Research in Autism & OCD Fellowship

Grant Funding

Cannabidivarin (CBDV) vs. Placebo in Children with Autism Spectrum Disorder (ASD)
Funded by the DOD CDMRP Autism Research Program. The expected study duration is April 12, 2019 to June 30, 2021.

ABSTRACT: There is a clear unmet need for new therapeutics to treat irritability in children with ASD that do not have the metabolic and weight adverse event profiles of the currently approved treatments. Cannabidivarin (CBDV) is a nonpsychoactive phytocannabinoid and a safe variant of Cannabidiol (CBD). It has no appreciable tetrahydrocannabinol (THC) [less than 0.01%], has been shown to have no impact on weight or metabolism, and improves both social and cognitive functioning in animal models of idiopathic and syndromal autism (Fragile X, Rett Syndrome, Angelman Syndrome). The CDC currently estimates 1 in 59 children have ASD. ASD is characterized by deficits in social communication, irritability, repetitive behaviors, impulsivity, temper tantrums, and high caregiver burden. Currently, the only FDA-approved medications for symptoms of ASD are aripiprazole and risperidone, both of which are indicated for irritability in pediatric ASD. These medications are effective but are associated with considerable side effects with long term treatment in this chronic developmental disorder, including weight gain, metabolic syndrome and the risk of type 2 diabetes, prolactin elevation and growth of breast tissue, extrapyramidal symptoms and the risk of tardive dyskinesia. The anticonvulsant divalproex sodium (valproate/VPA) also significantly reduces irritability and repetitive behaviors in individuals with ASD. Although VPA is efficacious for pediatric epilepsy and some symptoms of ASD, it also has significant side effects, including weight gain, sedation and nausea. CBDV, like VPA, is effective in the treatment of pediatric epilepsy, and ASD mouse models demonstrate potential mechanisms for treatment with CBDV, including potential therapeutic effects on repetitive behaviors, irritability, sociability, and quality of life, and the capacity to reduce inflammation. This study aims to examine the efficacy and safety of cannabidivarin (CBDV) with a primary aim of studying its effect on irritability in children with ASD.

STUDY DESIGN: This is a 12-week randomized, double-blind study of CBDV vs. placebo in 100 child and adolescent subjects aged 5 to 18 years with a diagnosis of ASD.
Clinical Trials Link:

Intranasal Oxytocin vs. Placebo in Children with Prader-Willi Syndrome (PWS)
Funded by the FDA. The expected study duration is April 11, 2018 to February 11, 2020.

RATIONALE: Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder caused by lack of expression of paternally derived imprinted material on chromosome 15q11-q13. PWS is characterized by mild to moderate intellectual disabilities, repetitive/compulsive behaviors and rigidity, social cognition deficits and severe hypotonia at birth, followed by the onset of hyperphagia later in life. Obesity is responsible for the majority of the morbidity and mortality associated with PWS, and compulsive eating behaviors are most responsible for diminishing the quality of life for caregivers and family members. Oxytocin has been implicated in the pathophysiology of PWS and there have been small studies of intranasal oxytocin (IN-OXT) in this population. To date, however, studies have not been adequately powered to detect significance in target symptoms of hyperphagia and associated symptoms of individuals with PWS. The primary goal of this study is to examine the safety and efficacy of IN-OXT on hyperphagia, as measured by the Hyperphagia Questionnaire-Clinical Trails, from baseline to week 8. Currently, there are no effective treatments available to manage hyperphagia in patients with PWS.

STUDY DESIGN: This is an 8-week double-blind, randomized study in 50 children with PWS aged 5-17. Participation involves 5 in-person visits to our program and two telephone-call visits. Travel expenses will be reimbursed to participating families.
Clinical Trails Link:

Long-term Antipsychotic Pediatric Safety Trial (LAPS)
Funded by the Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The expected study duration is January 10, 2019 to September 10, 2021.

RATIONALE: There have been several studies in children evaluating the relationship between atypical antipsychotics and weight gain. However, these studies are limited to a relatively small number of participants (30-300) for relatively short periods of time (3-18 months). The studies that directly compare different antipsychotics to one another have very small samples of individuals on some agents, limiting their ability to detect differences in smaller groups. The purpose of this study is to evaluate the long-term pathologic weight changes associated with multi-year risperidone or aripiprazole therapy in 3 - <18-year-old children, who have varying durations of prior antipsychotic drug exposure. This is critical because children appear to have greater vulnerability to antipsychotic-associated weight gain than adults, and obesity has significant effects on morbidity and mortality.

STUDY DESIGN: This is a muli-center, observational study that will include approximately 350 children being treated with risperidone and 350 children being treated with aripiprazole. The participants’ personal physicians will continue to prescribe their medications over the course of the study. Assessments will occur every six months at in-person visits, for 2 years.
Clinical Trials Link:

aV1ation: A Study to Investigate the Efficacy and Safety of Balovaptan in Participants with Autism Spectrum Disorder (ASD)

Sponsored by Hoffmann-La Roche. The expected study duration is November 21, 2016 - July 6, 2021.

RATIONALE: To date, few studies have investigated the effect of pharmacological treatments on the social and communication deficits in ASD and no agent has received marketing approval for treating these core symptoms. Currently in the US, the only two approved medications for ASD are the atypical antipsychotics risperidone and aripiprazole, which only target irritability associated with ASD, but not the core symptoms. There is no pharmacological treatment available for the social and communication deficits in individuals with ASD and as a consequence there is a high unmet medical need for effective pharmacological therapies in the treatment of core symptoms in ASD. Balovaptan is a drug that drug blocks a hormone receptor (vasopressin 1a) in the brain that is linked to socialization, stress, anxiety, and aggression. Balovaptan has the potential to be the first pharmacotherapy to help improve core socialization and communication symptoms of ASD, and it has been granted Breakthrough Therapy Designation by the FDA.

STUDY DESIGN: This is a multi-center, randomized, double-blind, 24-week study to investigate the efficacy, safety, and pharmacokinetics of Balovaptan in children and adolescents aged 5-17 years with ASD who are high functioning (IQ >=70). After the participant completes the 24-week double-blind phase of the study, he/she will have the option to receive balovaptan in open treatment for 52 weeks.
Clinical Trails link:

oRBiting: A Study to Evaluate Scales for Repetitive and Restricted Behaviors in Children, Adolescents, and Adults With Autism Spectrum Disorder (ASD)

Sponsored by Hoffmann-La Roche. The expected study duration is August 13, 2018 to November 30, 2019.

RATIONALE: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and social interaction and presence of repetitive patterns of behaviors, interests, or activities. In addition to these core deficits, individuals with ASD may suffer from a range of co-morbid conditions and associated behavioral problems, including irritability, depression or anxiety, attention deficits, obsessive compulsive symptoms, seizures and sleep disruption. Restricted and repetitive behaviors (RRBs) are core diagnostic features of ASD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). At present, no pharmacological treatment has been approved by FDA to treat the core deficits of ASD, and currently available approved drugs (risperidone and aripiprazole) address only associated behavioral problems (used for the treatment of irritability associated with ASD). Nonpharmacological treatments have been developed to address the core symptoms; however, clear efficacy has been difficult to demonstrate in large controlled clinical trials and they are time consuming and costly. Accordingly, there is a high unmet medical need for pharmacological treatments of these core symptoms of the disorder. RRBs constitute a broad range of behaviors, including simple motor stereotypies as well as more complex ritualized and rigid behaviors, compulsions, and restricted interests that vary in frequency, intensity, and duration. Although there is an extensive literature on RRBs in subjects with ASD, the instruments available and widely used to assess these behaviors in clinical trials are not fully understood or have limitations to assess change in these behaviors, in particular in clinical trials. This study is observational and seeks to characterize different scales to measure repetitive and restricted behaviors in different ASD sub-populations over time. The study will also to explore the use of digital biomarkers. The results from this study will inform the planning and setup of subsequent drug interventional studies in programs aimed to treating restrictive and repetitive behaviors in ASD.

STUDY DESIGN: This is a 12-week study that includes 4 in-person visits to our program. The participant will also receive a smart watch and a smart phone. The smart watch will be used to monitor repetitive movements that the participant may exhibit. The smart phone will be used at home to play games that assess cognition, social skills and speech.

Clinical Trails link:

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