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This study's genetic testing laboratory has suspended operations pending discussions with the FDA concerning clinical interpretation of pharmacogenomics tests.
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| Name | Class |
|---|---|
| Children's Specialized Hospital | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pharmacogenomics report | Experimental | Clinician reviews pharmacogenomics report for subject prior to prescribing FDA-approved medications. |
|
| Control | No Intervention | Clinician prescribes FDA-approved medications as customarily performed without additional guidance from pharmacogenomics report ("treatment-as-usual"). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pharmacogenomics report | Diagnostic Test | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At baseline and at 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| PGx Allele Frequency Tabulation | 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. | 1 year from start of study |
| Analysis of variant call files for genetic variants |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dan Handley, M.S., Ph.D. | Clinical and Translational Genome Research Institute, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Specialized Hospital | Hamilton | New Jersey | 08619 | United States | ||
| Children's Specialized Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26140447 | Background | 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. | |
| 25710722 | Background |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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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.
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Subjects will be blinded as to study arm participation and outcome assessments.
|
| At baseline and at 24 weeks |
| 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. | At baseline and at 24 weeks |
| 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. | At baseline and at 24 weeks |
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. |
| 1 year from start of study |
| Mountainside |
| New Jersey |
| 07092 |
| United States |
| Children's Specialized Hospital | Toms River | New Jersey | 08755 | United States |
| 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. |
| 28314093 | Background | 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. |
| 28871191 | Background | 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. |
| 16013954 | Background | 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. |
| 29230023 | Background | 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. |
| 29325731 | Background | 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. |