetylcysteine

Outcome Measures

Primary Outcomes (2)

• Caudate Atrophy Rate on volumetric MRI

  Blinded assessment

  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

  Baseline through end of study (up to 3 years)

Secondary Outcomes (11)

• UHDRS motor subscale (total score)

  Baseline through end of study (up to 3 years)

• Stroop Word

  Baseline through end of study (up to 3 years)

• Trail Making Test

  Baseline through end study (up to 3 years)

• Montreal Cognitive Assessment

  Baseline through end of study (up to 3 years)

• Symbol Digit Modality Test

  Baseline through end of study (up to 3 years)

Study Arms (2)

NAC

EXPERIMENTAL

1g N-Acetylcysteine capsules, taken orally twice a day.

Drug: NAC

Placebo

PLACEBO COMPARATOR

Coated Placebo capsules, taken orally twice a day

Drug: Placebo

Interventions

NAC DRUG

1g of clinical grade N-Acetylcysteine capsules, taken orally twice a day

Also known as: N-Acetylcysteine

NAC

Placebo DRUG

Coated Placebo capsules, manufactured to match appearance and taste, taken orally twice a day

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Western Sydney Local Health District: lead
• Deakin University: collaborator
• Monash University: collaborator
• Royal Perth Hospital: collaborator
• The University of Queensland: collaborator
• University of Melbourne: collaborator

Study Sites (5)

Westmead Hospital

Westmead, New South Wales, 2145, Australia

RECRUITING

The University of Queensland

Herston, Queensland, 4029, Australia

NOT YET RECRUITING

Calvary Health Care Bethlehem

Parkdale, Victoria, 3195, Australia

NOT YET RECRUITING

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

NOT YET RECRUITING

Perron Institute

Nedlands, Western Australia, 6009, Australia

NOT YET RECRUITING

MeSH Terms

Conditions

Huntington Disease

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Clement Loy

  University of Sydney

  PRINCIPAL INVESTIGATOR

• Yenni Lie

  Calvary Health Care Bethlehem

  PRINCIPAL INVESTIGATOR

• Dennis Velakoulis

  Melbourne Health

  PRINCIPAL INVESTIGATOR

• Carolyn Orr

  Perron Institute

  PRINCIPAL INVESTIGATOR

• John O'Sullivan

  The University of Queensland

  PRINCIPAL INVESTIGATOR

• Rob Adam

  The University of Queensland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clement Loy

CONTACT

001164 4 8890 3560; clement.loy@sydney.edu.au

Sarah Samperi

CONTACT

001164 2 8890 9146; sarah.samperi@health.nsw.gov.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director and Neurologist, Huntington Disease Service

Model Details: 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.

Study Record Dates

• First Submitted: August 8, 2022
• First Posted: August 19, 2022
• Study Start: June 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: February 28, 2025

Record last verified: 2025-02

Locations

AU (5)