Behavioral Therapy for Cornelia de Lange Syndrome

Overseen By Michelle D Chin, MS, MPH

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Disqualifiers: Severe SIB, Uncontrolled seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 days

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The goals of this clinical trial are to identify factors associated with the development of problem behavior in Cornelia de Lange syndrome (CdLS) and to develop an effective behavioral assessment and treatment model for problem behavior in children with CdLS. The hypotheses are as follows: 1. Based on pilot data, the investigators hypothesize that individuals with CdLS will exhibit preferences for auditory stimuli relative to other categories (e.g., visual, tactile) of stimuli. 2. Based on pilot data, the investigators hypothesize that individuals with CdLS will exhibit problem behavior to obtain adult attention or to escape task demands relative to tangible and control conditions, as measured by functional analysis results. 3. Function-based behavioral treatments will reduce problem behavior in individuals with CdLS by 80% or greater relative to baseline rates. 4. Individuals with CdLS and problem behavior will exhibit more impaired communication, demonstrate increased emotion dysregulation, and exhibit more severe symptoms of Autism Spectrum Disorder (ASD) relative to those with CdLS and no problem behavior. Participants in the intervention group (families of children with CdLS and problem behaviors) will be asked to complete study measures and attend 2 full days and one half-day of clinic services at Kennedy Krieger Institute so that the study team can provide assessment and treatment of child problem behaviors, and then train parents to apply the intervention. Participants in the control group (families of children with CdLS and no problem behavior) will be asked to complete study measures once every 3 months for a 2-year period to monitor the children. This study will improve the ability to effectively treat problem behavior is CdLS, as well as identify key variables associated with problem behavior in CdLS which may be examined in future studies and clinical practice to foster early intervention and prevention efforts.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of this treatment for Cornelia de Lange Syndrome?

While there is no direct evidence from the provided research about the effectiveness of ABA-based therapy for Cornelia de Lange Syndrome, ABA therapy has been shown to be effective in managing similar behavioral issues in other conditions, such as autism spectrum disorders, which share some behavioral characteristics with Cornelia de Lange Syndrome. ^{1 2 3 4 5}

Is behavioral therapy, like ABA, safe for people with developmental disabilities?

The research does not specifically address safety concerns for ABA therapy, but it is widely used for various developmental disabilities, suggesting it is generally considered safe. However, always consult with a healthcare provider for personalized advice. ^{6 7 8 9 10}

How does ABA-based functional analysis and treatment differ from other treatments for Cornelia de Lange Syndrome?

ABA-based functional analysis and treatment is unique because it focuses on understanding and modifying behavior through structured interventions, such as identifying the reasons behind problem behaviors and teaching alternative communication methods. This approach is different from other treatments that may not specifically target the behavioral aspects of Cornelia de Lange Syndrome. ^{7 11 12 13 14}

Research Team

Patricia F Kurtz, PhD

Principal Investigator

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Eligibility Criteria

This trial is for English-speaking parents of children aged 3-15 with Cornelia de Lange syndrome (CdLS). It includes those whose children exhibit self-injurious behavior, aggression, or disruptive behavior and can attend clinic visits. Children without these behaviors are in the control group.

Inclusion Criteria

I am an English-speaking parent of a child with CdLS and willing to complete study measures.

I am an English-speaking parent of a child with CdLS, willing to attend clinic visits, complete study tasks, and follow a behavior plan.

Exclusion Criteria

Children with CdLS in the treatment group should not show certain behaviors, be younger than 3 or older than 15, or require extensive medical care that could affect participation. Also, parents of these children should be willing to complete study procedures and be able to speak English.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Visit Assessments

Parents complete research measures at home and participate in phone interviews to assess child behavior and preferences.

2-4 weeks

Remote assessments and phone interviews

Treatment

Participants attend clinic services for assessment and treatment of problem behaviors, including functional analysis and parent training.

2 days

2 full days and one half-day at Kennedy Krieger Institute

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits and phone calls.

12 weeks

Follow-up phone calls at 1, 4, 8, and 12 weeks post-treatment

Long-term Monitoring (Control Group)

Control group participants are monitored every 3 months for up to 2 years to track the emergence of problem behavior.

2 years

Quarterly monitoring

Treatment Details

Interventions

• ABA-based functional analysis and treatment

Trial Overview The study tests a behavioral assessment and treatment based on Applied Behavior Analysis (ABA) for managing problem behaviors in kids with CdLS. The goal is to reduce such behaviors by at least 80% using function-based treatments.

Participant Groups

Group I: ABA-based functional analysis and treatment Experimental Treatment 1 Intervention

Assessment and Treatment for problem behavior exhibited by children with CdLS

Group II: No Problem behavior Control Group Active Control 1 Intervention

Quarterly Monitoring of children with CdLS that do not exhibit problem behavior

ABA-based functional analysis and treatment is already approved in United States, European Union, Canada for the following indications:

Approved in United States as ABA Therapy for:

• Autism Spectrum Disorder (ASD)
• Behavioral Disorders
• Developmental Disabilities

Approved in European Union as ABA Therapy for:

• Autism Spectrum Disorder (ASD)
• Behavioral Disorders
• Developmental Disabilities

Approved in Canada as ABA Therapy for:

• Autism Spectrum Disorder (ASD)
• Behavioral Disorders
• Developmental Disabilities

Who Is Running the Clinical Trial?

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Lead Sponsor

Trials

93

Recruited

25,200+

Findings from Research

In a study of 49 individuals with Cornelia de Lange syndrome, a significant number exhibited behavioral challenges, including sleep disturbances (55%), daily aggression (49%), and self-injury (44%), highlighting the need for tailored support.

The presence of these behavioral issues correlated with the severity of mental retardation and the occurrence of autistic-like symptoms, indicating that the degree of cognitive impairment may influence the behavioral phenotype and support requirements throughout life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioural phenotype of Cornelia de Lange syndrome. Berney, TP., Ireland, M., Burn, J.[2022]

In a 7-year follow-up study of 30 individuals with Cornelia de Lange syndrome, there was an observed increase in the proportion of individuals meeting criteria for autism spectrum disorder, indicating complex changes in behavior over time.

Despite these behavioral changes, both Cornelia de Lange and Cri du Chat syndrome groups showed stable levels of adaptive ability and improvements in receptive language, suggesting that overall abilities did not decline during the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age-related Behavioural Change in Cornelia de Lange and Cri du Chat Syndromes: A Seven Year Follow-up Study. Cochran, L., Welham, A., Oliver, C., et al.[2023]

In a study of 56 individuals with Cornelia de Lange Syndrome (CdLS), common behavioral characteristics such as hyperactivity, anxiety, and autistic-like features were identified, highlighting the complexity of the syndrome's behavioral profile.

The variability in behavioral traits was linked to clinical factors like age and cognitive level, suggesting that CdLS may encompass multiple behavioral phenotypes that differ significantly among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The behavioural phenotype of Cornelia de Lange Syndrome: a study of 56 individuals. Basile, E., Villa, L., Selicorni, A., et al.[2015]

Individuals with Cornelia de Lange syndrome (CdLS) exhibit a behavioral phenotype characterized by prominent autistic traits, particularly repetitive behaviors and self-injurious behaviors, which significantly affect their quality of life.

There is a need for targeted treatment approaches to manage these repetitive and self-injurious behaviors in CdLS, as they differ from typical autism and have a profound impact on adaptive functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral and psychiatric manifestations in Cornelia de Lange syndrome. Grados, MA., Alvi, MH., Srivastava, S.[2020]

In a study of 50 children with Cornelia de Lange syndrome (CdLS), repetitive behaviors (RBs) and self-injurious behaviors (SIB) were found to be common, with 44% of participants exhibiting some form of SIB.

The study revealed that children with lower adaptive functioning, as measured by the Vineland Adaptive Behaviors Scales, displayed higher levels of stereotypy and SIB, indicating a significant relationship between adaptive skills and the severity of these behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive and Self-injurious Behaviors in Children with Cornelia de Lange Syndrome. Srivastava, S., Clark, B., Landy-Schmitt, C., et al.[2021]

Functional analysis is a crucial method in applied behavior analysis that helps identify the reasons behind specific target behaviors, particularly in individuals with developmental disabilities and mental illness.

Case studies highlight the practical application of functional analysis, demonstrating its effectiveness in understanding and addressing challenging behaviors by investigating their maintaining consequences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The search for functionality: the role of the environment in the development and maintenance of psychopathological symptoms. Brierley-Bowers, P.[2011]

The study explored ABA renewal, a model of treatment relapse for severe problem behavior, using undergraduate students to compare traditional ABA procedures with a modified ACA approach that reflects real-world treatment scenarios.

Both the standard ABA renewal and the modified ACA procedures resulted in similar levels of behavior recurrence, suggesting that treatment relapse can occur in both structured and more naturalistic settings, which has important implications for managing severe problem behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A nonsequential approach to the study of operant renewal: a reverse translation. Sullivan, WE., Saini, V., Roane, HS.[2019]

A systematic review of 125 studies found that applied behavior analytic (ABA) interventions are effective in increasing skills and reducing challenging behaviors in individuals with Down syndrome, showing a medium overall effect size.

Out of the reviewed studies, 36 were identified as high-quality, primarily targeting communication skills and challenging behaviors, which will inform future research directions in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Meta-Analysis of Single-Case Research on Applied Behavior Analytic Interventions for People With Down Syndrome. Neil, N., Amicarelli, A., Anderson, BM., et al.[2021]

A new methodology was developed to assess the impact of adverse side effects (ASE) from psychotropic medications on challenging behavior in individuals with intellectual and developmental disabilities (IDD), involving seven participants.

The study found that most participants showed differences in their response rates under conditions designed to evaluate ASEs, indicating that these side effects can significantly influence behavior and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Side Effects of Psychotropic Medication and Challenging Behavior: Pilot Work Assessing Impact. Valdovinos, MG., Schieber, E., McMahon, M., et al.[2020]

A study involving nine children with fragile X syndrome (FXS) found that function-based behavioral interventions led to a remarkable average reduction of 95.2% in severe problem behaviors.

The research indicates that problem behaviors in children with FXS are often driven by the need to escape demands or gain access to tangible items, similar to trends seen in the broader population with intellectual and developmental disabilities (IDD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional analysis and treatment of problem behavior exhibited by children with fragile X syndrome. Kurtz, PF., Chin, MD., Robinson, AN., et al.[2015]

Trial-based functional analyses successfully identified the functions of problem behaviors in three children within an early childhood special education setting.

Following the identification of these functions, functional communication training effectively reduced problem behaviors and increased communication skills in the children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial-based functional analysis and functional communication training in an early childhood setting. Lambert, JM., Bloom, SE., Irvin, J.[2021]

Applied Behavior Analysis (ABA) has been extensively studied for over 40 years, particularly in its effectiveness for individuals diagnosed with autism spectrum disorder (ASD), demonstrating its significance in both research and clinical settings.

The paper discusses key contributions to ABA and offers recommendations for future advancements in behavioral interventions, highlighting the ongoing evolution of practices in the next 40 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Our Understanding of Behavioral Intervention: 1980 to 2020 for Individuals Diagnosed with Autism Spectrum Disorder. Leaf, JB., Cihon, JH., Ferguson, JL., et al.[2021]

Functional Analytic Psychotherapy (FAP) utilizes behavior-analytic principles to improve interpersonal skills in adult outpatients, focusing on how therapists can provide social reinforcement to encourage positive behavioral changes.

Emerging empirical support for FAP highlights the need for further research on training therapists, conducting functional analyses, and ensuring effective treatment without creating aversive environments, presenting both challenges and opportunities for clinical behavior analysts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The challenge of understanding process in clinical behavior analysis: the case of functional analytic psychotherapy. Follette, WC., Bonow, JT.[2021]

In a case study of a 7-year-old girl with severe mental retardation and Cornelia-de-Lange syndrome, breath-holding was identified as a behavior primarily used to gain attention.

An intervention combining extinction, scheduled attention, and a picture card communication system effectively reduced the frequency of breath-holding episodes, demonstrating a successful behavioral modification strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional analysis and intervention for breath holding. Kern, L., Mauk, JE., Marder, TJ., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Behavioural phenotype of Cornelia de Lange syndrome. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Age-related Behavioural Change in Cornelia de Lange and Cri du Chat Syndromes: A Seven Year Follow-up Study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

The behavioural phenotype of Cornelia de Lange Syndrome: a study of 56 individuals. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Behavioral and psychiatric manifestations in Cornelia de Lange syndrome. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Repetitive and Self-injurious Behaviors in Children with Cornelia de Lange Syndrome. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

The search for functionality: the role of the environment in the development and maintenance of psychopathological symptoms. [2011]

7. United States pubmed.ncbi.nlm.nih.gov

A nonsequential approach to the study of operant renewal: a reverse translation. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

A Meta-Analysis of Single-Case Research on Applied Behavior Analytic Interventions for People With Down Syndrome. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Adverse Side Effects of Psychotropic Medication and Challenging Behavior: Pilot Work Assessing Impact. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Functional analysis and treatment of problem behavior exhibited by children with fragile X syndrome. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

Trial-based functional analysis and functional communication training in an early childhood setting. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Advances in Our Understanding of Behavioral Intervention: 1980 to 2020 for Individuals Diagnosed with Autism Spectrum Disorder. [2021]

13. Switzerland pubmed.ncbi.nlm.nih.gov

The challenge of understanding process in clinical behavior analysis: the case of functional analytic psychotherapy. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Functional analysis and intervention for breath holding. [2018]