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Cannabidiol (Epidyolex®) for severe behavioral manifestations in patients with tuberous sclerosis complex, mucopolysaccharidosis type III and fragile X syndrome: protocol for a series of randomized, placebo-controlled N-of-1 trials.
Müller, A R; den Hollander, B; van de Ven, P M; Roes, K C B; Geertjens, L; Bruining, H; van Karnebeek, C D M; Jansen, F E; de Wit, M C Y; Ten Hoopen, L W; Rietman, A B; Dierckx, B; Wijburg, F A; Boot, E; Brands, M M G; van Eeghen, A M.
Afiliação
  • Müller AR; Department of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
  • den Hollander B; 's Heeren Loo Care Group, Amersfoort, The Netherlands.
  • van de Ven PM; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, the Netherlands.
  • Roes KCB; Department of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
  • Geertjens L; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, the Netherlands.
  • Bruining H; United for Metabolic Diseases, Amsterdam, The Netherlands.
  • van Karnebeek CDM; Department of Data Science and Biostatistics, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Jansen FE; Department of Health Evidence, Biostatistics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • de Wit MCY; Child and Adolescent Psychiatry and Psychosocial Care, Amsterdam UMC Location Vrije Universiteit, Amsterdam, The Netherlands.
  • Ten Hoopen LW; Amsterdam UMC, Amsterdam Neuroscience, Amsterdam Reproduction and Development, N=You Neurodevelopmental Precision Center, Amsterdam, The Netherlands.
  • Rietman AB; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, the Netherlands.
  • Dierckx B; Child and Adolescent Psychiatry and Psychosocial Care, Amsterdam UMC Location Vrije Universiteit, Amsterdam, The Netherlands.
  • Wijburg FA; Amsterdam UMC, Amsterdam Neuroscience, Amsterdam Reproduction and Development, N=You Neurodevelopmental Precision Center, Amsterdam, The Netherlands.
  • Boot E; Levvel, Center for Child and Adolescent Psychiatry, Amsterdam, The Netherlands.
  • Brands MMG; Department of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
  • van Eeghen AM; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, the Netherlands.
BMC Psychiatry ; 24(1): 23, 2024 01 04.
Article em En | MEDLINE | ID: mdl-38177999
ABSTRACT

BACKGROUND:

Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design.

METHODS:

We aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N-of-1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants' natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N-of-1 trials.

DISCUSSION:

These N-of-1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level. TRIAL REGISTRATION EudraCT 2021-003250-23, registered 25 August 2022, https//www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL .
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Tuberosa / Canabidiol / Mucopolissacaridoses / Transtorno do Espectro Autista / Síndrome do Cromossomo X Frágil Tipo de estudo: Clinical_trials Limite: Humans Idioma: En Revista: BMC Psychiatry Assunto da revista: PSIQUIATRIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Tuberosa / Canabidiol / Mucopolissacaridoses / Transtorno do Espectro Autista / Síndrome do Cromossomo X Frágil Tipo de estudo: Clinical_trials Limite: Humans Idioma: En Revista: BMC Psychiatry Assunto da revista: PSIQUIATRIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda