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Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism

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ClinicalTrials.gov Identifier: NCT03337646
Recruitment Status : Recruiting
First Posted : November 9, 2017
Last Update Posted : September 27, 2018
Sponsor:
Collaborator:
Shire
Information provided by (Responsible Party):
JPM van Stralen Medicine Professional

Tracking Information
First Submitted Date  ICMJE November 5, 2017
First Posted Date  ICMJE November 9, 2017
Last Update Posted Date September 27, 2018
Actual Study Start Date  ICMJE September 26, 2018
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2017)
ADHD Symptoms [ Time Frame: 12 weeks ]
Physician rated scale ADHD IV-RS each item is scaled 1 to 3 with a total between 0 and 54
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03337646 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2017)
  • Health Related Quality of Life [ Time Frame: 12 weeks ]
    Parent completed rating scale called Child Health and Illness Profile- Child Edition: Parent Report Form ( CHIP-CE-PRF) . This is a generic child health status questionnaire that comprehensively describes all aspects of child health that can be influenced by the health care and school systems. It includes subdomains of satisfaction, discomfort, resilience, risk avoidance, achievement, and disorders. The domains and subdomains were conceptually derived and generally supported by factor analysis. The majority of items assess frequency of behaviors or experiences. Most items use a five-point response format. When a recall period is used, it is typically the past 4 weeks. Scale scores are obtained by computing the average of the individual item responses, whether scoring the domain or subdomain (in the PRF). The scale scores are standardized with a mean of 50 and standard deviation of 10. Higher scores indicate better health.
  • Executive Function [ Time Frame: 12 weeks ]
    The BRIEF-P is a 90 item parent completed questionnaire with a global executive composite score (GEC). GEC is reported as a t-score and a t-score of less than 65 is within normal limits
  • Severity of illness [ Time Frame: 12 weeks ]
    The severity of illness using the Clinical Global Impression-severity of illness, a 7 point scale which is physician rated
  • Improvement of Subjects [ Time Frame: 12 weeks ]
    The severity of illness using the Clinical Global Impression-improvement of illness, a 7 point scale which is physician rated To evaluate the change in functional impairment in subjects. A score of 1 indicates very much improved while a score of 7 indicates very much worse
  • Safety-Adverse events [ Time Frame: 12 weeks ]
    Adverse events are recorded at every visit
  • Safety - suicidality [ Time Frame: 12 weeks ]
    Using the Columbia-Suicide Severity Rating Scale the incidence of suicidal thoughts and actions are recorded. The C-SSRS (Posner et al. 2011; Posner et al. 2010) is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviours during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour has occurred.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
Official Title  ICMJE A Multi-Center, Open Label, Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder
Brief Summary The purpose of this study is to evaluate the effect and safety of Lisdexamfetamine dimesylate (Vyvanse®) in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents with ADHD and comorbid Autism Spectrum Disorder (ASD). This would be a novel study as there is no known safety or efficacy data for amphetamine based medications in this population. In addition, although health related quality of life and executive function are known to improve with the treatment of lisdexamfetamine dimesylate in the ADHD population (Banaschewski 2013; Findling 2009; Turgay 2010), it has not been shown in the co‐morbid ADHD and ASD population. ADHD is the most common pediatric neurobiological condition affecting approximately five percent of the pediatric population (Feldman 2009). ASD is being increasingly recognized as affecting a substantial amount of the pediatric population, with recent prevalence data showing 1 in 68 affected (Baio, 2014). Prior to the introduction of DSM‐5 (APA, 2013), exclusion criteria precluded the diagnosis of ADHD when ASD was present. Studies have shown that 41%‐71% of children with ASD also meet criteria for ADHD (Goldstein 2004, Sturm 2004,Yoshida 2004, Gadow 2006). This means that up to 1% of the population may have co‐morbid ADHD and ASD. With the official recognition of this comorbidity, treatment of comorbid ADHD when ASD is also present has been increasingly recognized as an important strategy in improving executive functioning and quality of life in those affected. Studies have indicated that some of the medications commonly used to treat ADHD, are effective and safe when used in comorbid ADHD and ASD. At this time, there have been well designed studies demonstrating safety and efficacy for methylphenidate (Ghuman et al. 2009; Handen et al. 2000; Quintana et al. 1995; RUPP 2005), guanfacine XR (Posey 2004; Scahill 2015), and atomoxetine (Arnold 2006; Harfterkamp 2012).
Detailed Description

ADHD is the most common pediatric neurobiological condition affecting approximately five percent of the pediatric population (Faraone, Stephen V., Sergeant, J. et al. 2003; Feldman & Belanger 2009). ASD is being increasingly recognized as affecting a substantial amount of the pediatric population, with recent prevalence data showing 1 in 68 affected (U.S. Department of Health and Human Services 2010). Prior to the introduction of DSM-5, exclusion criteria precluded the diagnosis for ADHD when ASD was present (American Psychiatric Association 2013). Studies have shown that 41%-71% of children with ASD also meet criteria for ADHD, meaning up to 1% of the population may have comorbid ADHD and ASD (Goldstein & Schewbach 2004).

With the official recognition of comorbidity, treatment of comorbid ADHD when ASD is also present has been increasingly recognized as an important strategy in decreasing ADHD symptoms, and improving executive functioning and quality of life of those affected. Studies have indicated that some of the medications (methylphenidate, guanfacine XR and atomoxetine) commonly used to treat ADHD are effective and safe when used in comorbid ADHD and ASD (Ornstein & Kollins 2012; Ghuman et al. 2009; Handen et al. 2000; Quintana et al. 1995; Posey et al. 2004; Scahill et al. 2015; M. et al. 2012). While amphetamine class compounds are amongst the first line of treatment in ADHD, the lack of studies in this population has discouraged their use in subjects with comorbid ADHD and ASD.

The lack of safety and efficacy data is problematic as it limits therapeutic options for the population of subjects with ADHD and ASD. Amphetamines and methylphenidate medications are equally considered first line treatment options for ADHD (CADDRA 2011). Some subjects may preferentially respond to one group of medications over another, therefore it is important to have clear safety and efficacy data for both therapeutic options.

A retrospective chart review of this population indicates that treatment is started with methylphenidate versus combined amphetamine/dextroamfetamine at a ratio of 2.78:1 (Stigler et al. 2004). Due to the availability of evidence of efficacy in this comorbid population, clinicians may choose to skip to what is considered a second line medication for ADHD symptomatology rather than using LDX (or another amphetamine-based ADHD medication such as dexedrine or Adderall XR) that may have a larger effect size for treating these symptoms.

LDX has been shown to be an effective treatment for ADHD in subjects 6 and above. With long lasting effectiveness shown to last up to 14 hours, it could potentially improve ADHD symptoms and overall quality of life for children and adolescents with ADHD and ASD in home, school and after-school functioning.

The purpose of this study is to evaluate the safety and efficacy of LDX in treating ADHD when ASD is co-morbid.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Multi-Center Open Label
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Attention Deficit Hyperactivity Disorder
  • Autism Spectrum Disorder
Intervention  ICMJE Drug: Lisdexamfetamine Dimesylate
Medication to treat ADHD
Other Name: Vyvanse
Study Arms  ICMJE Lisdexamphetamine
All participants will receive Lisdexamfetamine Dimesylate (LDX) at an optimized dose based on protocol
Intervention: Drug: Lisdexamfetamine Dimesylate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 7, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female subject aged 6-12 years at the time of consent/assent.
  2. Subjects parent(s) or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) by the subject in accordance with the International Council on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (1996), any updates or revisions, and applicable regulations, before completing any study related procedures.
  3. Subject and parent(s)/LAR are willing and able to comply with all of the requirements defined in the protocol.
  4. Subject meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria for a diagnosis of ADHD combined presentation, inattentive presentation or hyperactive/impulsive presentation based on history and a minimum ADHD-RS score of 32 and a minimum CGI-S of 4 at baseline.
  5. Subject meets DSM-V criteria for a diagnosis of ASD-level 1 based on history and Autism Diagnostic Observation Scale (ADOS-2).
  6. Subject has an SRS-2 total score of ≥ 70.
  7. Subject has a Clinical Global Impressions - Severity of Illness (CGI-S) score ≥ 4 at the baseline visit (visit 2)
  8. Subject has a blood pressure measurement within 95th percentile for age, and sex (Appendix 1,1.1,2 & 2.2). Subject and parent/legally authorized representative (LAR) are willing, able and likely to comply with the study procedures and restrictions within the protocol.

Exclusion Criteria:

  1. Subject has any condition that, in the opinion of the investigator, represent an inappropriate risk to the subject or may confound the interpretation of the study.
  2. Subject has a known history or presence of structural cardiac abnormalities, cardiovascular or cerebrovascular disease, serious heart rhythm abnormalities, syncope, tachycardia, cardiac conduction problems (such as clinically significant heart block or QT interval prolongation), exercise-related cardiac events including syncope and pre-syncope or clinically significant bradycardia.
  3. Subject has a known history of symptomatic cardiovascular disease, unexplained syncope, exertional chest pain, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease or other serious cardiac problems placing them at increased vulnerability to sympathomimetic effects of a stimulant drug.
  4. Subject has a history of seizure disorder (other than a single childhood febrile seizure occurring before the age of 3 years).
  5. Subject has glaucoma.
  6. Subject is currently using prohibited medication.
  7. Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to LDX.
  8. Subject has taken another investigational product within 30 day prior to baseline.
  9. Subject has initiated behavioural therapy within 1 month of the baseline visit (visit 0). Subject may not initiate behavioural therapy during the study.
  10. Subject is female and is pregnant or currently lactating.
  11. Subject is currently considered a suicide risk in the opinion of the investigator, has previously made a suicide attempt, or has a prior history of or is currently demonstrating active suicide ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the investigator.
  12. History of failure to respond to an adequate trial of an amphetamine based medication.
  13. Subject is currently abusing an illicit substance or lives with someone known to currently abuse stimulants or cocaine..
  14. Subject has a known renal or hepatic insufficiency.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 12 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Judy van Stralen, MD 613-726-7436 judy@cfpe.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03337646
Other Study ID Numbers  ICMJE RES 16-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party JPM van Stralen Medicine Professional
Study Sponsor  ICMJE JPM van Stralen Medicine Professional
Collaborators  ICMJE Shire
Investigators  ICMJE
Principal Investigator: Judy van Stralen, MD Center for Pediatric Excellence
PRS Account JPM van Stralen Medicine Professional
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP