Clinical trial NCT01098383: Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
Official title: Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Autism
Keywords: Autism
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: The Israeli Society of Clinical Pediatrics (HIPAK)
First posted: 2010-04-02
Enrollment: 84
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: We propose a study which will combine multiple modalities in evaluating the treatment response of children with autism spectrum disorders (ASD) to acetyl-choline esterase (AChE) inhibitors and choline supplements. The primary objective of the study is to examine the efficacy of this treatment in improving core autistic symptoms. The Secondary objective of the study is to evaluate the safety and tolerability of the treatment protocol in ASD children. Exploratory objectives include evaluation of the influence of the treatment on linguistic performance, comorbid behaviors, adaptive functioning and executive functions.

Detailed description: Autism Spectrum Disorders (ASD) are a group of developmental disorders of brain function resulting in a distinct phenotype, most probably related to many specific causes. Individuals with a disorder in the autism spectrum are a heterogeneous group of patients with early childhood onset of deficits in social interaction, communication and language, and repetitive and stereotypic behaviors. ASD has become increasingly prevalent during the last few decades (Wiznitzer, 2005).

The neuro-anatomical substrate of ASD has been the subject of intense investigation, but current findings are inconclusive, limited and sometimes even contradictory.

Medical treatment of autism is still a matter of dispute. Medications used are mainly aimed to treat the comorbid symptoms, such as epilepsy, tics, obsessive-compulsive or hyperactive behaviors (Wiznitzer, 2005). Although many efforts were invested in establishing a model of autistic pathophysiology, no such model is currently accepted, and there is no evidence for an efficient treatment of the core autistic symptoms (Wiznitzer, 2005).

Previous studies indicate that many brain systems are involved in the expression of autism. Specifically, it has been suggested that autism involves neurotransmitter dysregulations (Lam et al, 2006). A recent investigation of the cholinergic system in autism, detailed below, has provided promising findings. Our study aims to assess the clinical outcomes associated with cholinergic manipulations using pharmacological agents and nutritional supplements. The study approved by the Helsinki committee for clinical research.

Eligibility criteria: Inclusion criteria:

* A formal diagnosis of Autism or Pervasive Developmental Disorder not otherwise specified (PDD-NOS), given by a child neurologist.
* Age: 10-18 years.
* A signed parental consent form.

Exclusion criteria:

* Evidence for one of the following conditions:

  * an underlying infectious disease
  * chromosomal abnormality
  * metabolic disorder
  * specific brain related disorder (such as tuberous sclerosis)
  * history of fetal cytomegalovirus infection
  * birth asphyxia
  * a history of major head injury
  * a chronic use of non-steroidal anti-inflammatory drugs, (NSAID)
  * known brain damage
* Epilepsy
* Abnormal Electro-cardiogram (ECG)
* Epileptiform EEG
* Use of psychostimulants, anti-depressants, neuroleptics or anti-convulsive agents within the past month.
* Lack of cooperation in the screening phase

Primary outcomes:
measure: Core autistic symptoms (ATEC)
timeFrame: Once every 4 weeks during the first three mounth
measure: Side effects and adverse events questionnaire
timeFrame: Once every 4 weeks during the first phase(12 weeks)
Secondary outcomes:
measure: Linguistic performance (CELF-4)
timeFrame: After 6 mounth of washout
measure: Adaptive functioning (Vineland-II)
timeFrame: After 6 mounth of washout
measure: Comorbid behaviors (CSI-4 questionnaire)
timeFrame: After 6 mouth of washout
measure: Executive functions (BRIEF questionnaire)
timeFrame: After 6 mounth of washout
Other outcomes:
Locations:
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
state: Ramat Gan
Study officials:
affiliation: Sheba Medical Center
name: Lidia Gabis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ben-Gurion University of the Negev
name: Dorit Ben-Shalom, Ph.D
role: STUDY_DIRECTOR
affiliation: Sheba Medical Center
name: Shefer Shahar, Dr.
role: STUDY_DIRECTOR
affiliation: Sheba Medical Center
name: Rotem Chayu Ben-Hur, MA
role: STUDY_DIRECTOR
References: