Pivotal Response Treatment for Autism

(PRT-I Trial)

Overseen By Estefania Millan, MA

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Severe psychiatric disorder, Genetic abnormality, Active medical problem, 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: 16

Duration: 16 weeks

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that any psychotropic medications or biomedical interventions you are taking must be stable for at least 1 month before starting the study, and you should not expect to change them during the study.

How is Pivotal Response Treatment (PRT) different from other autism treatments?

Pivotal Response Treatment (PRT) is unique because it focuses on improving pivotal areas of a child's development, such as motivation and response to multiple cues, which can lead to widespread improvements in communication, behavior, and social skills. Unlike some other therapies that may focus on specific skills, PRT aims to enhance overall learning and development by targeting these key areas. ^{1 2 3 4 5}

What is the purpose of this trial?

Autism spectrum disorder (ASD) is a very heterogeneous disorder with limited empirically validated behavioral and biological interventions. The goal of this pilot investigation is to apply a biologically-based approach to identify predictors of treatment response in children with ASD who are receiving Pivotal Response Treatment (PRT), an evidence-based behavioral intervention. Specifically, the investigators propose to identify neuroimaging biomarkers of treatment response to a PRT program (PRT-P) targeting language deficits in young children with ASD who will be randomized to either PRT-P or to a delayed treatment group (DTG).

Research Team

Antonio Hardan, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for children aged 2 to just under 5 with Autism Spectrum Disorder (ASD), who speak English, have a language delay, and can complete testing. They should not be getting more than an hour of speech therapy per week or over 15 hours of in-home ABA. Kids with severe psychiatric disorders, genetic abnormalities like Fragile X, active medical issues like unstable seizures, or previous PRT trials cannot join.

Inclusion Criteria

I have been diagnosed with Autism Spectrum Disorder.

I am between 2 and 4 years old.

My child can follow the testing procedures well enough for accurate results.

Exclusion Criteria

Previous adequate Pivotal Response Treatment (PRT) trial

Magnetic Resonance (MR) contraindication (e.g., the presence of ferrous metal)

I have a genetic condition like Fragile X.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pivotal Response Treatment Program (PRT-P) consisting of 3 parent-only sessions and 13 family sessions over 16 weeks

16 weeks

16 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pivotal Response Treatment Program (PRT-P)

Trial Overview The study tests if brain scans before treatment can predict how well young children with ASD respond to Pivotal Response Treatment (PRT-P), which focuses on improving language skills. Participants are randomly assigned to start PRT-P immediately or after a delay.

Participant Groups

Group I: Pivotal Response Treatment Program (PRT-P) Experimental Treatment 1 Intervention

The Pivotal Response Treatment Program (PRT-P) will consist of 3 parent-only sessions (60-90 min) and 13 family sessions with the parent and child (60-90 min). These 16 sessions are once per week over a 16 week period.

Group II: Delayed Treatment Group (DTG) Active Control 1 Intervention

Child continues stable treatments as usual in the community.

Pivotal Response Treatment Program (PRT-P) is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Pivotal Response Treatment for:

• Autism Spectrum Disorder (ASD)
• Language deficits in young children with ASD

Approved in Canada as Pivotal Response Treatment for:

• Autism Spectrum Disorder (ASD)
• Language deficits in young children with ASD

Approved in European Union as Pivotal Response Treatment for:

• Autism Spectrum Disorder (ASD)
• Language deficits in young children with ASD

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

Findings from Research

Pediatric brain tumor survivors treated with craniospinal irradiation (CSI) using proton radiotherapy (PRT) showed significantly worse cognitive and adaptive outcomes compared to those treated with focal PRT, indicating that the extent of radiation exposure impacts cognitive health.

Cognitive performance was found to fully mediate the relationship between the type of radiation field and adaptive functioning, suggesting that efforts to minimize radiation exposure to non-target brain tissue are crucial for improving long-term outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive mediators of adaptive functioning outcomes in survivors of pediatric brain tumors treated with proton radiotherapy. Roth, AK., Ris, MD., Orobio, J., et al.[2021]

Proton beam therapy (PBT) is feasible for treating infants with central nervous system tumors, showing promising short-term outcomes with a 3-year overall survival rate of 76.5% among 51 infants studied.

However, the treatment is associated with significant logistical challenges and potential for higher-grade toxicities, including late effects like endocrinopathy and hearing loss, highlighting the need for careful monitoring and longer follow-up to assess long-term impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study. Jazmati, D., Steinmeier, T., Ahamd Khalil, D., et al.[2021]

Proton beam radiation therapy (PRT) shows promise in maintaining stable neuropsychological functioning in pediatric brain tumor patients compared to traditional photon radiation therapy (XRT), which is associated with declining neuropsychological outcomes over time.

Despite some variability in specific cognitive areas like working memory and processing speed, the evidence suggests that PRT may reduce the risk of neuropsychological issues, although further research is needed to account for medical and sociodemographic differences among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of pediatric neuropsychological outcomes with proton versus photon radiation therapy: A call for equity in access to treatment. Peterson, RK., King, TZ.[2023]

A study of 48 children with malignant brain tumors treated with proton beam therapy (PBT) showed that acute toxicities were generally low-grade and manageable, with fatigue, alopecia, and dermatitis being the most common side effects.

The research indicates that PBT is well tolerated in pediatric patients, and acute toxicities can be effectively managed with supportive care, suggesting a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity of proton beam radiation for pediatric central nervous system malignancies. Suneja, G., Poorvu, PD., Hill-Kayser, C., et al.[2013]

In a study of 595 pediatric patients treated with proton radiation therapy (PBT) for brain tumors, only 3.2% developed symptomatic brainstem injury (SBI), indicating a relatively low risk of this serious complication.

The implementation of strict brainstem dose constraints in 2014 led to a trend of reduced SBI incidence from 4.4% to 1.5%, suggesting that careful dose management can enhance safety without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantifying the risk and dosimetric variables of symptomatic brainstem injury after proton beam radiation in pediatric brain tumors. Upadhyay, R., Liao, K., Grosshans, DR., et al.[2023]

References

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

Cognitive mediators of adaptive functioning outcomes in survivors of pediatric brain tumors treated with proton radiotherapy. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study. [2021]

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

A systematic review of pediatric neuropsychological outcomes with proton versus photon radiation therapy: A call for equity in access to treatment. [2023]

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

Acute toxicity of proton beam radiation for pediatric central nervous system malignancies. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Quantifying the risk and dosimetric variables of symptomatic brainstem injury after proton beam radiation in pediatric brain tumors. [2023]