Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001419752
Ethics application status
Approved
Date submitted
28/10/2022
Date registered
7/11/2022
Date last updated
1/02/2023
Date data sharing statement initially provided
7/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effects of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) on paediatric acute-onset neuropsychiatric syndrome (PANS): An open-label study.
Scientific title
Investigating the effects of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) on gene regulation and immune dysfunction in paediatric acute-onset neuropsychiatric syndrome: An open-label study.
Secondary ID [1] 308297 0
NTIPANS1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paediatric acute-onset neuropsychiatric syndrome 328083 0
Condition category
Condition code
Neurological 325140 325140 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Full-spectrum medicinal cannabis plant extract with 0.08% THC (NTI164).

NTI164 is an oil that will be administered orally over the course of the study.

The study involves the following phases:

• Baseline/Up-titration phase: Children will receive a baseline dose of 5mg/kg/day of NTI164 that will be increased weekly by 5mg/kg for a period of 4 weeks until the maximum tolerated dose or 20mg/kg is achieved.
• Treatment phase: Children will receive the maximum tolerated dose daily or 20mg/kg/day for either an 8-week period or they may choose to extend this up to 54 weeks (Extension phase).
• Down-titration phase: At the end of the Treatment Phase, children will receive a dosage that will be gradually decreased by 5mg/kg/week for a period of 4 weeks until the end of the study.
• Extension phase: Participants who choose to continue receiving the maximum tolerated dose beyond the set 8 weeks may do so for up to 54 weeks. They will undergo the Down-titration phase at the end of their Extension phase.

The minimum participation duration time is 18 weeks and the maximum duration time is 54 weeks inclusive of the 8 week down titration phase.

Adherence to intervention will be monitored by drug product return accountability, completion of online drug administration forms and study-specific questionnaires.
Intervention code [1] 324750 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 332965 0
Any change in emotional symptoms score for RCADS-P (Revised Children's Anxiety & Depression Scale)
Timepoint [1] 332965 0
Baseline (pre-dose), 4, 12 & 16 weeks post-commencement of treatment.
Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Primary outcome [2] 333054 0
Change in Clinical Global Impression Scale -Improvement (CGI-S) This is a 7-point scale measuring symptom change from baseline.
Timepoint [2] 333054 0
Baseline (pre-dose), 4, 12 & 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [1] 415356 0
Any change in blood transcriptomic signature. Whole blood RNA sequencing to validate the immune dysfunction signature.
Timepoint [1] 415356 0
Baseline (pre-dose), 4, 12 & 16 weeks post-commencement of treatment.
Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [2] 415357 0
Any change in Yale Global Tic Severity Scale (YGTSS) scores; gold-standard for clinical measurement of tics
Timepoint [2] 415357 0
Baseline (pre-dose), 4, 12 & 16 weeks post-commencement of treatment.
Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [3] 415358 0
Any change in Children’s Yale-Brown Obsessive-Compulsive Scale scores; gold-standard for clinical measurement of OCD symptoms and severity
Timepoint [3] 415358 0
Baseline (pre-dose), 4, 12 & 16 weeks post-commencement of treatment.
Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [4] 415359 0
Any change in Conners Scale scores; gold-standard for clinical assessment of attention deficit hyperactivity disorder (ADHD) behaviours
Timepoint [4] 415359 0
Baseline (pre-dose), 4, 12 & 16 weeks post-commencement of treatment.
Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [5] 415360 0
Any change in EQ-5D-Y scores; a globally accepted tool for measuring impairment in the domains of mobility, looking after oneself (e.g. personal hygiene habits), ability to perform usual/daily activities, having pain or discomfort, and feeling worried, sad, or unhappy
Timepoint [5] 415360 0
Baseline (pre-dose), 4, 12 & 16 weeks post-commencement of treatment.
Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.

Eligibility
Key inclusion criteria
- 1 - 17 years of age
- Patients who fulfil PANS criteria
- Acute onset of OCD or severely restricted food intake
- Concurrent presentation of additional neuropsychiatric symptoms from at least 2 of the following 7 categories: anxiety, emotional lability/depression, irritability, aggression or severely oppositional behaviours, behavioural regression, deterioration in school performance, sensory or motor abnormalities (e.g. tics), somatic symptoms (e.g. sleep disturbances, enuresis or increase in urinary frequency)
- Symptoms not better explained by a known neurologic or medical disorder (e.g. Sydenham’s chorea)
- RCADS-P scores of >65 (a scale of anxiety, social phobia, panic disorder, OCD, and low mood, a score of >65 infers moderate-significant impairment)
- Other patient medications (e.g. anti-psychotics) must be stable for at least 12 weeks prior to trial participation
Minimum age
1 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Infection and/or antibiotic use in the 2 weeks prior to trial participation (i.e. baseline blood tests and commencement of NTI164)
• Recent changes to other patient medication (e.g. addition or escalation of anxiolytics, anti-depressants etc; medication dosage must be stable for at least 12 weeks prior to trial participation)
• Intellectual disability preventing adequate assent from patient, or that would affect reporting throughout trial; patients with intellectual disability must still have the capacity to verbalise their symptoms/experiences
• Ongoing immunomodulating or immunosuppressive treatment use in the previous 12 weeks, including steroids, IVIG, antibiotics, low-dose naltrexone, mycophenolate, Rituximab etc.
• Currently using or has used recreational or medicinal cannabis or cannabinoid-based medications (e.g. Sativex ®, Epidiolex ®) in the previous 12 weeks and/or is unwilling or unable to abstain for the duration of the trial
• Underlying renal impairment, cardiovascular issues (e.g. arrhythmia), current or previous thrombosis
• Impaired hepatic function, defined as serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) or total bilirubin (TBL) > 2 x ULN; this criterion can only be confirmed once baseline laboratory results are available and participants who fail this criterion will not proceed in this study
• Other diagnosed neurological condition likely to be contributing to OCD/neuropsychiatric symptoms (e.g. Huntington’s disease)

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/02/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312546 0
Commercial sector/Industry
Name [1] 312546 0
Fenix Innovation Group
Country [1] 312546 0
Australia
Funding source category [2] 312547 0
Commercial sector/Industry
Name [2] 312547 0
Neurotech International Limited
Country [2] 312547 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Fenix Innovation Group
Address
5A Hartnett Close, Mulgrave VIC Australia 3170
Country
Australia
Secondary sponsor category [1] 314148 0
None
Name [1] 314148 0
Address [1] 314148 0
Country [1] 314148 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311873 0
The Sydney Children's Hospitals Network (SCHN) Human Research Ethics Committee (HREC)
Ethics committee address [1] 311873 0
The Children’s Hospital at Westmead
Corner Hawkesbury Road and Hainsworth Street
Westmead NSW 2145
Ethics committee country [1] 311873 0
Australia
Date submitted for ethics approval [1] 311873 0
31/10/2022
Approval date [1] 311873 0
25/01/2023
Ethics approval number [1] 311873 0
Ethics committee name [2] 311874 0
Monash Health Human Research Ethics Committee
Ethics committee address [2] 311874 0
246 Clayton Road, Clayton VIC Australia 3168
Ethics committee country [2] 311874 0
Australia
Date submitted for ethics approval [2] 311874 0
01/12/2022
Approval date [2] 311874 0
Ethics approval number [2] 311874 0

Summary
Brief summary
This is an 18 to 54-week open-label study to evaluate the efficacy of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) on the severity of paediatric acute-onset neuropsychiatric syndrome (PANS) in children.

The purpose of this study is to determine how effective NTI164 is in patients with PANS when treated for 18 to 54 weeks.

Participants will commence treatment with a daily dose of 5mg/kg of NTI164. This will gradually increase over a four-week period until the maximum tolerated daily dose or 20mg/kg per day is achieved (Up-titration phase). Participants will continue to receive their respective maximum dose for eight (8) weeks (Treatment phase). Participants who wish to continue receiving their maximum tolerated dose beyond the 8-week Treatment phase may do so for up to fifty-four (54) weeks (Extension phase). At the end of the Treatment or Extension phase, participants will be gradually decreased by 5 mg/kg for a period of 4 weeks until the end of their participation (Down-titration phase).

Efficacy will be measured and monitored by performing participant- and psychologist- led questionnaires specific to measuring changes in the emotions and behaviour of patients with PANS.

Whole blood RNA sequencing will validate the immune dysfunction signature.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122678 0
Prof Russell Dale
Address 122678 0
The Children's Hospital at Westmead
Corner Hawkesbury Road and Hainsworth Street
Westmead NSW 2145
Country 122678 0
Australia
Phone 122678 0
+61 0298452006
Fax 122678 0
Email 122678 0
russell.dale@health.nsw.gov.au
Contact person for public queries
Name 122679 0
Prof Russell Dale
Address 122679 0
The Children's Hospital at Westmead
Corner Hawkesbury Road and Hainsworth Street
Westmead NSW 2145
Country 122679 0
Australia
Phone 122679 0
+61 0298452006
Fax 122679 0
Email 122679 0
russell.dale@health.nsw.gov.au
Contact person for scientific queries
Name 122680 0
Prof Russell Dale
Address 122680 0
The Children's Hospital at Westmead
Corner Hawkesbury Road and Hainsworth Street
Westmead NSW 2145
Country 122680 0
Australia
Phone 122680 0
+61 0298452006
Fax 122680 0
Email 122680 0
russell.dale@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be shared as per commercial in confidence restrictions.


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.