A randomized double-blind placebo-controlled clinical trial of Guanfacine Extended Release for aggression and self-injurious behavior associated with Prader-Willi Syndrome

Introduction: Prader-Willi Syndrome (PWS), a rare genetic disorder, affects development and behavior, frequently resulting in self-injury, aggression, hyperphagia, oppositional behavior, impulsivity and over-activity causing significant morbidity. Currently, limited therapeutic options are available to manage these neuropsychiatric manifestations. The aim of this clinical trial was to assess the efficacy of guanfacine-extended release (GXR) in reducing aggression and self-injury in individuals with PWS. Trial Design: Randomized, double-blind, placebo-controlled trial conducted under IRB approval. Methods: Subjects with a diagnosis of PWS, 6-35 years of age, with moderate to severe aggressive and/or self-injurious behavior as determined by the Clinical Global Impression (CGI)-Severity scale, were included in an 8-week double-blind, placebo-controlled, fixed-flexible dose clinical trial of GXR, that was followed by an 8-week open-label extension phase. Validated behavioral instruments and physician assessments measured the efficacy of GXR treatment, its safety and tolerability. Results: GXR was effective in reducing aggression/agitation and hyperactivity/noncompliance as measured by the Aberrant Behavior Checklist (ABC) scales (p=0.03). Overall aberrant behavior scores significantly reduced in the GXR arm. Aggression as measured by the Modified Overt Aggression Scale (MOAS) also showed a significant reduction. Skin-picking lesions as measured by the Self Injury Trauma (SIT) scale decreased in response to GXR. No serious adverse events were experienced by any of the study participants. Fatigue /sedation was the only adverse event significantly associated with GXR. The GXR group demonstrated significant overall clinical improvement as measured by the CGI-Improvement (CGI-I) scale. (p<0.01). Conclusion: Findings of this pragmatic trial strongly support the use of GXR for treatment of aggression, skin picking, and hyperactivity in children, adolescents, and adults with PWS. Trial Registration: ClinicalTrials.gov Identifier - NCT05657860