Pharmacogenomics for Improving Pediatric ADHD Treatment

Attention Deficit Disorders With Hyperactivity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03730870
• Other study ID #: 2018-01
• Status: Terminated
• Phase: N/A
• Start date: February 28, 2019
• Est. completion date: February 28, 2020

Study information

• Verified date: May 2020
• Source: Clinical and Translational Genome Research Institute, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: February 28, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Disorders With Hyperactivity
• Hyperkinesis

Intervention

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.

Locations

Country	Name	City	State
United States	Children's Specialized Hospital	Hamilton	New Jersey
United States	Children's Specialized Hospital	Mountainside	New Jersey
United States	Children's Specialized Hospital	Toms River	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Clinical and Translational Genome Research Institute, Inc.	Children's Specialized Hospital

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. Review. Erratum in: Am J Hum Genet. 2015 Sep 3;97(3):501. — View Citation

Gomez-Sanchez CI, Carballo JJ, Riveiro-Alvarez R, Soto-Insuga V, Rodrigo M, Mahillo-Fernandez I, Abad-Santos F, Dal-Ré 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. — View 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. — View 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. — View 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. Review. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Analysis of variant call files for genetic variants	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
Primary	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
Secondary	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.	At baseline and at 24 weeks
Secondary	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
Secondary	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