Guanfacine XR for Aggression and Self Injury in PWS A Double Blind Placebo Controlled Trial

Funding Summary

Guanfacine XR (brand name Intuniv) is a medication for ADHD that improves impulse control. Dr. Singh has noted improvements in aggression and self injury in PWS patients in his practice when using this medication. In this study, he will perform a pragmatic clinical trial to evaluate the efficacy of guanfacine for treating these aspects of PWS, and also evaluate the safety and tolerability of the medication in the PWS population. 

 Theresa Strong, Director of Research Programs, shares details on this project in this short video clip. 

 

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Lay Abstract

Aggression towards self and others, oppositional behavior, and temper tantrums frequently occur in patients with Prader-Willi Syndrome (PWS). PWS also has a higher prevalence of self-injury, impulsivity, inattention, and hyperactivity. Yet, there are limited therapeutic resources to address the behavioral problems associated with this complex genetic condition. Currently, selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotics are the most frequently utilized medications to manage aggression and skin-picking behavior in PWS. However, both types of medications are associated with risks of obesity and metabolic syndrome, amongst other side effects. Since prevention of metabolic syndrome is paramount to improving the quality of life of patients with PWS, better options must be explored.

Guanfacine Extended Release (GXR) is a medicine that works by improving impulse control. It is well studied and has been determined to be safe and effective in treating children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). GXR has also been shown to reduce ADHD symptoms and aggression in children with Autism Spectrum Disorder (ASD). A published case-report on a patient with PWS seen by the Principal Investigator (PI) in this submission demonstrated a significant reduction in aggression and skin-picking behavior in an aggressive fourteen-year-old female with PWS treated with GXR. The PI has since gathered qualitative evidence on 17 patients with PWS who were treated with GXR. The analysis of data showed a significant improvement in aggressive symptoms and symptoms of ADHD. Although fewer patients were treated for skin-picking, the results suggested an improvement. Overall, GXR was well tolerated with limited side effects. These findings further support the reduction of aggression and self-injury in PWS treated with GXR.

Based on the above preliminary findings, along with the relative safety of GXR, including the absence of metabolic side effects, we propose a placebo-controlled clinical trial to assess the utility of GXR in the management of patients with PWS who have significant aggression or self-injury. We will also establish the safety of GXR with a specific focus on metabolic effects.

A placebo-controlled research method will help determine the efficacy of GXR in treating these symptoms while addressing possible confounding variables. Following the blinded phase of the trial, an open-label phase will be pursued to further evaluate the efficacy and tolerability of GXR. In addition, this will make GXR available to all participants who did not get its benefits in the blinded phase.

If a positive response is seen to GXR, the investigators would like to embark on the wide-spread education of patients, families, and clinicians about its practical use in real-world settings.

 

Funded Year:

2018

Awarded to:

Deepan Singh, MD

Amount:

$108,000

Institution:

NYU Winthrop Hospital

Researcher:

Deepan Singh, MD

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