Clinical trial NCT06621888: Investigating The Effects Of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) On Paediatric Acute-onset Neuropsychiatric Syndrome (PANS)
Official title: Investigating The Effects Of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) On Paediatric Acute-onset Neuropsychiatric Syndrome (PANS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: PANS Pediatric Acute-Onset Neuropsychiatric Syndrome
Lead sponsor: Fenix Innovation Group
Sponsor class: INDUSTRY
Collaborators: name: Neurotech International Limited
First posted: 2024-10-01
Enrollment: 18
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study investigates the effectiveness of a medicinal cannabis extract (NTI164) with 0.08% THC in treating children with pediatric acute-onset neuropsychiatric syndrome (PANS) over a period of 18 to 54 weeks. Participants, aged 18 to 54, will start with a daily dose of 5mg/kg, gradually increasing to a maximum of 20mg/kg over four weeks. After reaching their maximum tolerated dose, they will maintain this dose for eight weeks, with an option to extend up to 54 weeks. The study will measure the treatment\&#39;s efficacy using questionnaires on emotional and behavioral changes, and verify the results with whole blood RNA sequencing to assess immune dysfunction.

Detailed description: This open-label study spans 18 to 54 weeks and aims to assess the efficacy of Full-Spectrum Medicinal Cannabis Plant Extract containing 0.08% THC (NTI164) for treating pediatric acute-onset neuropsychiatric syndrome (PANS) in children. The main objective is to evaluate how effective the NTI164 treatment is over the specified duration.

The study protocol involves several phases:

1. \*\*Up-titration phase:\*\* Participants will start with a daily dosage of 5 mg/kg of NTI164, incrementally increasing this dose over a four-week period until reaching either the maximum tolerated dose or 20 mg/kg per day.
2. \*\*Treatment phase:\*\* Following the up-titration, participants will continue at their maximum tolerated dose for eight weeks.
3. \*\*Extension phase:\*\* After the initial eight-week treatment phase, participants have the option to continue at their maximum dose for up to an additional 46 weeks, totaling a possible 54 weeks of treatment.
4. \*\*Down-titration phase:\*\* At the conclusion of the treatment or extension phases, the dosage will be gradually reduced by 5 mg/kg over four weeks until the participant\&#39;s involvement in the study ends.

The effectiveness of NTI164 will be monitored through both participant- and psychologist-led questionnaires, which are designed to track changes in the emotions and behavior of the patients with PANS. Additionally, the study will employ whole blood RNA sequencing as a method to validate the presence of an immune dysfunction signature, aiming to provide a biomarker for response to treatment. This comprehensive approach seeks to ensure a thorough evaluation of NTI164's potential benefits in alleviating the symptoms of PANS.

Eligibility criteria: 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 \&gt;65 (a scale of anxiety, social phobia, panic disorder, OCD, and low mood, a score of \&gt;65 infers moderate-significant impairment)
* Other patient medications (e.g. anti-psychotics) must be stable for at least 12 weeks prior to trial participation

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) \&gt; 2 x upper limit of normal (ULN) or total bilirubin (TBL) \&gt; 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)

Primary outcomes:
measure: Clinical Global Impression Scale-Improvement
timeFrame: Baseline (pre-dose), 4, 12, 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40, 52 post-commencement of treatment.
measure: Revised Childrens Anxiety and Depression Scale-Parent Version
timeFrame: 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 outcomes:
measure: Yale Global Tic Severity Scale
timeFrame: Baseline (pre-dose), 4, 12, 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40, 52 post-commencement of treatment.
measure: Children's Yale-Brown Obsessive-Compulsive Scale
timeFrame: Baseline (pre-dose), 4, 12, 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40, 52 post-commencement of treatment.
measure: Conners Scale
timeFrame: Baseline (pre-dose), 4, 12, 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40, 52 post-commencement of treatment.
measure: EQ-5D-Y
timeFrame: Baseline (pre-dose), 4, 12, 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40, 52 post-commencement of treatment.
measure: Blood Transcriptomic Signature
timeFrame: Baseline (pre-dose) and 16 weeks post-commencement of treatment.
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: The Childrens Hospital at Westmead
state: New South Wales
city: Melbourne
country: Australia
facility: Monash Children&#39;s Hospital
state: Victoria
Study officials:
References: