Tuberous Sclerosis Complex (TSC), Sanfilippo syndrome, Fragile X syndrome (FXS) MedDRA version: 20.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: HLGT Classification code 10027424 Term: Metabolic and nutritional disorders congenital System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Cannabidiol oral solution (Epidyolex)
Pharmaceutical Form: Oral solution
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use
Sponsors
Amsterdam UMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Minimum age of 6 years old. - Clinically definite diagnosis of TSC, Sanfilippo or FXS (modified Gomez criteria or positive genetic test (such as FISH test, microarray, WES-analysis)). - Suffering from severe behavioural manifestation with a minimum score of 4 on the CGI scale. - All medications or interventions for epilepsy and behavioural manifestations must have been stable dosed for one month prior to screening and the participant is willing to maintain the current regimen throughout the trial. - Presence of a consistently available patient caregiver for proxy-reports. Are the trial subjects under 18? yes Number of subjects for this age range: 18 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Use of valproate should be stable three months prior to enrolment; • Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), such as sesame oil; • Participant is currently using or has in the past used recreational or medicinal cannabis, or cannabinoid-based medications, within three months prior to screening and is unwilling to abstain for the duration of the study; • Treatment with CBD or other cannabinoid within the previous two months; • History or current evidence of significantly impaired liver function, defined as 1) Alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) > 5 × upper limit of normal (ULN); 2) ALT or AST > 3 × ULN with concomitant total bilirubin > 2.0 × ULN; or 3) ALT or AST = 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia; • Pregnancy or breastfeeding; • Glaucoma; • Participant has undergone general anaesthesia in the four weeks prior to randomization; • Use of any interfering medication within 30 days prior to enrolment or planning to take interfering medication during the trial; • Planned changes in use of anti-epileptics; • Subjects who have had changes in non-exclusionary psychotropic medications within 4 weeks of initiation of trial; • Any planned major surgery within the duration of the trial; • Expected inability to take blood samples due to anxiety or resistance.; • Unable to swallow the study drug (or placebo); • The patient is unwilling or, in the investigator’s opinion, unable to adhere to the requirements of the study; • Any condition or abnormality which may, in opinion of the investigator, compromise the safety of patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effectiveness of CBD on irritability and other behavioural problems in children and adults with TSC, Sanfilippo and FXS, and autism. ;Secondary Objective: The secondary objective is to examine the effects of CBD on aggression, hyperactivity, anxiety, mood, patient-centered outcome measures (PCOMs), disease-specific outcome measures, seizure frequency, and side effects.;Primary end point(s): To examine the effectiveness of CBD on behavioural problems using the irritability subscale of the Aberrant Behavior Checklist (ABC) in children and adults with TSC, Sanfilippo syndrome and FXS. ;Timepoint(s) of evaluation of this end point: Weekly | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To examine the effectiveness of CBD on the Behaviour problems using total ABC score in children and adults with TSC, Sanfilippo syndrome and FXS; • To examine the effectiveness of CBD on anxiety, depression and mood using the Anxiety, Depressions and Mood Scale (ADAMS) in children and adults with TSC, Sanfilippo syndrome and FXS; • To examine the effectiveness of CBD on autism symptoms using the Social Communication Questionnaire (SCQ) and Social Responsiveness Scale (SRS-2) (when applicable) in children and adults with TSC, Sanfilippo syndrome and FXS; • To examine the effectiveness of CBD on sensory processing using the Short Sensory Profile (SP-NL) (when applicable) in children and adults with TSC, Sanfilippo syndrome and FXS; • To examine the effectiveness of CBD on functional / developmental outcomes using the Goal Attainment Scaling (GAS) and Personal Questionnaire (PQ) in children and adults with TSC, Sanfilippo syndrome and FXS; • To examine the effectiveness of CBD on symptom severity and treatment response using the Clinical Global Impression (CGI) scale in children and adults with TSC, Sanfilippo syndrome and FXS; • To examine the effectiveness of CBD on parental stress using the Opvoedingsbelasting Vragenlijst (OBVL) (when applicable) in children and adults with TSC, Sanfilippo syndrome and FXS; • To examine the effectiveness of CBD on quality of life using syndrome-specific outcome measures or Pediatric Quality of Life Inventory (PedsQL) in children and adults with TSC, Sanfilippo syndrome and FXS; • To examine the effectiveness of CBD on seizure frequency using a seizure diary in children and adults with TSC, Sanfilippo syndrome and FXS. ;Timepoint(s) of evaluation of this end point: End of (interventional) periods | — |
Countries
Netherlands
Contacts
Public ContactDr A.M. van Eeghen
Amsterdam UMC
Outcome results
None listed