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

Huntington Disease Clinical Trial

— NAC-preHD  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05509153
• Other study ID #: 2021/ETH12013
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 1, 2022
• Est. completion date: May 1, 2027

Study information

• Verified date: August 2022
• Source: Western Sydney Local Health District
• Contact: Clement Loy
• Phone: 001164 4 8890 3560
• Email: clement.loy[@]sydney.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: May 1, 2027
• Est. primary completion date: November 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Drug:
• NAC
1g of clinical grade N-Acetylcysteine capsules, taken orally twice a day
• Placebo
Coated Placebo capsules, manufactured to match appearance and taste, taken orally twice a day

Locations

Country	Name	City	State
Australia	The University of Queensland	Herston	Queensland
Australia	Perron Institute	Nedlands	Western Australia
Australia	Calvary Health Care Bethlehem	Parkdale	Victoria
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Westmead Hospital	Westmead	New South Wales

Sponsors (7)

Lead Sponsor	Collaborator
Western Sydney Local Health District	Deakin University, Monash University, Royal Perth Hospital, The University of Queensland, University of Melbourne, University of Sydney

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Caudate Atrophy Rate on volumetric MRI	Blinded assessment	Baseline through end of study (up to 3 years)
Primary	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	UHDRS motor subscale (total score)	Measuring changes in motor function	Baseline through end of study (up to 3 years)
Secondary	Stroop Word	Change in cognition as measured by Stroop Word	Baseline through end of study (up to 3 years)
Secondary	Trail Making Test	Change in cognition as measured by Trail Making Test	Baseline through end study (up to 3 years)
Secondary	Montreal Cognitive Assessment	Change in cognition as measured by Montreal Cognitive Assessment	Baseline through end of study (up to 3 years)
Secondary	Symbol Digit Modality Test	Change in cognition as measured by Symbol Digit Modality Test	Baseline through end of study (up to 3 years)
Secondary	Changes in Mood and Behavioural symptoms	Evaluated using the PBA-s, a semi-structured interview behavioural scale	Baseline through end of study (up to 3 years)
Secondary	Changes in Daily Function	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)
Secondary	Change to Quality of Life	As measured by the standardised questionnaires, HDQoL and EQ-5D	Baseline through end of study (up to 3 years)
Secondary	Study completion (Safety and Tolerability)	Measured by the proportion of participants completing NAC arm of study	Baseline through end of study (up to 3 years)
Secondary	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	Baseline through end of study (up to 3 years)
Secondary	Incidence of adverse and/or serious adverse events (Safety and Tolerability)	Measured by the number of adverse and/or serious adverse events	Baseline through end of study (up to 3 years)