Efficacy of Cannabidiol in the Management of Self-injuries in Children and Adolescents With Severe Neurodevelopmental Disorders.

Overview

Self-injuries includes repetitive actions directed at oneself, such as biting, hitting, hitting one's head or limbs, slapping oneself, pulling one's hair, or hitting oneself in the eyes, which can lead to severe injury. They are commonly reported in many neurodevelopmental disorders associated with intellectual development disorders. Faced with the difficulty of treating these self-mutilations, it seems essential to be able to explore new therapeutic avenues. Today, in the rare disease reference centers of the Necker-Enfants malades hospital, neuropathic pain in children, especially those suffering from genetic diseases with skin expression such as primary erythermalgia, is successfully and safely treated with cannabidiol in the event of failure of conventional therapies. It seems essential to be able to confirm the effectiveness of cannabidiol in treating self-injuries in children with neurodevelopmental disorders, and to help understand the mechanisms of action that underlie it. We hypothesize that the nociceptive system is involved in the occurrence of self-injuries and as a target of action of cannabidiol to treat it.

Detailed description

The objective of this project is to study the effect of cannabidiol in children with severe neurodevelopmental disorders who engage in significant self-injury, both on the frequency and severity of self-injury and on nonverbal expressions of pain. We expect a positive effect on both of these parameters, as well as a correlation between a reduction in nonverbal expressions of pain and a reduction in the frequency and severity of self-injury. If our expectations are confirmed, this would contribute to expanding the use of cannabidiol, verifying its tolerability in this patient population, and understanding the factors associated with a positive response to this unconventional treatment in order to clarify its indications.

The experimental treatment is the same for all participants. It consists of a cannabidiol (CBD) solution for oral administration: EPIDYOLEX® will be administered orally in two equal doses per day, 12 hours apart, preferably with breakfast and dinner.

Interventions

• Drug Cannabidiol
  EPIDYOLEX® will be administered orally in two equivalent doses taken 12 hours apart each day. It will be started at a dose of 5 mg/kg/day and gradually increased to 25 mg/kg/day over a titration period of 28 days. The target dose of 25 mg/kg/day will be maintained for 35 days.

Primary outcome measures

• Efficacy of cannabidiol [Time frame: Day 63]

Secondary outcome measures (12)

• Efficacy of cannabidiol [Time frame: Day 29]
• Efficacy of cannabidiol / severity of self-injuries [Time frame: Day 29]
• Efficacy of cannabidiol / severity of self-injuries [Time frame: Day 63]
• Efficacy of cannabidiol / severity of Stereotyped behaviour [Time frame: Day 29]
• Efficacy of cannabidiol / severity of Stereotyped behaviour [Time frame: Day 63]
• Efficacy of cannabidiol / frequency of Stereotyped behaviour [Time frame: Day 29]
• Efficacy of cannabidiol / frequency of Stereotyped behaviour [Time frame: Day 63]
• Efficacy of cannabidiol / severity of Aggressive/destructive behaviour [Time frame: Day 29]
• Efficacy of cannabidiol / severity of Aggressive/destructive behaviour [Time frame: Day 63]
• Efficacy of cannabidiol / frequency of Aggressive/destructive behaviour [Time frame: Day 29]
• Efficacy of cannabidiol / frequency of Aggressive/destructive behaviour [Time frame: Day 63]
• Efficacy of cannabidiol / the frequency of non-verbal expressions of pain [Time frame: Day 29]

Eligibility criteria

Inclusion criteria

• Age between 5 years and 17 years 6 months;
• Weight between 12 and 49.9 kg;
• Clinical diagnosis of severe neurodevelopmental disorder including severe to profound intellectual developmental disorder, characterized in the DSM-5 by a need for help with any daily activity (meals, dressing, toileting, elimination) and the need for constant supervision;
• Severe self-injuries during the last 7 days defined by BPI-01, i.e.:

• at least one type of self-injuries assessed as severe intensity occurring at least once every 3 hours while awake or
• at least two types of self-injuries assessed as severe intensity occurring at least once every 6 hours each while awake;
• Self-injuries refractory to treatment with atypical neuroleptic (RISPERIDONE, ARIPIPRAZOLE, etc.) at a dosage deemed effective by the investigator in view of the patient's weight, age and background, for a minimum duration of 30 days (except in the case of poor tolerance by the patient);
• No change in drug and non-drug treatments such as rehabilitative care (psychomotricity, occupational therapy, speech therapy, intervention by a specialist educator) for at least one month;
• In WOCBP and with active sexual life: negatives hCG and use of highly effective contraceptive measure until 18 days after the end of the treatment.
• The participant has a caregiver who can reliably accompany him/her to all clinic visits, provide reliable assessments, help him/her to comply with study requirements, and interact with him/her on a regular basis.
• Signature of Consent of both holders of parental authority;
• Affiliation to social security regimen.

Exclusion criteria

\- 1. Underweight corresponding to a body mass index below the IOTF 18.5 curve on the International Obesity Task Force's body mass index curves for girls and boys 2. Hypersensitivity to the active substance (cannabidiol) or to any of the excipients (refined sesame oil, anhydrous ethanol, sucralose, strawberry flavor, benzyl alcohol); 3. Treatment with or consumption of cannabidiol in the 12 weeks prior to inclusion; 4. Consumption of cannabis in the 12 weeks prior to inclusion; 5. Usual treatment (excluding treatment of self-injuries) containing molecules interacting with cannabidiol (rifampicin, carbamazepine, enzalutamide, mitotane, St. John's wort, clobazam, valproate, stiripentol, phenytoin, lamotrigine, everolimus, theophylline, tizanidine, bupropion, efavirenz, diflunisal, propofol, fenofibrate, gemfibrozil, morphine, lorazepam, repaglinide, warfarin, sirolimus, tacrolimus, digoxin); 6. Elevated transaminases > 3N or total bilirubin > 2N; 7. Known current heart failure; 8. Known current terminal renal failure (GFR < 15 ml/min/1.73 m2); 9. Known current moderate or severe hepatic insufficiency (Child-Pugh B or C); 10. Known current epilepsy or history of epilepsy, even stabilized, requiring treatment currently or not, whatever the type; 11. Pregnancy or breastfeeding; 12. Inability of the patient or entourage to comply with the study protocol; 13. Patient currently participating in another interventional research (category 1 or 2), clinical trial or clinical investigation, or who are in the exclusion period following him/her participation in another study of this type, as defined in the protocol of that study.

14\. Participant related to a person involved in the study at the investigational site

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 2 centers

• Hôpital Pitié-Salpêtrière — Paris
• Hopital Necker Enfants malades — Paris

Identifiers

NCT: NCT07564245 · APHP240090 · 2025-521161-27-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗