Full-spectrum Medical Cannabis for Treatment of Spasticity in Patients With Severe Forms of Cerebral Palsy

NCT04634136 | Completed

• 1 other identifier: 0120-162/2017/8
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (5)

• Effect on spasticity (6w; FSMC vs placebo)

  A trained physiotherapist will assess spasticity level according to modified Ashworth scale (Bohannon), which is 6-level scale for assessment of spasticity. Modified Ashworth/Bohannon Scoring Scale (Bohannon and Smith, 1987): 0 No increase in muscle tone 1. Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the range of movement (ROM ) 2. More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3. Considerable increase in muscle tone, passive movement difficult 4. Affected part(s) rigid in flexion or extension Best score is 0 (no spasticity), worst score is 4 (severe spasticity).

  6 weeks

• Effect on Gross Motor Function Measure (6w; FSMC vs placebo)

  A trained physiotherapist will assess Gross Motor Function Measure (GMFM-88) which is commonly used in the evaluation of gross motor function in children with cerebral palsy The Gross Motor Function Measure-88 (GMFM-88) is a standardized observational instrument developed to measure change in gross motor function over time. The test consists of 88 items categorized in five dimensions (Dimension A: lying and rolling, Dimension B: sitting, Dimension C: crawling and kneeling, Dimension D: standing and Dimension E: walking, running and jumping). The test was conducted as described in the GMFM-88 manual . A percentage score as compared to maximum is calculated for each dimension and for the total score of the five dimensions. Reference curves exist for GMFM-88 for each age group. Floor score is 4 (minimum score / worst), ceiling score (maximum score / best) is 75.

  6 weeks

• Effect on spasticity (12w; 12w-FSMC vs 6w-FSMC)

  A trained physiotherapist will assess spasticity level according to modified Ashworth scale (Bohannon), which is 6-level scale for assessment of spasticity Modified Ashworth/Bohannon Scoring Scale (Bohannon and Smith, 1987): 0 No increase in muscle tone 1. Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the range of movement (ROM ) 2. More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3. Considerable increase in muscle tone, passive movement difficult 4. Affected part(s) rigid in flexion or extension Best score is 0 (no spasticity), worst score is 4 (severe spasticity).

  12 weeks

• Effect on Gross Motor Function Measure (12w; 12w-FSMC vs 6w-FSMC)

  A trained physiotherapist will assess Gross Motor Function Measure (GMFM-88) which is commonly used in the evaluation of gross motor function in children with cerebral palsy. The Gross Motor Function Measure-88 (GMFM-88) is a standardized observational instrument developed to measure change in gross motor function over time. The test consists of 88 items categorized in five dimensions (Dimension A: lying and rolling, Dimension B: sitting, Dimension C: crawling and kneeling, Dimension D: standing and Dimension E: walking, running and jumping). The test was conducted as described in the GMFM-88 manual . A percentage score as compared to maximum is calculated for each dimension and for the total score of the five dimensions. Reference curves exist for GMFM-88 for each age group. Floor score is 4 (minimum score / worst), ceiling score (maximum score / best) is 75.

  12 weeks

• Safety and tolerability of FSMC

  Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\]

  12 weeks

Study Arms (2)

Active Substance: Full-spectrum Medical Canabis Product (HemPhar)

ACTIVE COMPARATOR

For research purposes the investigators will use a preparation in the form of drops, containing full-spectrum medical cannabis extract (HemPhar) with THC:CBD ratio 1:10, and other cannabinoids as well, provided by Pharmahemp, GMP-certified medical cannabis producer.

Diagnostic Test: Lab tests; Diagnostic Test: ECG; Diagnostic Test: Cannabinoid Levels; Drug: Full-spectrum Medical Canabis Product (HemPhar); Diagnostic Test: Spasticity level according to modified Ashworth scale (Bohannon); Diagnostic Test: Gross Motor Function Measure; Diagnostic Test: Borg rating of perceived exertion scale; Diagnostic Test: Edmonton symptom assessment system

Placebo

PLACEBO COMPARATOR

For research purposes the investigators will use a placebo in the form of drops, containing oil only, provided by Pharmahemp, GMP-certified medical cannabis producer.

Diagnostic Test: Lab tests; Diagnostic Test: ECG; Drug: Placebo; Diagnostic Test: Spasticity level according to modified Ashworth scale (Bohannon); Diagnostic Test: Gross Motor Function Measure; Diagnostic Test: Borg rating of perceived exertion scale; Diagnostic Test: Edmonton symptom assessment system

Interventions

Lab tests DIAGNOSTIC_TEST

CBC and differential counts, blood electrolytes, magnesium, calcium, phosphorus, urea \& creatinine, liver enzymes (AST, ALT, gGT)

Also known as: Basic hematology and biochemistry

Active Substance: Full-spectrum Medical Canabis Product (HemPhar); Placebo

ECG DIAGNOSTIC_TEST

Electrocardiogram

Active Substance: Full-spectrum Medical Canabis Product (HemPhar); Placebo

Cannabinoid Levels DIAGNOSTIC_TEST

Determination of levels of cannabidiol (CBD) and delta-9-tetrahydrocannbinol (THC) for determination of levels at following time(s) after ingestion: 0, 1, 2, 4, 8 and 24 hours.

Also known as: Pharmacokinetics of cannabinoids

Active Substance: Full-spectrum Medical Canabis Product (HemPhar)

Full-spectrum Medical Canabis Product (HemPhar) DRUG

Active substance

Also known as: Active substance

Active Substance: Full-spectrum Medical Canabis Product (HemPhar)

Placebo DRUG

Placebo

Placebo

Spasticity level according to modified Ashworth scale (Bohannon) DIAGNOSTIC_TEST

A trained physiotherapist will assess spasticity level according to modified Ashworth scale (Bohannon), which is 6-level scale for assessment of spasticity. Modified Ashworth/Bohannon Scoring Scale (Bohannon and Smith, 1987): 0 No increase in muscle tone 1. Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the range of movement (ROM ) 2. More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3. Considerable increase in muscle tone, passive movement difficult 4. Affected part(s) rigid in flexion or extension Best score is 0 (no spasticity), worst score is 4 (severe spasticity).

Active Substance: Full-spectrum Medical Canabis Product (HemPhar); Placebo

Gross Motor Function Measure DIAGNOSTIC_TEST

A trained physiotherapist will assess Gross Motor Function Measure (GMFM-88) which is commonly used in the evaluation of gross motor function in children with cerebral palsy The Gross Motor Function Measure-88 (GMFM-88) is a standardized observational instrument developed to measure change in gross motor function over time. The test consists of 88 items categorized in five dimensions (Dimension A: lying and rolling, Dimension B: sitting, Dimension C: crawling and kneeling, Dimension D: standing and Dimension E: walking, running and jumping). The test was conducted as described in the GMFM-88 manual . A percentage score as compared to maximum is calculated for each dimension and for the total score of the five dimensions. Reference curves exist for GMFM-88 for each age group. Floor score is 4 (minimum score / worst), ceiling score (maximum score / best) is 75.

Active Substance: Full-spectrum Medical Canabis Product (HemPhar); Placebo

Borg rating of perceived exertion scale DIAGNOSTIC_TEST

Borg rating of perceived exertion scale

Active Substance: Full-spectrum Medical Canabis Product (HemPhar); Placebo

Edmonton symptom assessment system DIAGNOSTIC_TEST

Edmonton symptom assessment system and general impression scale (1 - very much improved; 7 - very much worse).

Active Substance: Full-spectrum Medical Canabis Product (HemPhar); Placebo

Eligibility Criteria

• Age: 5 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead
• PharmaHemp: collaborator
• University of Ljubljana, Faculty of Medicine: collaborator

Study Sites (2)

PharmaHemp

Ljubljana, 1000, Slovenia

Location

University Medical Centre Ljubljana

Ljubljana, Slovenia

Location

MeSH Terms

Conditions

Cerebral Palsy; Marijuana Abuse; Muscle Spasticity

Interventions

Electrocardiography; compact-colony-forming active substance

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Study Officials

• Damjan Osredkar, MD, PhD

  UMC Ljubljana

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo product will be of the same quantity and apperance (same packaging) as the active substance. All partricipants will be blinded to relevant patient data.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: November 18, 2020
• Study Start: October 15, 2020
• Primary Completion: December 1, 2023
• Study Completion: February 29, 2024
• Last Updated: May 22, 2024

Record last verified: 2023-05

Locations

SL (2)