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Pharmacogenetic-Guided Antidepressant Prescribing in Adolescents (PGx-GAP)

Primary Purpose

Depression in Adolescence

Status
Not yet recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Pharmacogenetic-guided dosing
GLAD-PC guided dosing
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression in Adolescence focused on measuring Depression, Adolescence, SSRI, Antidepressant, Pharmacogenetics

Eligibility Criteria

12 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 12-17 Depression as the primary concern, confirmed by the treating physician QIDS-A17 score greater than or equal to 11 indicating moderate-to-severe symptoms Prior failure of fluoxetine therapy due to inefficacy or intolerance Intention to start a new SSRI English fluency Exclusion Criteria: Co-occurring psychosis, bipolar disorder, eating disorder, autism spectrum disorder, fetal alcohol spectrum disorder, or intellectual disability A score of 2 or 3 on suicide item 13 of the QIDS-A17 High-risk alcohol or substance use (excluding cannabis and tobacco) as indicated by a score of monthly or more on the S2BI History of non-response to 3 or more antidepressants (including fluoxetine, i.e. failure of fluoxetine and two other agents) as confirmed by the treating physician Psychotherapy or brain stimulation-based therapy initiated within 8 weeks of referral, or plans to initiate/change these therapies during study participation History of liver or hematopoietic cell transplant History of CYP2B6, CYP2C19, or CYP2D6 testing

Sites / Locations

  • University of Calgary

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Pharmacogenetic (PGx)-Guided

Guidelines for Adolescent Depression in Primary Care (GLAD-PC)-Guided

Arm Description

Participants and their physician will receive a one-time prescribing report after completing baseline for second-line selective serotonin reuptake inhibitors with dosing information based on CYP2B6, CYP2C19, and CYP2D6 genotype data.

Participants and their physician will receive a one-time prescribing report after completing baseline for second-line selective serotonin reuptake inhibitors based on GLAD-PC dosing guidelines.

Outcomes

Primary Outcome Measures

Number of participants with depression remission
Quick Inventory of Depressive Symptomatology - Adolescent - 17-item (QIDS-A17) total score < 6. Scores range from 0-27, with higher scores indicative of more severe depression.

Secondary Outcome Measures

Number of participants with side effects and adverse drug reactions
Frequency, Intensity, Burden of Side Effects Rating (FIBSER) scale. Total scores range from 0-6 (3 items); cut-points are used to indicate moderate (score of 3) or severe (score of 5) adverse drug reaction/side effect interference with activities.
Percent Change in Role functioning
WHO Disability Assessment Schedule. Scores range from 0 to 48, with higher scores indicative of worse role functioning.
Percent Change in Depressive Symptom Severity
Quick Inventory of Depressive Symptomatology - Adolescent - 17-item (QIDS-A17). Scores range from 0-27, with higher scores indicative of more severe depression.
Percent Change in clinician assessment of depressive symptom severity
Change in Clinical Global Impression Severity (CGI-S) scale. Scores range from 0-7, with higher scores indicative of more severe illness.
Change in self-report health care resource use
Resource use questionnaire that captures number of visits and out-of-pocket costs for various mental health services.
Change in health care utilization
Administrative data will be obtained on medication information (agent, dose, duration) and health care utilization (doctor visits, hospitalizations, emergency room visits).
Change in health-related quality of life
EuroQoL 5 Dimension - Youth (EQ-5D-Y). Five descriptive items code level of perceived problems in health states and a visual analog scale has a score from 0-100, with higher scores indicative of better health.
Change in medication adherence
Medication Adherence Report Scale (MARS-5) scores. Scores range from 5-25 with higher scores indicative of better medication adherence.
Change in behavioral activation
Emergence of activation based on Treatment-Emergent Activation and Suicidality Assessment Profile. Total scores range from 0-114 (38 items) with higher scores indicating greater behavioral activation.

Full Information

First Posted
July 14, 2023
Last Updated
July 25, 2023
Sponsor
University of Calgary
Collaborators
University of Alberta
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1. Study Identification

Unique Protocol Identification Number
NCT05965401
Brief Title
Pharmacogenetic-Guided Antidepressant Prescribing in Adolescents
Acronym
PGx-GAP
Official Title
Pharmacogenetic-Guided Antidepressant Prescribing (PGx-GAP) in Adolescents
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
September 2027 (Anticipated)
Study Completion Date
December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary
Collaborators
University of Alberta

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a parallel arm randomized (1:1) controlled trial. Adolescents aged 12-17 years (n=452) that did not respond or tolerate first-line fluoxetine therapy will be randomly allocated to receive 12-weeks of pharmacogenetic-guided antidepressant therapy (experimental intervention) or GLAD-PC guided prescribing (control intervention).
Detailed Description
Goal: To test the efficacy of pharmacogenetic-guided antidepressant prescribing for adolescents with depression. Background: For an adolescent with moderate to severe depression, antidepressant medication is prescribed, often in combination with psychotherapy. The class of antidepressants recommended for use is selective serotonin reuptake inhibitors (SSRIs) with fluoxetine recommended as the first-line medication, and four other SSRIs recommended for consideration (sertraline, citalopram, escitalopram, fluvoxamine) if the adolescent does not respond or tolerate fluoxetine. For most adolescents, medication prescribing, and monitoring will be managed by a primary care physician or community pediatrician rather than by a mental health care provider, and guidelines exist to support this management (Guidelines for Adolescent Depression in Primary Care, GLAD-PC). However, GLAD-PC does not account for SSRI metabolism phenotypes that could change whether the SSRI selected is efficacious or tolerated. Our team of researchers, clinician scientists, patient partners, and primary care providers has designed a trial to test the impact of accounting for metabolism phenotypes, through pharmacogenetic-guided antidepressant prescribing, on adolescent outcomes, experiences, and health care utilization. Principal Question: Compared to GLAD-PC informed prescribing, does pharmacogenetic-guided prescribing for depressed adolescents who have not responded or tolerated first-line fluoxetine therapy, have superior efficacy following 12-weeks of therapy with an alternative SSRI? The Trial: This is a parallel arm randomized controlled trial. Adolescents aged 12-17 years (n=452) that did not respond or tolerate first-line fluoxetine therapy will be randomly allocated to receive pharmacogenetic-guided antidepressant therapy (experimental intervention) or GLAD-PC guided prescribing (control intervention). Participants and prescribing physicians will be blinded to which intervention was received. The primary outcome is depressive symptom remission at 12 weeks measured using the Quick Inventory of Depressive Symptomatology - Adolescent (17-item) (QIDS-A17). Secondary outcomes include side effects, role functioning, medication adherence, and health-related quality of life measured 4-, 8-, and 12-weeks after intervention initiation as well as cost-effectiveness.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression in Adolescence
Keywords
Depression, Adolescence, SSRI, Antidepressant, Pharmacogenetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This is a parallel arm randomized controlled trial.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants, their prescribing physician, and the investigator will all be blinded to study arm. The study coordinator will be the only one unblinded to study arm allocation.
Allocation
Randomized
Enrollment
452 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pharmacogenetic (PGx)-Guided
Arm Type
Experimental
Arm Description
Participants and their physician will receive a one-time prescribing report after completing baseline for second-line selective serotonin reuptake inhibitors with dosing information based on CYP2B6, CYP2C19, and CYP2D6 genotype data.
Arm Title
Guidelines for Adolescent Depression in Primary Care (GLAD-PC)-Guided
Arm Type
Active Comparator
Arm Description
Participants and their physician will receive a one-time prescribing report after completing baseline for second-line selective serotonin reuptake inhibitors based on GLAD-PC dosing guidelines.
Intervention Type
Other
Intervention Name(s)
Pharmacogenetic-guided dosing
Intervention Description
SSRI dosing based on Clinical Pharmacogenetics Implementation Consortium's SSRI dosing guidelines.
Intervention Type
Other
Intervention Name(s)
GLAD-PC guided dosing
Intervention Description
SSRI dosing based on GLAD-PC clinical practice guidelines
Primary Outcome Measure Information:
Title
Number of participants with depression remission
Description
Quick Inventory of Depressive Symptomatology - Adolescent - 17-item (QIDS-A17) total score < 6. Scores range from 0-27, with higher scores indicative of more severe depression.
Time Frame
Baseline to 12 weeks
Secondary Outcome Measure Information:
Title
Number of participants with side effects and adverse drug reactions
Description
Frequency, Intensity, Burden of Side Effects Rating (FIBSER) scale. Total scores range from 0-6 (3 items); cut-points are used to indicate moderate (score of 3) or severe (score of 5) adverse drug reaction/side effect interference with activities.
Time Frame
Baseline to 12 weeks
Title
Percent Change in Role functioning
Description
WHO Disability Assessment Schedule. Scores range from 0 to 48, with higher scores indicative of worse role functioning.
Time Frame
Baseline to 12 weeks
Title
Percent Change in Depressive Symptom Severity
Description
Quick Inventory of Depressive Symptomatology - Adolescent - 17-item (QIDS-A17). Scores range from 0-27, with higher scores indicative of more severe depression.
Time Frame
Baseline to 12 weeks
Title
Percent Change in clinician assessment of depressive symptom severity
Description
Change in Clinical Global Impression Severity (CGI-S) scale. Scores range from 0-7, with higher scores indicative of more severe illness.
Time Frame
Baseline to 12 weeks
Title
Change in self-report health care resource use
Description
Resource use questionnaire that captures number of visits and out-of-pocket costs for various mental health services.
Time Frame
Baseline to 12 weeks
Title
Change in health care utilization
Description
Administrative data will be obtained on medication information (agent, dose, duration) and health care utilization (doctor visits, hospitalizations, emergency room visits).
Time Frame
Baseline to 12 weeks
Title
Change in health-related quality of life
Description
EuroQoL 5 Dimension - Youth (EQ-5D-Y). Five descriptive items code level of perceived problems in health states and a visual analog scale has a score from 0-100, with higher scores indicative of better health.
Time Frame
Baseline to 12 weeks
Title
Change in medication adherence
Description
Medication Adherence Report Scale (MARS-5) scores. Scores range from 5-25 with higher scores indicative of better medication adherence.
Time Frame
4 to 12 weeks
Title
Change in behavioral activation
Description
Emergence of activation based on Treatment-Emergent Activation and Suicidality Assessment Profile. Total scores range from 0-114 (38 items) with higher scores indicating greater behavioral activation.
Time Frame
Baseline to 12 weeks
Other Pre-specified Outcome Measures:
Title
Minimally clinically important differences
Description
Participant-reported, Global Rating of Change Scale (GRCS) (11-point Likert scale ranging from +5 to -5) to indicate the degree to which symptoms and role functioning changed for the better, for the worse, or no change was experienced.
Time Frame
12 weeks
Title
Intervention fidelity
Description
Physician-reported, two-item questionnaire on use of recommendations in the dosing report.
Time Frame
12 weeks
Title
Blinding fidelity
Description
Physician-reported, 1-item survey about the perceived allocation of each of their participating patients; response options are 'PGx-guided prescribing', 'don't know' or 'GLAD-PC prescribing'
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 12-17 Depression as the primary concern, confirmed by the treating physician QIDS-A17 score greater than or equal to 11 indicating moderate-to-severe symptoms Prior failure of fluoxetine therapy due to inefficacy or intolerance Intention to start a new SSRI English fluency Exclusion Criteria: Co-occurring psychosis, bipolar disorder, eating disorder, autism spectrum disorder, fetal alcohol spectrum disorder, or intellectual disability A score of 2 or 3 on suicide item 13 of the QIDS-A17 High-risk alcohol or substance use (excluding cannabis and tobacco) as indicated by a score of monthly or more on the S2BI History of non-response to 3 or more antidepressants (including fluoxetine, i.e. failure of fluoxetine and two other agents) as confirmed by the treating physician Psychotherapy or brain stimulation-based therapy initiated within 8 weeks of referral, or plans to initiate/change these therapies during study participation History of liver or hematopoietic cell transplant History of CYP2B6, CYP2C19, or CYP2D6 testing
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laina McAusland, MSc
Phone
403-210-6353
Email
gap@ucalgary.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chad Bousman, PhD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Amanda Newton, PhD
Organizational Affiliation
University of Alberta
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized, individual participant PGx-GAP 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.

Learn more about this trial

Pharmacogenetic-Guided Antidepressant Prescribing in Adolescents

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