Pharmacogenomics for Improving Pediatric ADHD Treatment

Sponsor

Clinical and Translational Genome Research Institute, Inc. (Other)

Overall Status

Terminated

CT.gov ID

NCT03730870

Collaborator

Children's Specialized Hospital (Other)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Disorders With Hyperactivity	Diagnostic Test: Pharmacogenomics report	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Subjects will be blinded as to study arm participation and outcome assessments.

Primary Purpose:

Treatment

Official Title:

Assessment of Pharmacogenomics Testing for Improving Pediatric ADHD Psychopharmacological Treatment: A Randomized Controlled Trial

Actual Study Start Date :

Feb 28, 2019

Actual Primary Completion Date :

Dec 31, 2019

Actual Study Completion Date :

Feb 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pharmacogenomics report Clinician reviews pharmacogenomics report for subject prior to prescribing FDA-approved medications.	Diagnostic Test: Pharmacogenomics report Intervention is the performance of a pharmacogenomics laboratory-developed test (LDT) performed by high-throughput sequencing of 38 genes involved in drug pharmacokinetics or pharmacodynamics. The clinician reviews the report results for each subject.
No Intervention: Control Clinician prescribes FDA-approved medications as customarily performed without additional guidance from pharmacogenomics report ("treatment-as-usual").

Arm

Intervention/Treatment

Experimental: Pharmacogenomics report

Clinician reviews pharmacogenomics report for subject prior to prescribing FDA-approved medications.

Diagnostic Test: Pharmacogenomics report

Intervention is the performance of a pharmacogenomics laboratory-developed test (LDT) performed by high-throughput sequencing of 38 genes involved in drug pharmacokinetics or pharmacodynamics. The clinician reviews the report results for each subject.

No Intervention: Control

Clinician prescribes FDA-approved medications as customarily performed without additional guidance from pharmacogenomics report ("treatment-as-usual").

Outcome Measures

Primary Outcome Measures

Assessment of Change in ADHD Symptom Severity Between Experimental and Control Group [At baseline and at 24 weeks]
Measurement is performed by using the National Institute for Children's Health Quality (NICHQ) Vanderbilt Assessment Scales. The Vanderbilt assessment for ADHD is a validated questionnaire that provides a quantitative measure of ADHD symptoms and severity. Specific measures: Symptom Score: 18 questions on symptom type and severity between a measure of 0 (Never) and 3 (Very Often). Total Symptom Score range from 0 to 54. Lower scores indicate less severe symptoms. Performance Score: 8 questions on subject academic and interpersonal relationship functions using a measure between 1 (Excellent) and 5 (Problematic). Performance Score ranges from 0 to 40. Lower scores indicate better performance. Side Effects or Problems: 12 questions related to health and behavioral issues. Scores range from None, Mild, Moderate, to Severe. These are not quantitatively scored on the assessment. These measurements will be analyzed separately. This assessment is performed by parent/guardian.

Secondary Outcome Measures

Assessment of Differences in Parenting Stress Between Experimental and Control Group [At baseline and at 24 weeks]
Measurement is performed using the Psychological Assessment Resources (PAR) Parenting Stress Index - 4th edition - Short Form for Parents of Children (ages 6-10) or Stress Index for Parents of Adolescents (ages 11-18) as appropriate for age at time of enrollment. Questionnaire for children ages 6 - 10 consists of 36 questions regarding problems with parental stress. Scale for each question ranges from 1 (Strongly Agree) to 5 (Strongly Disagree). Total scoring ranges from 36 to 180. Higher scores indicate less parenting stress. Questionnaire for adolescents ages 11 - 18 consists of 90 questions regarding problems with parental stress. Scale for each question ranges from 1 (Strongly Agree) to 5 (Strongly Disagree). Total scoring ranges from 90 to 450. Higher scores indicate less parenting stress. Assessment performed by parent/guardian.
Assessment of Differences in Child's Quality of Life Between Experimental and Control Group [At baseline and at 24 weeks]
Measurement is performed using the PedsQL Pediatric Quality of Life Inventory Parent-Proxy Report for Children (ages 5-7, 8-12, 13-18). Questionnaire consists of 23 questions regarding problems with subject's physical, emotional, social, and school functioning. Scale for each question ranges from 0 (Never) to 4 (Almost Always). Total scoring ranges from 0 to 92. Lower scores indicate higher quality of life. Assessment is performed by parent/guardian.
Self-assessment of Differences in Child's Quality of Life Between Experimental and Control Group [At baseline and at 24 weeks]
Measurement is performed using the PedsQL Pediatric Quality of Life Inventory Child-Self Report (ages 5-7, 8-12, 13-18). Questionnaire consists of 23 questions regarding problems with subject's physical, emotional, social, and school functioning. Scale for each question ranges from 0 (Never) to 4 (Almost Always). Total scoring ranges from 0 to 92. Lower scores indicate higher quality of life. Assessment performed by subject.

Other Outcome Measures

PGx Allele Frequency Tabulation [1 year from start of study]
Tabulation of allele frequencies associated with the PGx genes that are sequenced. This is intended to add to current knowledge of how prevalent relevant alleles are in the population.
Analysis of variant call files for genetic variants [1 year from start of study]
Analysis of next-generation sequencing variant call files to determine whether the tests capture any previously unknown or undiscovered genetic variants, and assess their possible clinical significance.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Specialized Hospital	Hamilton	New Jersey	United States	08619
2	Children's Specialized Hospital	Mountainside	New Jersey	United States	07092
3	Children's Specialized Hospital	Toms River	New Jersey	United States	08755