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Trial registered on ANZCTR


Registration number
ACTRN12620000949987
Ethics application status
Approved
Date submitted
18/06/2020
Date registered
23/09/2020
Date last updated
25/11/2021
Date data sharing statement initially provided
23/09/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
An Open-label, Single Arm, Pilot Study of the Feasibility of Measuring the Effect of
Intranasal Acetylcysteine on Neurometabolic Markers Using Proton Magnetic Resonance Spectroscopy
Scientific title
An Open-label, Single Arm, Pilot Study of the Feasibility of Measuring the Effect of
Intranasal Acetylcysteine on Neurometabolic Markers Using Proton Magnetic Resonance Spectroscopy
Secondary ID [1] 301504 0
Sponsor Protocol number: NN-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Traumatic Brain Injury 317837 0
Condition category
Condition code
Injuries and Accidents 315893 315893 0 0
Other injuries and accidents
Neurological 316227 316227 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intranasal N-acetylcysteine (NAC), 200mg, single dose, delivered via MAD Nasal Intranasal Mucosal Atomisation Device or Aptar CPS Nasal Pump. The intervention will be administered by trained a medical professional at the interventional site. The participants are sequentially assigned to a cohort with associated device at enrollment.
Intervention code [1] 317809 0
Treatment: Drugs
Intervention code [2] 317810 0
Treatment: Devices
Comparator / control treatment
No control – single arm open label
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324101 0
To assess the feasibility of intranasal (IN) N-acetylcysteine (NAC) administration for direct nose-to-brain delivery in healthy participants using proton magnetic resonance spectroscopy (H-MRS) assessment of change from baseline in NAC-derived metabolic markers in three brain regions of interest (dorsolateral prefrontal cortex (DLPF), occipital cortex and striatum).
Timepoint [1] 324101 0
Pre-dose, 1 hour, 3 hour and 6 hours post dose.
Secondary outcome [1] 383764 0
Safety and tolerability of a single dose of IN NAC shall be evaluated by physical and neurological assessments, vital signs, 12 lead electrocardiograms (ECGs), clinical laboratory assessments and adverse events.
Timepoint [1] 383764 0
Pre-dose, 1 hour, 3 hours, 6 hours and 7 days post dose.
Secondary outcome [2] 383765 0
To compare the time course of concentrations of NAC-derived brain metabolites (three brain regions of interest (dorsolateral prefrontal cortex (DLPF), occipital cortex and striatum) - composite outcome) with peripheral blood concentrations of NAC-derived plasma metabolites, following IN NAC administration. Plasma measurements of Glutathione (GSH), free and total NAC and GSH/ glutathione disulfide (GSSG) ratios shall be measured and compared with the H-MRS derived brain concentrations at pre-dose, 1 hour, 3 hour and 6 hour post dose.
Timepoint [2] 383765 0
Pre-dose, 1 hour, 3 hour and 6 hour post dose.

Eligibility
Key inclusion criteria
1. Healthy adult volunteers between 18 and 45 years of age, inclusive at the time of informed consent.
2. In good general health as determined by medical history, physical examination, vital signs, laboratory tests, and ECG.
3. Have a body weight in the range of 50 to 120 kg, inclusive, and a BMI of 19 to 28 kg/m2, inclusive, at Screening.
4. Agree to abstain from alcohol intake for 24 hours prior to IP administration and 24 hours prior to all other outpatient clinic visits.
5. Agree not to use prescription medications (except for birth control) within 14 days prior to IP administration and for the duration of the study, unless approved by the PI and Sponsor MM.
6. Agree not to use OTC medications and herbal medication within 14 days prior to IP administration through to the final Follow-up visit
7. Agree to refrain from participation in a competitive collision sport from the initiation of the Screening period until completion of the study (Day 28 telephone follow-up).
8. Women of Child-bearing Potential must be non-pregnant and must use an acceptable, highly effective double barrier contraception from Screening until study completion, including the follow up period.
9. Must have signed an informed consent document indicating that they understand the purpose of the study and the procedures that are required, and that they are willing to participate in the study.
10. Must be willing and able to adhere to the study visit schedule and other requirements, prohibitions and restrictions specified in this protocol.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Females who are pregnant or nursing at Screening.
2. Have a deformity of the nasal cavity, a known septum deviation; or recent (<5 years) history of surgery of the nasal cavity and/or nasopharynx.
3. History of seizures or epilepsy within the past 5 years.
4. History of moderate to severe traumatic brain injury
5. History of concussion within the past 1 year.
6. Currently have or have a history of any clinically significant medical illness or medical disorders the Investigator considers should exclude the participant
7. Psychiatric or behavioural condition which would compromise participation in the study.
8. Acute upper respiratory illness including a common cold, within 14 days prior to IP administration or have had a major illness or hospitalisation within 1 month of Screening.
9. Major or traumatic surgery within 12 weeks of Screening.
10. Any participant who plans to undergo elective surgery within 4 weeks prior to IP administration and through the end of the study including the follow-up period.
11. Positive serology test for HIV antibodies, HbsAg, or HCV antibodies at Screening.
12. Recent history (within previous 6 months) of alcohol or drug abuse.
13. Have smoked tobacco or related products within 3 months prior to dosing.
14. Have positive urine drug test at Screening and/or at any time during the study for substances of abuse
15. Have a positive alcohol breath test at Screening and/or at any time during the study.
16. Consume, on average, more than approximately 500 mg/day of caffeine (as contained in 5 cups of tea or coffee or 8 cans of soda or other caffeinated products) per day.
17. Donated blood within 60 days prior to Screening.
18. Have a history of active drug and/or food allergy or other active allergic disease requiring the constant use of medications, or a history of severe allergic reaction, angioedema or anaphylaxis.
19. Received any other experimental therapy including device or an investigational agent within 30 days or 5 half lives (whichever is longer) of IP administration.
20. Are unable to undergo MRI scanning due to the presence of non-removable metal implants, including but not limited to surgical staples, pacemaker, steel IUD etc, claustrophobia or any other contraindication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A - non-randomized, open label
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A - non-randomized, open label
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 0
Type of endpoint/s
Safety
Statistical methods / analysis
As this is an exploratory study, the sample size of this study was not determined based on a priori hypothesis testing.
In general, descriptive statistics (e.g. number of non-missing observation[n], arithmetic mean, standard deviation [SD], median, minimum and maximum) will be calculated for continuous safety data, at protocol specified time point, while frequency summary (e.g. number of observed and percentage of each categories) will be applied for categorical safety data at protocol specified time point.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
17/07/2020
Date of last participant enrolment
Anticipated
30/10/2020
Actual
6/11/2020
Date of last data collection
Anticipated
27/11/2020
Actual
3/12/2020
Sample size
Target
9
Accrual to date
Final
9
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 16894 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 30545 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 305943 0
Commercial sector/Industry
Name [1] 305943 0
Neuronasal Inc
Country [1] 305943 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services (CNS) Pty Ltd
Address
Level 2, 381 MacArthur Avenue
Hamilton, Brisbane, QLD 4007
Country
Australia
Secondary sponsor category [1] 306398 0
Commercial sector/Industry
Name [1] 306398 0
Neuronasal Australia Pty Ltd
Address [1] 306398 0
55 Gipps Street
Collingwood
VIC 3066
Country [1] 306398 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306187 0
Bellberry Limited
Ethics committee address [1] 306187 0
123 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 306187 0
Australia
Date submitted for ethics approval [1] 306187 0
20/05/2020
Approval date [1] 306187 0
30/06/2020
Ethics approval number [1] 306187 0
HREC 2020-05-436

Summary
Brief summary
Intranasal N-Acetylcysteine (NAC) is registered within Australia, but not for use in mild traumatic brain injury (concussion). This trial aims to determine if a phase 1 trial in healthy volunteers is feasible, by testing if NAC, via nose-to-brain delivery, effectively targets 3 regions of interest in the brain.

The results from this trial will be used to inform a phase 1 trial in healthy volunteers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103018 0
Dr Daniel Scherer
Address 103018 0
CMAX Clinical Research
18a North Terrace
Adelaide SA 5000
Country 103018 0
Australia
Phone 103018 0
+61870887900
Fax 103018 0
Email 103018 0
[email protected]
Contact person for public queries
Name 103019 0
Thomas Bradshaw
Address 103019 0
Neuronasal Inc
2465 Citation Street,
Wexford, PA 15090
Country 103019 0
United States of America
Phone 103019 0
+12158333080
Fax 103019 0
Email 103019 0
[email protected]
Contact person for scientific queries
Name 103020 0
Thomas Bradshaw
Address 103020 0
Neuronasal Inc
2465 Citation Street,
Wexford, PA 15090
Country 103020 0
United States of America
Phone 103020 0
+12158333080
Fax 103020 0
Email 103020 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Pilot trial and data will not be available


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.