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

Primary Purpose

Huntington Disease

Status
Not yet recruiting
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
NAC
Placebo
Sponsored by
Western Sydney Local Health District
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Huntington Disease focused on measuring N-Acetylcysteine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Westmead Hospital
  • The University of Queensland
  • Calvary Health Care Bethlehem
  • The Royal Melbourne Hospital
  • Perron Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

NAC

Placebo

Arm Description

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

Coated Placebo capsules, taken orally twice a day

Outcomes

Primary Outcome Measures

Caudate Atrophy Rate on volumetric MRI
Blinded assessment
Rate of motor phenoconversion
Defined by conversion to Diagnostic Confidence Level 4, upon blinded assessment using the UHDRS motor subscale

Secondary Outcome Measures

UHDRS motor subscale (total score)
Measuring changes in motor function
Stroop Word
Change in cognition as measured by Stroop Word
Trail Making Test
Change in cognition as measured by Trail Making Test
Montreal Cognitive Assessment
Change in cognition as measured by Montreal Cognitive Assessment
Symbol Digit Modality Test
Change in cognition as measured by Symbol Digit Modality Test
Changes in Mood and Behavioural symptoms
Evaluated using the PBA-s, a semi-structured interview behavioural scale
Changes in Daily Function
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
As measured by the standardised questionnaires, HDQoL and EQ-5D
Study completion (Safety and Tolerability)
Measured by the proportion of participants completing NAC arm of study
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
Incidence of adverse and/or serious adverse events (Safety and Tolerability)
Measured by the number of adverse and/or serious adverse events

Full Information

First Posted
August 8, 2022
Last Updated
August 21, 2022
Sponsor
Western Sydney Local Health District
Collaborators
Deakin University, Monash University, Royal Perth Hospital, The University of Queensland, University of Sydney, University of Melbourne
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1. Study Identification

Unique Protocol Identification Number
NCT05509153
Brief Title
A Randomised Controlled Trial, Of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers
Acronym
NAC-preHD
Official Title
A Randomised Controlled Trial, Of N-Acetyl Cysteine (NAC), for Premanifest Huntingtin Gene Expansion Carriers
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2022 (Anticipated)
Primary Completion Date
November 1, 2026 (Anticipated)
Study Completion Date
May 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Western Sydney Local Health District
Collaborators
Deakin University, Monash University, Royal Perth Hospital, The University of Queensland, University of Sydney, University of Melbourne

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington Disease
Keywords
N-Acetylcysteine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NAC
Arm Type
Experimental
Arm Description
1g N-Acetylcysteine capsules, taken orally twice a day.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Coated Placebo capsules, taken orally twice a day
Intervention Type
Drug
Intervention Name(s)
NAC
Other Intervention Name(s)
N-Acetylcysteine
Intervention Description
1g of clinical grade N-Acetylcysteine capsules, taken orally twice a day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Coated Placebo capsules, manufactured to match appearance and taste, taken orally twice a day
Primary Outcome Measure Information:
Title
Caudate Atrophy Rate on volumetric MRI
Description
Blinded assessment
Time Frame
Baseline through end of study (up to 3 years)
Title
Rate of motor phenoconversion
Description
Defined by conversion to Diagnostic Confidence Level 4, upon blinded assessment using the UHDRS motor subscale
Time Frame
Baseline through end of study (up to 3 years)
Secondary Outcome Measure Information:
Title
UHDRS motor subscale (total score)
Description
Measuring changes in motor function
Time Frame
Baseline through end of study (up to 3 years)
Title
Stroop Word
Description
Change in cognition as measured by Stroop Word
Time Frame
Baseline through end of study (up to 3 years)
Title
Trail Making Test
Description
Change in cognition as measured by Trail Making Test
Time Frame
Baseline through end study (up to 3 years)
Title
Montreal Cognitive Assessment
Description
Change in cognition as measured by Montreal Cognitive Assessment
Time Frame
Baseline through end of study (up to 3 years)
Title
Symbol Digit Modality Test
Description
Change in cognition as measured by Symbol Digit Modality Test
Time Frame
Baseline through end of study (up to 3 years)
Title
Changes in Mood and Behavioural symptoms
Description
Evaluated using the PBA-s, a semi-structured interview behavioural scale
Time Frame
Baseline through end of study (up to 3 years)
Title
Changes in Daily Function
Description
Measured using the Total Functional Capacity and Independent Scale from the broader UHDRS and the Functional Rating Scale for HD
Time Frame
Baseline through end of study (up to 3 years)
Title
Change to Quality of Life
Description
As measured by the standardised questionnaires, HDQoL and EQ-5D
Time Frame
Baseline through end of study (up to 3 years)
Title
Study completion (Safety and Tolerability)
Description
Measured by the proportion of participants completing NAC arm of study
Time Frame
Baseline through end of study (up to 3 years)
Title
Incidence of abnormal laboratory values and/or 12-lead ECG changes (Safety and Tolerability)
Description
Measured by the Number of participants with abnormal laboratory values and/or 12-lead ECG changes compared to baseline
Time Frame
Baseline through end of study (up to 3 years)
Title
Incidence of adverse and/or serious adverse events (Safety and Tolerability)
Description
Measured by the number of adverse and/or serious adverse events
Time Frame
Baseline through end of study (up to 3 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clement Loy
Phone
001164 4 8890 3560
Email
clement.loy@sydney.edu.au
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Samperi
Phone
001164 2 8890 9146
Email
sarah.samperi@health.nsw.gov.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clement Loy
Organizational Affiliation
University of Sydney
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yenni Lie
Organizational Affiliation
Calvary Health Care Bethlehem
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dennis Velakoulis
Organizational Affiliation
Melbourne Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Carolyn Orr
Organizational Affiliation
Perron Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John O'Sullivan
Organizational Affiliation
The University of Queensland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rob Adam
Organizational Affiliation
The University of Queensland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clement Loy
Email
clement.loy@sydney.edu.au
First Name & Middle Initial & Last Name & Degree
Sarah Samperi
Email
sarah.samperi@health.nsw.gov.au
First Name & Middle Initial & Last Name & Degree
Clement Loy
Facility Name
The University of Queensland
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John O'Sullivan
Email
john.osullivan@uq.edu.au
First Name & Middle Initial & Last Name & Degree
John O'Sullivan
First Name & Middle Initial & Last Name & Degree
Rob Adam
Facility Name
Calvary Health Care Bethlehem
City
Parkdale
State/Province
Victoria
ZIP/Postal Code
3195
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yenni Lie
Email
Yenni.Lie@calvarycare.org.au
First Name & Middle Initial & Last Name & Degree
Yenni Lie
Facility Name
The Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Perron Institute
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolyn Orr
Email
carolyn.orr@me.com
First Name & Middle Initial & Last Name & Degree
Carolyn Orr

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Currently not included in ethics approval but to be investigated.

Learn more about this trial

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

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