Clinical trial NCT04634136: Full-spectrum Medical Cannabis for Treatment of Spasticity in Patients With Severe Forms of Cerebral Palsy
Official title: Full-spectrum Medical Canabis Product (HemPhar) With a CBD:THC Ratio of 10:1 for Treatment of Spasticity in Children and Young Adults With Severe Forms of Cerebral Palsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Children, Adult
Spastic Cerebral Palsy
Quality of Life
Cannabis
Physical Disability
Keywords: cerebral palsy
severe spasticity
child
cannabis treatment
quality of life
young adult
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: PharmaHemp
name: University of Ljubljana, Faculty of Medicine
First posted: 2020-11-18
Enrollment: 55
Sex: ALL
Minimum age (years): 5
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Active substance: Full-spectrum medical cannabis product of CBD/THC ratio 10:1.

Arm 1: Active substance. The starting dose will be 0,08 mg THC per kilo body weight daily in 2 divided doses which will gradually be increased (escalating dose of 0,08 mg THC kg/d) until maximal dose of 1 mg/kg/d.

Arm 2: Placebo

Crossover: After 6 weeks Arm 2 will also receive the active substance and patients in both arms will continue receiving the active substance for the next 6 weeks.
Primary purpose: TREATMENT

Brief summary: The proposed study is a double-blind, placebo-controlled, cross over study on 60 children aged 5 to 25 years with severe spasticity related to cerebral palsy (CP), level IV and V with full-spectrum medical cannabis product of CBD/THC ratio 10:1.

Detailed description: Test components:

A) Active: Full-spectrum medical cannabis with ratio of CBD:THC 10:1 (HemPhar)

B) Placebo (both of the same producer)

Study Steps

1. Informed consent should be signed by parents/caregivers.
2. Weight of the participant should be determined and an IV line inserted. The following lab tests should be performed: CBC and differential counts, blood electrolytes, magnesium, calcium, phosphorus, urea \& creatinine, liver enzymes (AST, ALT, gGT)
3. ECG performed and analyzed
4. A trained physiotherapist will perform the following motor assessments: spasticity level according to modified Ashworth scale (Bohannon), function/activity assessment with the use of Gross Motor Function Measure scale (GMFM-88) and assessment of muscle power with dynamometer.
5. Randomization of patients into one of the two arms of the study
6. Active substance or placebo are introduced thereafter (as an oral oily solution for oral application) in a starting dose of 0.08 mg/kg body weight (BWt)/day divided in 2 doses (the dose is according to the THC content). The dose is gradually increased, every 3 days for 0.08 mg THC/ kg BWt/day, until the maximum dose of 1 mg THC/kg BWt/day is reached, or else until adverse effects are noted. It is expected that the average dose will be 0.33 mg/kg BWt per day.
7. The parents/caregivers are given questionnaires/scales and also given oral instructions on how to fulfil them (Edmonton scale, Borg scale and Global Impression of Change - GIC) and the paper to take down notes on possible side/adverse effects while taking the preparation (either active substance or placebo).
8. After 6 weeks of taking the substance or at the premature end of the study again the lab tests will be performed as well as the motor assessment by the physiotherapist (as above at inclusion).
9. In patients, who have been receiving placebo for the first 6 weeks, the active substance is given for the next 6 weeks, as described above (under 6). The patients who have been receiving the active substance for the first 6 weeks will continue to do so for the next 6 weeks.
10. Additional blood samples are taken at 6 weeks in both groups for analysis of levels of cannabidiol (CBD) as well as delta-9-tetrahydrocannbinol (THC) - around 4 ml of blood for determination of both levels at time(s) after ingestion: 0, 1, 2, 4, 8 and 24 hours.
11. At the end of the study (after 12 weeks) again repeat:

    1. CBC and differential counts, blood electrolytes, magnesium, calcium, phosphorus, urea \& creatinine, liver enzymes (AST, ALT, gGT)
    2. ECG
    3. Motor assessments by a physiotherapist (Ashworth/Bohannon, GMFM 88, dynamometer)
    4. Pharmacokinetics: 4 ml of blood for determination of phamacokinetics after ingestion of the last dose (as in point 10 above)
12. Evaluation of the questionnaires

NOTE: if severe side/adverse effects are noted, the test compound should be stopped immediately. If mild/moderate side/adverse effects are noted, the test component should be gradually stopped: for 0,08 mg/kg BWt/day, every 3 days.

Eligibility criteria: Inclusion criteria:

* With confirmed diagnosis of cerebral palsy (CP) and classified according to the Gross Motor Function Classification System (GMFCS) as level IV or V
* With spastic unilateral or spastic bilateral type of CP
* Those children/young adults whose parents/caregivers were informed about the aims of the study and have signed the Informed consent form

Exclusion criteria:

* Other proven diseases/conditions with the prevalence of spastic type of muscle tone (e.g. neurodegenerative, metabolic, etc.), and children with liver disease
* Other forms of CP (dyskinetic, ataxic)
* History of psychiatric illness/condition in the family

Primary outcomes:
measure: Effect on spasticity (6w; FSMC vs placebo)
timeFrame: 6 weeks
measure: Effect on Gross Motor Function Measure (6w; FSMC vs placebo)
timeFrame: 6 weeks
measure: Effect on spasticity (12w; 12w-FSMC vs 6w-FSMC)
timeFrame: 12 weeks
measure: Effect on Gross Motor Function Measure (12w; 12w-FSMC vs 6w-FSMC)
timeFrame: 12 weeks
measure: Safety and tolerability of FSMC
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: PharmaHemp
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
Study officials:
affiliation: UMC Ljubljana
name: Damjan Osredkar, MD, PhD
role: STUDY_DIRECTOR
References: