Clinical trial NCT03730870: Pharmacogenomics for Improving Pediatric ADHD Treatment
Official title: Assessment of Pharmacogenomics Testing for Improving Pediatric ADHD Psychopharmacological Treatment: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Attention Deficit Disorders With Hyperactivity
Keywords: Attention Deficit Disorders with Hyperactivity
ADHD
Pharmacogenomics
Pediatric ADHD
ADHD medications
Lead sponsor: Clinical and Translational Genome Research Institute, Inc.
Sponsor class: OTHER
Collaborators: name: Children's Specialized Hospital
First posted: 2018-11-05
Enrollment: 21
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to have their study clinician have access to their pharmacogenomics report prior to prescribing medications (experimental group) or no access (control group) until end of the study.
Primary purpose: TREATMENT

Brief summary: This research study is a randomized controlled trial (RCT) to test whether pharmacogenomics (PGx) testing for ADHD medications will help guide clinicians to choose medications and dosages for pediatric ADHD treatment that provide faster symptom relief, fewer or less severe side effects, improve patient quality of life, and lessen emotional stress for parents/guardians of the patients.

Detailed description: The study is a randomized controlled trial (RCT) of pediatric Attention Deficit Hyperactivity Disorder (ADHD) patients using an experimental group and a control group. The subjects in the experimental group will be administered a commercially available pharmacogenomics (PGx) test panel of 38 genes specifically related to drug metabolism rates and drug response. A subset of these genes are known to be involved in the pharmacokinetics and pharmacodynamics of ADHD medications.

The PGx test report indicates if there are genetic variants detected related to ADHD medications and consequently provides recommendations for the clinician on which medications and doses may be optimally effective. The control group is the "treatment as usual" (TAU) group whose subjects are treated with medications for ADHD based on the treating clinician's customary method(s) for selecting medications and doses.

The hypotheses to be tested are that PGx testing guidance will reduce the time it takes to reach a treatment regimen that improves patient symptom relief, reduces the frequency and severity of adverse drug reactions, improves patient quality of life, and reduces parental emotional stress. Additionally, since the test is performed using next-generation sequencing, we wish to tabulate relevant allele frequencies and use variant call files to discover previously unknown PGx genetic variants.

Eligibility criteria: Inclusion Criteria:

* Male or female between the ages of 6 and 18 inclusive at the start of the study.
* Provision of signed and dated informed consent form.
* Subject and parent or legal guardian must state willingness to comply with all study procedures and availability for the duration of the study.
* Both male and female subjects will be recruited from the pediatric population diagnosed with any subtype of ADHD without Oppositional Defiant Disorder (ODD) via the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria.
* Subject and their parent or legal guardian will read and speak English with sufficient proficiency to understand the study and be able to give informed assent and consent.
* Subject will be able to complete study procedures such as filling out paper quality of life assessments
* Subjects will be able to take oral medication(s) if and as prescribed.
* Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria:

* Subjects will not have been treated for any condition with psychiatric prescription medications within the previous six (6) months.
* Subjects will not have had a diagnosis of Oppositional Defiant Disorder (ODD).
* Subject will not be currently a suicide risk, has previously made a suicide attempt or has a prior history of suicidal behavior.
* Subject will not have a history of alcohol or other substance abuse or dependence within the last 6 months.
* Subject will not have used an investigational medicinal product or participation in a clinical study within six (6) months prior to the baseline visit.
* Subject will not have a clinically important abnormality on urine drug and alcohol screen, if one had been taken.
* If the subject is female, is not currently pregnant, reasonably expecting to become pregnant, or lactating.
* Subject will not have a known or suspected allergy to any of the potential medications that may be prescribed.
* Only one subject per family will be enrolled to prevent systematic bias based on a parent or legal guardian's personal style of symptom assessment.

Primary outcomes:
measure: Assessment of Change in ADHD Symptom Severity Between Experimental and Control Group
timeFrame: At baseline and at 24 weeks
Secondary outcomes:
measure: Assessment of Differences in Parenting Stress Between Experimental and Control Group
timeFrame: At baseline and at 24 weeks
measure: Assessment of Differences in Child's Quality of Life Between Experimental and Control Group
timeFrame: At baseline and at 24 weeks
measure: Self-assessment of Differences in Child's Quality of Life Between Experimental and Control Group
timeFrame: At baseline and at 24 weeks
Other outcomes:
measure: PGx Allele Frequency Tabulation
timeFrame: 1 year from start of study
measure: Analysis of variant call files for genetic variants
timeFrame: 1 year from start of study
Locations:
city: Hamilton
country: United States
facility: Children's Specialized Hospital
state: New Jersey
city: Mountainside
country: United States
facility: Children's Specialized Hospital
state: New Jersey
city: Toms River
country: United States
facility: Children's Specialized Hospital
state: New Jersey
Study officials:
affiliation: Clinical and Translational Genome Research Institute, Inc.
name: Dan Handley, M.S., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Botkin JR, Belmont JW, Berg JS, Berkman BE, Bombard Y, Holm IA, Levy HP, Ormond KE, Saal HM, Spinner NB, Wilfond BS, McInerney JD. Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents. Am J Hum Genet. 2015 Jul 2;97(1):6-21. doi: 10.1016/j.ajhg.2015.05.022.
citation: Smith T, Sharp S, Manzardo AM, Butler MG. Pharmacogenetics informed decision making in adolescent psychiatric treatment: a clinical case report. Int J Mol Sci. 2015 Feb 20;16(3):4416-28. doi: 10.3390/ijms16034416.
citation: Olson MC, Maciel A, Gariepy JF, Cullors A, Saldivar JS, Taylor D, Centeno J, Garces JA, Vaishnavi S. Clinical Impact of Pharmacogenetic-Guided Treatment for Patients Exhibiting Neuropsychiatric Disorders: A Randomized Controlled Trial. Prim Care Companion CNS Disord. 2017 Mar 16;19(2). doi: 10.4088/PCC.16m02036.
citation: Gomez-Sanchez CI, Carballo JJ, Riveiro-Alvarez R, Soto-Insuga V, Rodrigo M, Mahillo-Fernandez I, Abad-Santos F, Dal-Re R, Ayuso C. Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects. Sci Rep. 2017 Sep 4;7(1):10391. doi: 10.1038/s41598-017-10912-y.
citation: Polanczyk G, Zeni C, Genro JP, Roman T, Hutz MH, Rohde LA. Attention-deficit/hyperactivity disorder: advancing on pharmacogenomics. Pharmacogenomics. 2005 Apr;6(3):225-34. doi: 10.1517/14622416.6.3.225.
citation: Myer NM, Boland JR, Faraone SV. Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD. Mol Psychiatry. 2018 Sep;23(9):1929-1936. doi: 10.1038/mp.2017.234. Epub 2017 Dec 12.
citation: Wehry AM, Ramsey L, Dulemba SE, Mossman SA, Strawn JR. Pharmacogenomic Testing in Child and Adolescent Psychiatry: An Evidence-Based Review. Curr Probl Pediatr Adolesc Health Care. 2018 Feb;48(2):40-49. doi: 10.1016/j.cppeds.2017.12.003. Epub 2018 Jan 8.