Pharmacogenomics of Stimulant Treatment Response (PGx-STaR)

Pharmacogenomics of Stimulant Treatment Response in Children and Adolescents With Attention-Deficit/ Hyperactivity Disorder

The "Pharmacogenomics of Stimulant Treatment Response" (PGx-STaR) study aims to identify genetic profiles related to methylphenidate treatment outcomes in children and adolescents aged 6-24 with Attention deficit/hyperactivity disorder (ADHD).

Study Overview

• Status: Recruiting
• Conditions: Attention-Deficit/ Hyperactivity Disorder (ADHD)

Detailed Description

Background: ADHD is a common neurodevelopmental disorder affecting children and adolescents, with psychostimulants, specifically slow-release methylphenidate (e.g., Biphentin®, Concerta®), being a first-line treatment option. However, the response to medications varies significantly among individuals, with some experiencing limited benefits or intolerable side effects. Unlike other areas of psychiatry, ADHD pharmacotherapy lacks genetic markers to guide treatment decisions, resulting in delayed symptom relief and diminished quality of life for patients.

Objectives:

1. Identifying genomic profiles associated with psychostimulant treatment response and tolerability in children and adolescents with ADHD.
2. Establishing a research platform for the discovery of new genetic and non-genetic markers of drug treatment outcomes relevant to mental health care in children.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Madison Heintz, MSW; Phone Number: 5875739747; Email: psychpgxlab@ucalgary.ca
• Study Contact Backup: Name: Weng-Sam Siu, MSPT, MSc; Phone Number: 5875739747; Email: sam.siu@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • University of Calgary
      • Contact: Madison Heintz, MSW; Phone Number: 5875739747; Email: psychpgxlab@ucalgary.ca
      • Principal Investigator: Chad Bousman, MPH, PhD
      • Sub-Investigator: Kara Murias, MD, PhD
      • Sub-Investigator: Paul Arnold, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children and adolescent with primary diagnosis of ADHD (all types), aged 6-24 years.

Description

Inclusion Criteria:

Patients will be eligible for participation if all the following are true.

• Aged 6 - 24 years.
• Located in Western Canada (i.e., Alberta, British Columbia, Saskatchewan, Manitoba).
• Primary diagnosis of ADHD (all types).
• Starting Methylphenidate (excluding immediate release forms) treatment.

Exclusion Criteria:

Patients will be excluded from participation if any of the following are true.

• Co-occurring psychotic, bipolar or eating disorders.
• Significant risk of suicide.
• An intellectual disability, or diagnosis of autism spectrum disorder (ASD) or tics/Tourette disorders.
• Past 12-month high-risk alcohol or substance use defined as monthly or more frequent use.
• Psychotherapy or brain stimulation-based therapy initiated within 8 weeks of referral or plans to initiate/change these types of therapies during the study
• History of liver or bone marrow (hematopoietic cell) transplant as these events can result in ambiguous genomic results.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ADHD symptom severity	Strengths and Weaknesses of Attention-Deficit/Hyperactivity Symptoms and Normal Behavior Scale (SWAN) Rating Scale for ADHD. Score range = -90 to +90, with higher scores indicative of worse outcome.	Baseline and 1, 2, 3, and 4 weeks post-baseline
Side effect frequency and severity	CADDRA ADHD Medication and Side Effect Form	1, 2, 3, and 4 weeks post-baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Methylphenidate/ritalinic acid exposure	Methylphenidate and ritalinic acid trough plasma levels	4 weeks post-baseline
Change in working memory	Sorting Working Memory Test (7 minutes; administered orally and online with research team member). An assessment of working memory. A participant is asked to recall and sequence different stimuli that are presented visually and via audio. Higher scores indicate better outcome.	Baseline and 4 weeks post-baseline
Change in attention	Dimension Change Card Sort Test (8 minutes; administered online). An assessment of cognitive flexibility and attention. A participant is asked to match a series of picture pairs to a target picture. Higher scores indicate better outcome.	Baseline and 4 weeks post-baseline
Change in inhibitory control	Flanker Inhibitory Control and Attention Test (7 minutes; administered online). An assessment of inhibitory control and attention. A participant is asked to focus on a particular stimulus while inhibiting attention to the stimuli flanking it. Higher scores indicate better outcome.	Baseline and 4 weeks post-baseline
Change in impulse control	Stop Signal Task (10 minutes; administered online). An assessment of impulse control. A participant is presented with a target stimulus and are asked to respond to the stimulus as fast as possible. Higher score indicate better outcome.	Baseline and 4 weeks post-baseline
Change in functioning	Columbia Impairment Scale. Score range 0-52, with higher scores indicative of worse outcome.	Baseline and 4 weeks post-baseline
Change in child quality of life	Pediatric Quality of Life Inventory (PedsQoL). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better quality of life.	Baseline and 4 weeks post-baseline
Change in carer quality of life	Care-related Quality of Life instrument (Carer QoL-7D). Utility tariffs for the CarerQol have been developed to calculate a CarerQol-7D utility score from the responses on the seven dimensions, ranging between 0 ('worst imaginable caregiving situation') and 100 ('best imaginable caregiving situation'). Higher utility scores thus reflect better care-related quality of life.	Baseline and 4 weeks post-baseline

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Chad Bousman, MPH, PhD, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: January 14, 2024
• First Posted (Actual): January 24, 2024

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Adolescents; Children; ADHD; Pharmacogenetics; Methylphenidate; Neurology; Psychostimulants
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity
• Other Study ID Numbers: REB23-0366

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Anonymized, individual participant PGx-STaR data will be shared using a controlled-access model. Under this model, the data will be released to a researcher if access criteria are met.

All requests for data sharing should be made to the Co-Principal Investigators who will be responsible for reviewing and granting requests. Requestors should provide a research proposal for review. In the event that a data sharing request is declined, reasons will be provided to the requestor. If the data sharing request is granted, a data-sharing agreement will be initiated by the Co-Principal Investigators alongside the University of Calgary (lead institution). This agreement will include information on the individual data to be shared; if other documents will be available (e.g., statistical codes, data dictionary), when the data will be available and for how long, and how data access will be provided (e.g., file transfer).

• IPD Sharing Access Criteria: The requestor is affiliated with an academic institution as an independent investigator or trainee of an independent investigator;; The proposed research question(s) and hypothesis(es) are specific, measurable, and achievable;; The proposed research project will be governed/overseen by a local legal/regulatory body;; The proposed research project poses no risk of invasion of privacy or breaches of confidentiality for trial participants;; A member of the proposed research team has sufficient statistical skills to carry out the proposed analytic plan;; The requestor has sufficient financial and/or human resources to see the proposed research project to completion;; The proposed research question(s) and hypothesis(es) do not conflict with active or planned studies of the Co-Principal Investigators.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No