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

February 25, 2025 updated by: Clement Loy, Western Sydney Local Health District
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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Not yet recruiting
        • The University of Queensland
        • Contact:
        • Contact:
          • John O'Sullivan
        • Contact:
          • Rob Adam
    • Victoria
      • Parkdale, Victoria, Australia, 3195
      • Parkville, Victoria, Australia, 3050
        • Not yet recruiting
        • The Royal Melbourne Hospital
        • Contact:
        • Contact:
          • Dennis Velakoulis
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Not yet recruiting
        • Perron Institute
        • Contact:
        • Contact:
          • Carolyn Orr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NAC
1g N-Acetylcysteine capsules, taken orally twice a day.
Drug: NAC
1g of clinical grade N-Acetylcysteine capsules, taken orally twice a day
Other Names:
  • N-Acetylcysteine
Placebo Comparator: Placebo
Coated Placebo capsules, taken orally twice a day
Drug: Placebo
Coated Placebo capsules, manufactured to match appearance and taste, taken orally twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Caudate Atrophy Rate on volumetric MRI
Time Frame: Baseline through end of study (up to 3 years)
Blinded assessment
Baseline through end of study (up to 3 years)
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
Baseline through end of study (up to 3 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
UHDRS motor subscale (total score)
Time Frame: Baseline through end of study (up to 3 years)
Measuring changes in motor function
Baseline through end of study (up to 3 years)
Stroop Word
Time Frame: Baseline through end of study (up to 3 years)
Change in cognition as measured by Stroop Word
Baseline through end of study (up to 3 years)
Trail Making Test
Time Frame: Baseline through end study (up to 3 years)
Change in cognition as measured by Trail Making Test
Baseline through end study (up to 3 years)
Montreal Cognitive Assessment
Time Frame: Baseline through end of study (up to 3 years)
Change in cognition as measured by Montreal Cognitive Assessment
Baseline through end of study (up to 3 years)
Symbol Digit Modality Test
Time Frame: Baseline through end of study (up to 3 years)
Change in cognition as measured by Symbol Digit Modality Test
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)
Evaluated using the PBA-s, a semi-structured interview behavioural scale
Baseline through end of study (up to 3 years)
Changes in Daily Function
Time Frame: 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
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)
As measured by the standardised questionnaires, HDQoL and EQ-5D
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)
Measured by the proportion of participants completing NAC arm of study
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)
Measured by the Number of participants with abnormal laboratory values and/or 12-lead ECG changes compared to baseline
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)
Measured by the number of adverse and/or serious adverse events
Baseline through end of study (up to 3 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Western Sydney Local Health District

Collaborators

Monash University
University of Melbourne
The University of Queensland
Royal Perth Hospital
Deakin University

Investigators

  • Principal Investigator: 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2024

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

August 8, 2022

First Submitted That Met QC Criteria

August 18, 2022

First Posted (Actual)

August 19, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 25, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021/ETH12013

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Currently not included in ethics approval but to be investigated.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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