Pharmacogenomics for Improving Pediatric ADHD Treatment

NCT03730870 | Terminated FDA Device

• 1 other identifier: 2018-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

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.

Conditions

Attention Deficit Disorders With Hyperactivity

Keywords

Attention Deficit Disorders with Hyperactivity; ADHD; Pharmacogenomics; Pediatric ADHD; ADHD medications

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Assessment of Differences in Parenting Stress Between Experimental and Control Group

  At baseline and at 24 weeks

• Assessment of Differences in Child's Quality of Life Between Experimental and Control Group

  At baseline and at 24 weeks

• Self-assessment of Differences in Child's Quality of Life Between Experimental and Control Group

  At baseline and at 24 weeks

Other Outcomes (2)

• PGx Allele Frequency Tabulation

  1 year from start of study

• Analysis of variant call files for genetic variants

  1 year from start of study

Study Arms (2)

Pharmacogenomics report

EXPERIMENTAL

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

Diagnostic Test: Pharmacogenomics report

Control

NO INTERVENTION

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

Interventions

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.

Pharmacogenomics report

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Clinical and Translational Genome Research Institute, Inc.: lead
• Children's Specialized Hospital: collaborator

Study Sites (3)

Children's Specialized Hospital

Hamilton, New Jersey, 08619, United States

Location

Children's Specialized Hospital

Mountainside, New Jersey, 07092, United States

Location

Children's Specialized Hospital

Toms River, New Jersey, 08755, United States

Location

Related 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.

  PMID: 26140447 BACKGROUND

• 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.

  PMID: 25710722 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.

  PMID: 28314093 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.

  PMID: 28871191 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.

  PMID: 16013954 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.

  PMID: 29230023 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.

  PMID: 29325731 BACKGROUND

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Dan Handley, M.S., Ph.D.

  Clinical and Translational Genome Research Institute, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Subjects will be blinded as to study arm participation and outcome assessments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Scientific Officer

Model Details: 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.

Study Record Dates

• First Submitted: November 1, 2018
• First Posted: November 5, 2018
• Study Start: February 28, 2019
• Primary Completion: December 31, 2019
• Study Completion: February 28, 2020
• Last Updated: May 18, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)