A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

Principal Investigator: MINSHEW, NANCY J
Institution Receiving Award: PITTSBURGH, UNIVERSITY OF
Program: ARP
Proposal Number: AR100344
Award Number: W81XWH-11-1-0665
Funding Mechanism: Clinical Trial Award
Partnering Awards:
Award Amount: $1,412,388.00


The majority of people with autism spectrum disorder (ASD), including those considered "high functioning," enter adulthood with major limitations in life skills that substantially impede their capacity to achieve independent living, work at a job commensurate with their strengths, and enjoy a good quality of life. The need for specific interventions for adults with ASD that address these issues is profound. This need will be answered in many different ways in the 21st century, reflecting the many different underlying mechanisms and causes of ASD and the wide range of severity. The present study focuses on a new cognitive rehabilitation intervention for verbal adults with ASD that shows great promise. It is called Cognitive Enhancement Therapy or CET. "Cognitive" means thinking or thought processes, and CET is targeted toward improving the underlying cognitive impairments in ASD that limit functioning.

Because of extensive research advances in defining the cognitive and brain mechanisms underlying the manifestations of ASD, it is now possible to identify a cognitive rehabilitation intervention that more specifically targets the cognitive and neurologic obstacles limiting the function of adults with ASD. CET therapy was first developed for individuals with schizophrenia with similar impairments and symptoms to verbal adults with ASD. CET was demonstrated in two large National Institutes of Health (NIH) trials to be very effective (moderate to large effect) in improving the capacity of these individuals with schizophrenia to process information, understand the views of others, and regulate their emotions in daily life. These improvements led to substantially better capacity to work and get along with others, to hold jobs, and live independently. Because less severely affected individuals with schizophrenia and high-functioning individuals with ASD have similar cognitive and affective deficits in theory of mind, perspective-taking, abstraction, face processing, voice melody, inflexibility, and slow speed of thinking among others, we began adapting CET for use in ASD in a NIH-supported pilot study of 14 verbal adults with ASD. This pilot study has demonstrated excellent acceptance, 100% retention, no adverse effects, and improved processing speed at the early phase in these ASD adults. This pilot study will be complete by the time of funding of the proposed study. This evidence supports the need for the first controlled study of the efficacy of CET for verbal adults with ASD. We anticipate CET will improve their speed of thinking, ability to see others' points of view, flexibility of thinking and acting, and capacity to manage emotions and solve problems in everyday life. This study will also test if these effects can be maintained for 6 months after the 18 months of treatment ends (durability) and if the treatment causes changes in brain connections that support these improvements (brain basis).

CET is ultimately likely to help about 20%-30% of adult individuals diagnosed with ASD. CET may also be shown to be applicable at younger ages. CET for ASD may also generate sub-components that are more widely applicable in ASD. The goal and expectation for CET is to address the issues not addressed by other interventions -- to increase the speed at which the brain is able to process information and to use the adult mind to learn social, emotional, and problem-solving skills that did not naturally develop. These improvements will increase employability, the ability to live independently, and the capacity to live less stressful, more comfortable lives. CET therapy is provided for 18 months, and clinically relevant improvement is anticipated in that period of time. This intervention methodology can be taught to individuals with college degrees including teachers and thus has the potential to be widely available at a reasonable cost. The risks are minimal and consist largely of the stress of talking about issues that represent the areas of greatest difficulty. We are 9 months into the pilot study and none of the 14 pilot participants has experienced an adverse event, none has left the study, and attendance has been excellent. The study we are proposing will provide the beginning evidence of CET efficacy that will support an application to NIH for a large-scale trial. Evidence of this type is essential to changing public policy and insurance coverage and thus to making CET available in the community.

We expect that this study will result in more verbal adults with ASD being able to work and live independently and in community providers having more appropriate skills to support and help verbal ASD adults. We also expect CET trials to begin at a number of sites around the country once sufficient evidence of initial efficacy is provided so that independent replication of methods and results occurs. Once CET efficacy in ASD is established, we will design a CET maintenance program so that community providers can give appropriate ongoing support and help during crises.