Group CBT in Adolescents With Fragile X Syndrome and in Adolescents With Autism Spectrum Disorder

NCT ID: NCT06677866

Last Updated: 2024-11-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2025-12-31

Brief Summary

Fragile X Syndrome (FXS) is a rare genetic syndrome, caused by a mutation in the FMR1 gene located on the X chromosome. It is considered the leading hereditary cause of intellectual disability (ID) and the primary cause of Autism Spectrum Disorder (ASD) due to a single gene-mutation. Many individuals with FXS exhibit symptoms overlapping with those of ASD, including difficulties in social-communication skills, challenges in peer relationships, restricted and repetitive behaviors/interests and deficits in adaptive functioning. Both in ASD and FXS, individuals with greater deficits in executive functions, socio-pragmatic, and socio-relational skills also demonstrate lower adaptive functioning and, consequently, reduced autonomy/independence throughout the life course and greater severity of the disorder.

Among empirically validated treatments recommended by National and International Guidelines for the treatment of ASD, cognitive-behavioral and psychosocial interventions have been shown to improve some aspects of ASD, such as core symptoms, emotional-behavioral disturbances, adaptive skills, and quality of life. Currently, it appears that cognitive-behavioral therapies, which include psychoeducation programs, are particularly appropriate for ASD, with greater efficacy for group interventions compared to individual ones. Regarding FXS, despite the well-established knowledge of the cognitive-behavioral phenotype and the clear need for scientifically validated programs, research on intervention strategies remains quite limited.

Considering the similarities between ASD and FXS and the need for standardized interventions, the present research project aims to conduct an RCT to evaluate the feasibility of Cooperative Group Therapy (CGT) in two different groups of adolescents with ASD and FXS. The decision to target the intervention to adolescents is due to the few clinical studies on this age group, which is a crucial target since, in FXS, there is often a plateau or reversal of intellectual and adaptive development after the age of 10, and in adolescents with ASD, the development and complexity of social, pragmatic skills, and executive functions are crucial for good adaptive functioning and a basic quality of life. Te main hypothesis is that CGT could contribute to the reduction of severity illness and in the enhancement of socio-communicative skills.

Detailed Description

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder affecting approximately 1% of the global population, characterized by early onset, difficulties in communication and reciprocal social interaction, and associated with unusually restricted and repetitive behaviors and interests.

Fragile X Syndrome (FXS) is a rare genetic syndrome affecting about 1 in 4.,000 males and 1 in 8.,000 females, caused by a mutation in the FMR1 gene located on the X chromosome. It is considered the leading hereditary cause of intellectual disability (ID) and the primary cause of ASD due to a mutation in a single gene.

Research shows that many individuals with FXS exhibit symptoms overlapping with those of ASD, including difficulties in social-communication skills, challenges in peer relationships, restricted and repetitive behaviors/interests, and deficits in adaptive functioning. In both syndromes, individuals with greater deficits in executive functions, socio-pragmatic, and socio-relational skills also demonstrate lower adaptive functioning and, consequently, reduced autonomy/independence throughout the life course and greater severity of the disorder.

Among empirically validated treatments recommended by National and International Guidelines for the Treatment of Autism, cognitive-behavioral and psychosocial interventions have been shown to improve some aspects of ASD, such as core symptoms, emotional-behavioral disturbances, adaptive skills, and quality of life. Currently, it appears that cognitive-behavioral therapies, which include psychoeducation programs, are particularly appropriate for ASD, with greater efficacy for group interventions compared to individual ones. However, a very recent meta-analysis of Conrad and colleagues (2021) highlighted that there are currently only 30 RCTs (Randomized Clinical Trials) on ASD and that most of these studies have been conducted in a limited geographical area, with few studies in Europe. Regarding FXS, despite the well-established knowledge of the cognitive-behavioral phenotype and the clear need for scientifically validated programs, research on intervention strategies remains quite limited. In a 2011 systematic review, Moskowitz and Carr analyzed 31 studies investigating the effectiveness of behavioral treatment in FXS and pointed out that most of them were conducted with limited methodological rigor. Indeed, their review revealed that the examined interventions employed various behavioral strategies, often using a single patient per technique, making it difficult to draw conclusions about individual techniques. The lack of empirically validated cognitive-behavioral intervention models remains a significant issue for all clinicians working with individuals with FXS and ASD. Consequently, parents continue to rely on intervention methods whose clinical effectiveness has not been tested, monitored, or replicated through studies with valid methodological rigor. As a result, there is an undeniable need to develop new interventions: a) conducted with methodological rigor (RCTs), b) applicable across different age groups, and c) structured, empirically measurable, and replicable.

In 2020, Valeri and colleagues conducted the first European RCT to assess the clinical effectiveness of Cooperative Parent-Mediated Therapy (CPMT) in preschool children with Autism, showing that CPMT is effective in improving socio-communication skills, core ASD symptoms, and in reducing parental stress related to dysfunctional parent-child interactions.

Subsequently, in 2021, Alfieri and colleagues conducted a study to verify the efficacy of CPMT in treating socio-communicative deficits in children with FXS and Williams Syndrome, demonstrating that the use of a parent-mediated intervention, theoretically founded and utilizing ECEN strategies (Evolutive and Naturalistic Behavioral Interventions), results in significant improvement in socio-communicative-relational skills even in these populations.

Additionally, Montanaro and coll. in 2020 performed a study to examine the efficacy of Corp-osa-Mente (CoM), a combined neuropsychological and cognitive behavioral group therapy (nCBT) tailored on young adults and targeting the different clinical manifestations of FXS through a unified approach. Results indicated an improvement in participants' psychopathological symptoms, cognitive abilities, and general adaptive behavior. However the study faced different methodological issues, such as the absence of standardized measures. Therefore, additional methodologically rigorous studies were required to substantiate these initially promising findings.

Based on these encouraging results in children and adults with FXS, the present research project aims to conduct an RCT to evaluate the clinical efficacy and feasibility of Cooperative Group Therapy (CGT) in two different groups of adolescents with ASD and FXS. The decision to target the intervention to adolescents is due to the few clinical studies on this age group, which is a crucial target since, in FXS, there is often a plateau or reversal of intellectual and adaptive development after the age of 10, and in adolescents with ASD, the development and complexity of social, pragmatic skills, and executive functions are crucial for good adaptive functioning and a decent quality of life. Specifically, the primary goal is the reduction of the mean score on the Global Clinical Impression - Severity Scale (CGI-S), which measures the severity of the disorder, after treatment compared to baseline. Pre- and post-treatment evaluations of cognitive and adaptive profiles will also be conducted, and standardized questionnaires will be administered, with results used as secondary endpoints (e.g., Social Responsiveness Scale, SRS; Behavior Rating Inventory of Executive Functioning, BRIEF; Vineland Adaptive Behavior Scales -II, VABS-II; Multidimensional Anxiety Scale for Children-II, MASC II; Child Behavior Checklist, CBCL; Conners' Parent Rating Scale, CPRS; Quality of Life Scale, QoLS; Parenting Stress Index, PSI).

Conditions

Fragile X Syndrome (FXS); Autism Spectrum Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ASD-CGT- Treatment group (ASD-CGT)

Group of adolescents with ASD that perform the intervention at the beginning of the study (ASD-CGT)

Group Type: EXPERIMENTAL

Cognitive behavioral therapy

Intervention Type: BEHAVIORAL

Cooperative Group Therapy (CGT) is a cognitive-behavioral group therapy based on the theoretical and practical principles of the Cooperative Parent-Mediated Therapy model [Valeri et al., 2020].

The goal of CGT is to promote the following core skills: Pragmatics, Executive Functions, and Cooperative Interactions. The CGT program consists of 15 sessions over a total duration of 6 months: 12 group therapy sessions with adolescents and 3 sessions with their parents. Each session focuses on a specific topic and lasts between 90 and 120 minutes.

The CGT therapist is a psychotherapist with a cognitive-behavioral orientation who utilizes evidence.-based strategies to enhance pragmatic, socio-conversational skills, cognitive flexibility, emotional regulation, and cooperative interactions. The CGT intervention is conducted by two cognitive-behavioral psychotherapists specialized respectively in the treatment of FXS and ASD.

FXS- Waiting List group (FXS-WL)

Group of adolescents with FXS that perform the intervention once that the sections with the first group are ended (FXS-WL)

Group Type: OTHER

Waiting List

Intervention Type: OTHER

The Waiting List (WL) is a control group in which participants who do not receive the experimental treatment are placed on a waiting list to receive the intervention after the active treatment group has completed it. In the case of the WL, the CGT intervention is carried out after at least 6 months to allow the patients in the first group to complete the treatment cycle. This approach enables a comparison between a group of treated patients and a group of patients who have not yet been treated, while still allowing the latter to access the treatment at a later stage.

FXS- CGT- Treatment group (FXS-CGT)

Group of adolescents with FXS that perform the intervention at the beginning of the study (FXS-CGT)

Group Type: EXPERIMENTAL

Cognitive behavioral therapy

Intervention Type: BEHAVIORAL

Cooperative Group Therapy (CGT) is a cognitive-behavioral group therapy based on the theoretical and practical principles of the Cooperative Parent-Mediated Therapy model [Valeri et al., 2020].

The goal of CGT is to promote the following core skills: Pragmatics, Executive Functions, and Cooperative Interactions. The CGT program consists of 15 sessions over a total duration of 6 months: 12 group therapy sessions with adolescents and 3 sessions with their parents. Each session focuses on a specific topic and lasts between 90 and 120 minutes.

The CGT therapist is a psychotherapist with a cognitive-behavioral orientation who utilizes evidence.-based strategies to enhance pragmatic, socio-conversational skills, cognitive flexibility, emotional regulation, and cooperative interactions. The CGT intervention is conducted by two cognitive-behavioral psychotherapists specialized respectively in the treatment of FXS and ASD.

ASD- Waiting List group (ASD-WL)

Group of adolescents with ASD that perform the intervention once that the sections with the first group are ended (ASD-WL)

Group Type: OTHER

Waiting List

Intervention Type: OTHER

The Waiting List (WL) is a control group in which participants who do not receive the experimental treatment are placed on a waiting list to receive the intervention after the active treatment group has completed it. In the case of the WL, the CGT intervention is carried out after at least 6 months to allow the patients in the first group to complete the treatment cycle. This approach enables a comparison between a group of treated patients and a group of patients who have not yet been treated, while still allowing the latter to access the treatment at a later stage.

Interventions

Cognitive behavioral therapy

Cooperative Group Therapy (CGT) is a cognitive-behavioral group therapy based on the theoretical and practical principles of the Cooperative Parent-Mediated Therapy model [Valeri et al., 2020].

The goal of CGT is to promote the following core skills: Pragmatics, Executive Functions, and Cooperative Interactions. The CGT program consists of 15 sessions over a total duration of 6 months: 12 group therapy sessions with adolescents and 3 sessions with their parents. Each session focuses on a specific topic and lasts between 90 and 120 minutes.

The CGT therapist is a psychotherapist with a cognitive-behavioral orientation who utilizes evidence.-based strategies to enhance pragmatic, socio-conversational skills, cognitive flexibility, emotional regulation, and cooperative interactions. The CGT intervention is conducted by two cognitive-behavioral psychotherapists specialized respectively in the treatment of FXS and ASD.

Intervention Type: BEHAVIORAL

Waiting List

The Waiting List (WL) is a control group in which participants who do not receive the experimental treatment are placed on a waiting list to receive the intervention after the active treatment group has completed it. In the case of the WL, the CGT intervention is carried out after at least 6 months to allow the patients in the first group to complete the treatment cycle. This approach enables a comparison between a group of treated patients and a group of patients who have not yet been treated, while still allowing the latter to access the treatment at a later stage.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of FXS confirmed by genetic testing.
• Age between 13 and 19 years.
• Language skills compatible with group intervention (verbal language at sentence level).
• Impairment in adaptive functioning measured by VABS II < 70.

• Clinical diagnosis of Autism Spectrum Disorder (ASD) confirmed by ADOS-2 and ADI-R interviews.
• Age between 13 and 19 years.
• Language skills compatible with group intervention (verbal language at sentence level).
• Impairment in adaptive functioning measured by VABS II < 70.
• Informed consent for participation and data processing provided by parents.

Exclusion Criteria

• Severe visual or hearing impairments.
• Diagnosis of epilepsy or a history of seizures requiring medication.
• Participation in other non-pharmacological treatments.
• Changes in pharmacological therapy within the last 3 months.
• Presence of medical problems or behaviors that could interfere with group activities, as measured by the Autism Behavior Checklist (ABC) (ABC Irritability Scale < 18).
• IQ < 40 measured by the Leiter third edition (Leiter 3)
• Severe adaptive functioning, measured by VABS II < 20.

ASD group:

• Severe visual or hearing impairments.
• Identification of specific genetic abnormalities or presence of known genetic syndromes associated with ASD (e.g., TSC, FXS, 22q11, 16p11.2, Rett Syndrome).
• Diagnosis of epilepsy or a history of seizures requiring medication.
• Participation in other non-pharmacological treatments.
• Changes in pharmacological therapy within the last 3 months.
• Presence of medical problems or behaviors that could interfere with group activities, as measured by the Autism Behavior Checklist (ABC) (ABC Irritability Scale < 18).
• IQ < 40 measured by the Leiter third edition (Leiter 3)
• Severe adaptive functioning, measured by VABS II < 20.

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Paolo Alfieri

medical doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paolo Alfieri, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Bambino Gesù Children's Hospital

Stefano Vicari, MD, clinical professor

Role: STUDY_CHAIR

Bambino Gesù Hospital and Research Institute

Locations

Bambino Gesù Children's Hospital

Rome, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Alice Federica M Montanaro, PsyD

Role: CONTACT

federica.montanaro@opbg.net

06/68597009 ext. +39

Paolo Alfieri, MD, PhD

Role: CONTACT

paolo.alfieri@opbg.net

06/685974721 ext. +39

Facility Contacts

Elisa Zaccagnini

Role: primary

elisa.zaccagnini@opbg.net

06/68592735

References

Valeri G, Casula L, Menghini D, Amendola FA, Napoli E, Pasqualetti P, Vicari S. Cooperative parent-mediated therapy for Italian preschool children with autism spectrum disorder: a randomized controlled trial. Eur Child Adolesc Psychiatry. 2020 Jul;29(7):935-946. doi: 10.1007/s00787-019-01395-5. Epub 2019 Sep 23.

Reference Type: RESULT

PMID: 31549310 (View on PubMed)

Alfieri P, Scibelli F, Casula L, Piga S, Napoli E, Valeri G, Vicari S. Cooperative Parent-Mediated Therapy in Children with Fragile X Syndrome and Williams Beuren Syndrome: A Pilot RCT Study of a Transdiagnostic Intervention-Preliminary Data. Brain Sci. 2021 Dec 23;12(1):8. doi: 10.3390/brainsci12010008.

Reference Type: RESULT

PMID: 35053752 (View on PubMed)

Montanaro FAM, Alfieri P, Caciolo C, Spano G, Bosco A, Vicari S. Effects of a combined neuropsychological and cognitive behavioral group therapy on young adults with Fragile X Syndrome: An explorative study. Res Dev Disabil. 2024 Nov;154:104839. doi: 10.1016/j.ridd.2024.104839. Epub 2024 Sep 26.

Reference Type: RESULT

PMID: 39332280 (View on PubMed)

Other Identifiers

2850_OPBG_2022

Identifier Type: -

Identifier Source: org_study_id