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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on helping children with Cornelia de Lange syndrome (CdLS) who exhibit problem behaviors, such as aggression or self-injury. Researchers aim to identify the triggers of these behaviors and develop a treatment model to reduce them. The trial uses a special behavioral therapy called ABA-based functional analysis and treatment (Applied Behavior Analysis) to assess and address these issues. Children aged 3 to 15 with CdLS and frequent problem behaviors may qualify if their parents can attend clinic visits and implement a behavior plan at home. Families of children with CdLS who do not exhibit problem behaviors can also participate by providing regular updates for two years. As an unphased trial, this study offers families the chance to contribute to groundbreaking research that could improve the lives of children with CdLS.

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 prior data suggests that this behavioral therapy is safe for children with Cornelia de Lange Syndrome?

Research has shown that Applied Behavior Analysis (ABA) treatments are generally safe and well-tolerated. Studies have found that ABA effectively reduces problem behaviors in children. A review of research found that trial-based functional analyses, a component of ABA, can safely help manage challenging behaviors. Additionally, a retrospective study showed that when parents led ABA interventions, children experienced positive results without major safety issues. Overall, ABA treatments have a strong safety record, particularly in reducing problem behaviors in children. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how ABA-based functional analysis and treatment can help manage problem behaviors in children with Cornelia de Lange Syndrome (CdLS). Unlike typical interventions that might rely on medication or generalized behavioral strategies, this approach is personalized, focusing on understanding the specific triggers and functions of each child's behavior. This tailored technique could lead to more effective and sustainable behavioral improvements, offering new hope for families dealing with the challenges of CdLS.

What evidence suggests that this behavioral therapy is effective for problem behavior in Cornelia de Lange Syndrome?

Research has shown that ABA-based functional analysis, a treatment available in this trial, can reduce problem behaviors in children with Cornelia de Lange Syndrome (CdLS). Early results suggest these treatments can lower problem behaviors by 80% or more from the starting point. Studies have found that children with similar issues, such as those with Autism Spectrum Disorder (ASD), also benefit significantly from this method. The treatment identifies the reasons behind problem behaviors and develops specific strategies to address them. This approach successfully improves behavior by promoting positive actions and reducing negative ones. ^{1 2 6 7 8}

Who Is on the Research Team?

Patricia F Kurtz, PhD

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05829668

Behavioral Assessment and Treatment of Problem ... 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 ...

2. ctv.veeva.com ctv.veeva.com/study/behavioral-assessment-and-treatment-of-problem-behavior-in-children-with-cornelia-de-lange-syndrome

Behavioral Assessment and Treatment of Problem Behavior in ... 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 ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK1104/

Cornelia de Lange Syndrome - GeneReviews - NCBI - NIH Cornelia de Lange syndrome (CdLS) encompasses a spectrum of findings from mild to severe. Severe (classic) CdLS is characterized by distinctive facial features.

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05829668?keyword=%22Behavioral%22

San Mateo Clinical Trial Behavioral Assessment and Treatment ... Preliminary findings from functional analyses and other assessments in CdLS indicate differences in forms of problem behavior, functions for problem behavior, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10843530/

A comparative effectiveness trial of functional behavioral ... This comparative effectiveness study, conducted with 57 young children with autism spectrum disorder, evaluated the results of FBAs that did (n = 26) and did ...

6. cdlsworld.org cdlsworld.org/xwiki/bin/view/cdlsPublications/sib/SIBInterventions/

INTERVENTIONS FOR SELF-INJURIOUS BEHAVIOUR A young girl (LH) with Cornelia de Lange syndrome was described who, at age 14, had been displaying severe self-injury for ten years. Medication ...

7. researchgate.net researchgate.net/publication/259635253_A_Systematic_Review_of_Trial-Based_Functional_Analysis_of_Challenging_Behavior

A Systematic Review of Trial-Based Functional Analysis ... The purpose of this paper is to systematically review peer-reviewed studies which implemented trial-based functional analyses of challenging ...

8. pediatrics.jmir.org pediatrics.jmir.org/2024/1/e62878/

Parent-Led Applied Behavior Analysis to Impact Clinical ... Objective: This study reports findings from a retrospective chart review of clinical outcomes for children that received parent-led ABA ...