search
Back to results

Pharmacogenomics for Improving Pediatric ADHD Treatment

Primary Purpose

Attention Deficit Disorders With Hyperactivity

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Pharmacogenomics report
Sponsored by
Clinical and Translational Genome Research Institute, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Attention Deficit Disorders With Hyperactivity focused on measuring Attention Deficit Disorders with Hyperactivity, ADHD, Pharmacogenomics, Pediatric ADHD, ADHD medications

Eligibility Criteria

6 Years - 18 Years (Child, Adult)All SexesDoes not accept 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.

Sites / Locations

  • Children's Specialized Hospital
  • Children's Specialized Hospital
  • Children's Specialized Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Pharmacogenomics report

Control

Arm Description

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

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

Outcomes

Primary Outcome Measures

Assessment of Change in ADHD Symptom Severity Between Experimental and Control Group
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
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
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
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.

Full Information

First Posted
November 1, 2018
Last Updated
May 14, 2020
Sponsor
Clinical and Translational Genome Research Institute, Inc.
Collaborators
Children's Specialized Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT03730870
Brief Title
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

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Terminated
Why Stopped
This study's genetic testing laboratory has suspended operations pending discussions with the FDA concerning clinical interpretation of pharmacogenomics tests.
Study Start Date
February 28, 2019 (Actual)
Primary Completion Date
December 31, 2019 (Actual)
Study Completion Date
February 28, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Clinical and Translational Genome Research Institute, Inc.
Collaborators
Children's Specialized Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention Deficit Disorders With Hyperactivity
Keywords
Attention Deficit Disorders with Hyperactivity, ADHD, Pharmacogenomics, Pediatric ADHD, ADHD medications

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantOutcomes Assessor
Masking Description
Subjects will be blinded as to study arm participation and outcome assessments.
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pharmacogenomics report
Arm Type
Experimental
Arm Description
Clinician reviews pharmacogenomics report for subject prior to prescribing FDA-approved medications.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Clinician prescribes FDA-approved medications as customarily performed without additional guidance from pharmacogenomics report ("treatment-as-usual").
Intervention Type
Diagnostic Test
Intervention Name(s)
Pharmacogenomics report
Intervention Description
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.
Primary Outcome Measure Information:
Title
Assessment of Change in ADHD Symptom Severity Between Experimental and Control Group
Description
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.
Time Frame
At baseline and at 24 weeks
Secondary Outcome Measure Information:
Title
Assessment of Differences in Parenting Stress Between Experimental and Control Group
Description
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.
Time Frame
At baseline and at 24 weeks
Title
Assessment of Differences in Child's Quality of Life Between Experimental and Control Group
Description
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.
Time Frame
At baseline and at 24 weeks
Title
Self-assessment of Differences in Child's Quality of Life Between Experimental and Control Group
Description
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.
Time Frame
At baseline and at 24 weeks
Other Pre-specified Outcome Measures:
Title
PGx Allele Frequency Tabulation
Description
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.
Time Frame
1 year from start of study
Title
Analysis of variant call files for genetic variants
Description
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.
Time Frame
1 year from start of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Handley, M.S., Ph.D.
Organizational Affiliation
Clinical and Translational Genome Research Institute, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Specialized Hospital
City
Hamilton
State/Province
New Jersey
ZIP/Postal Code
08619
Country
United States
Facility Name
Children's Specialized Hospital
City
Mountainside
State/Province
New Jersey
ZIP/Postal Code
07092
Country
United States
Facility Name
Children's Specialized Hospital
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26140447
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. Erratum In: Am J Hum Genet. 2015 Sep 3;97(3):501.
Results Reference
background
PubMed Identifier
25710722
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.
Results Reference
background
PubMed Identifier
28314093
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.
Results Reference
background
PubMed Identifier
28871191
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.
Results Reference
background
PubMed Identifier
16013954
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.
Results Reference
background
PubMed Identifier
29230023
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.
Results Reference
background
PubMed Identifier
29325731
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.
Results Reference
background

Learn more about this trial

Pharmacogenomics for Improving Pediatric ADHD Treatment

We'll reach out to this number within 24 hrs