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CompletedNCT03270891Updated Apr 11, 2023Results posted

Pharmacogenomic Testing in Primary Care

An interventional study of PGx test in Antidepressants Causing Adverse Effects in Therapeutic Use, sponsored by University of Michigan. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-04-11.

Sponsored by University of Michigan · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
75
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is a 6-month randomized, wait-listed, controlled pilot trial conducted in 6 department of family medicine (DFM) clinics at the University of Michigan (UM). Physicians practicing at a UM DFM clinical site who are willing to utilize pharmacogenomic (PGx) test results to manage antidepressant use will be enrolled. Patients of these DFM physicians who are adults with a new prescription for a target antidepressant will also be enrolled.

Read the detailed description

This is a 6-month randomized, wait-listed, controlled pilot trial conducted in 6 department of family medicine (DFM) clinics at the University of Michigan (UM). We will enroll physicians practicing at a UM DFM clinical site who are willing to utilize PGx test results in conjunction with treating patients prescribed certain antidepressants. We will also enroll patients of these DFM physicians who are adults with a new prescription for an antidepressant (within the past 4 weeks) including patients who have switched to a new antidepressant from another antidepressant or have added on a new antidepressant to current antidepressant therapy. Patients are excluded if taking an antidepressant for more than 4 weeks or if they have had PGx testing in the past. Patients will be randomized to either an intervention or control group. Patients in the intervention group will have PGx test results available soon after enrollment while the control patients will have test results available 3 months after the first visit. All patients will complete a baseline, 3-, and 6-month assessment; control patients will have an additional 9-month assessment. Data to be collected include symptoms and severity (PHQ-8, GAD7), functional health status (SF-12), PGx knowledge, work status changes, demographic information, physician and emergency department visits, adverse effects, and medication alterations and adherence.

02

Conditions studied

  • Antidepressants Causing Adverse Effects in Therapeutic Use

Keywords

  • Pharmacogenomics
  • Primary care physicians
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Physician participants

Inclusion criteria:

  • Be a practicing physician at a University of Michigan Department of Family Medicine clinic
  • Be willing to use PGx test results for their patients enrolled in the study
  • Be willing to allow study staff to contact their patients
  • Self-report that they are willing to prescribe antidepressants

Exclusion criteria:

-Do not meet inclusion criteria

Patient Participants

Inclusion:

  • Be a patient of a participating physician
  • Have a new prescription for one of the following antidepressant medications: citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Prozac Weekly, Rapiflux, Sarafem, Selfemra), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR), sertraline (Zoloft), duloxetine (Cymbalta, Irenka), venlafaxine (Effexor), venlafaxine XR (Effexor XR), nortriptyline (Aventyl, Pamelor), bupropion (Forfivo XL, Wellbutrin, Wellbutrin SR, Wellbutrin XL), mirtazapine (Remeron, Remeron Soltab), or vortioxetine (Trintellix)
  • Be willing to undergo PGx testing via single tube blood draw

Exclusion:

  • Do not speak English
  • Have previously undergone PGx testing
  • Are unable to provide their own consent to participate in the study
  • Have been taking the new antidepressant prescription for longer than 4 weeks (prior to screening)
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
75 participants (actual)

Study arms

  • Active comparator
    Delayed intervention (control arm)

    Patients in this arm will have PGx test results made available to physicians 3 months after study enrollment

    Diagnostic Test: PGx test

  • Experimental
    PGx Test

    Patients in this arm will have PGx test results made available to physicians as soon available after enrollment.

    Diagnostic Test: PGx test

Interventions

  • Diagnostic testPGx test

    A laboratory developed genetic test that differentiates common and uncommon alleles in genes that have been previously identified as being involved in either the metabolism or response of drugs used in the treatment of depression and/or anxiety. The results are provided as a report that contains information related to the allele status of the patient's genes, translates this into a phenotype, and relates this phenotype to recommendation classes for drugs.

    Also known as: Pharmacogenomic test, Progenity Informed PGx test

05

What researchers measure

Primary outcomes

  1. Count of Participants Prescribed Antidepressant Medication

    Count of participants who have been prescribed antidepressant medications which are not contraindicated

    Time frame: Baseline, 3 months, 6 months, and 9 months

Secondary outcomes

  1. Change in Symptom Severity - Patient Health Questionnaire (PHQ-8)

    Change in PHQ-8 scores. The PHQ-8 is an 8-item participant-report measure for screening for depression and for establishing depression severity. The total score ranges from 0-24, with a higher score indicating greater depression symptom severity.

    Time frame: Baseline and 6 months

  2. Change in Symptom Severity - General Anxiety Disorder - 7 (GAD 7)

    The GAD-7 is a self-administered assessment for general anxiety disorder. The total score for the seven items ranges from 0 to 21. Higher values represent a worse outcome.

    Time frame: Baseline and 6 months

  3. Change in Adherence to Refills and Medication Scale (ARMS) Scores

    Change in medication adherence: The Adherence to Refills and Medication was scored by summing together the 14 items after first reversing the final item to be consistent in direction with the others. Individuals were allowed to have up to 2 missing values present which were imputed with the mean of the remaining answered items, only a handful of individuals answered 13 of the 14 questions resulting in a single item within their scale being imputed across the time periods. The questionnaire has 14 items with each item being recorded on a four-point Likert scale. The total score ranges from 14-56 with the lower score indicating better adherence.

    Time frame: Baseline and 6 months

Other outcomes

  1. Acceptability of PGx Testing

    Acceptability of PGx testing in primary care among persons taking a target antidepressant and primary care physicians who care for them

    Time frame: Baseline and 6 months

06

Results

Posted Apr 11, 2023

Participant flow

Participant flow — Overall Study
MilestoneDelayed Intervention (Control Arm)PGx TestPhysicians
Started262524
Received intervention25250
For physician arm only; those physicians who had patients who participated0017
Completed221917
Not completed467
Withdrew: Lost to follow-up360
Withdrew: Withdrawal by subject100
Withdrew: For physician arm only; those physicians who did not have patients who participated007

Outcome measures

PrimaryCount of Participants Prescribed Antidepressant Medication

Count of participants who have been prescribed antidepressant medications which are not contraindicated

Time frame:
Baseline, 3 months, 6 months, and 9 months
Reported as:
Count of participants · Participants
Count of Participants Prescribed Antidepressant Medication
ParticipantsDelayed Intervention (Control Arm)PGx Test
Baseline58
Month 358
Month 668
Month 95—
SecondaryChange in Symptom Severity - Patient Health Questionnaire (PHQ-8)

Change in PHQ-8 scores. The PHQ-8 is an 8-item participant-report measure for screening for depression and for establishing depression severity. The total score ranges from 0-24, with a higher score indicating greater depression symptom severity.

Time frame:
Baseline and 6 months
Reported as:
Mean · score on a scale
Change in Symptom Severity - Patient Health Questionnaire (PHQ-8)
score on a scaleDelayed Intervention (Control Arm)PGx Test
Baseline9.0 ± 4.48.6 ± 6.1
6 month7.5 ± 4.35.8 ± 5.4
Statistical analysis
  • Delayed Intervention (Control Arm) · t-test, 2 sided · p = 0.0115
  • PGx Test · t-test, 2 sided · p = 0.027
SecondaryChange in Symptom Severity - General Anxiety Disorder - 7 (GAD 7)

The GAD-7 is a self-administered assessment for general anxiety disorder. The total score for the seven items ranges from 0 to 21. Higher values represent a worse outcome.

Time frame:
Baseline and 6 months
Reported as:
Mean · score on a scale
Change in Symptom Severity - General Anxiety Disorder - 7 (GAD 7)
score on a scaleDelayed Intervention (Control Arm)PGx Test
baseline9.1 ± 6.26.9 ± 5.6
Month 66.1 ± 5.05.2 ± 4.9
Statistical analysis
  • Delayed Intervention (Control Arm) · t-test, 2 sided · p = 0.0327
  • PGx Test · t-test, 2 sided · p = 0.2088
SecondaryChange in Adherence to Refills and Medication Scale (ARMS) Scores

Change in medication adherence: The Adherence to Refills and Medication was scored by summing together the 14 items after first reversing the final item to be consistent in direction with the others. Individuals were allowed to have up to 2 missing values present which were imputed with the mean of the remaining answered items, only a handful of individuals answered 13 of the 14 questions resulting in a single item within their scale being imputed across the time periods. The questionnaire has 14 items with each item being recorded on a four-point Likert scale. The total score ranges from 14-56 with the lower score indicating better adherence.

Time frame:
Baseline and 6 months
Reported as:
Mean · score on a scale
Change in Adherence to Refills and Medication Scale (ARMS) Scores
score on a scaleDelayed Intervention (Control Arm)PGx Test
baseline17.1 ± 3.317.4 ± 3.2
6 month17 ± 2.516.6 ± 3.2
Statistical analysis
  • Delayed Intervention (Control Arm) · t-test, 2 sided · p = 0.947
Other pre-specifiedAcceptability of PGx Testing

Acceptability of PGx testing in primary care among persons taking a target antidepressant and primary care physicians who care for them

Time frame:
Baseline and 6 months

Results for this outcome have not been posted.

Adverse events

Collected over six months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Delayed Intervention (Control Arm)0/26 (0%)0/26 (0%)0/26 (0%)
PGx Test0/25 (0%)0/25 (0%)0/25 (0%)

Baseline characteristics

1 participant was withdrawn by the study staff and PI after baseline data was collected but before receiving the intervention.

Age, Continuous
Age, Continuous(years)Delayed Intervention (Control Arm)PGx TestPhysiciansTotal
Mean39.2 ± 13.242.0 ± 14.6—40.5 ± 13.9
Sex/Gender, Customized
Sex/Gender, Customized(Participants)Delayed Intervention (Control Arm)PGx TestPhysiciansTotal
Male1310831
Female13141643
Other0101
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Delayed Intervention (Control Arm)PGx TestPhysiciansTotal
White23191961
Black1102
Asian1135
Other0224
Unknown1203
Region of Enrollment
Region of Enrollment(Participants)Delayed Intervention (Control Arm)PGx TestPhysiciansTotal
United States26252475
Marital Status
Marital Status(Participants)Delayed Intervention (Control Arm)PGx TestPhysiciansTotal
Not Married1510—25
Married1115—26
Education
Education(Participants)Delayed Intervention (Control Arm)PGx TestPhysiciansTotal
<4 yrs College811019
Bachelor's Degree76013
Graduate1182443
Employment
Employment(Participants)Delayed Intervention (Control Arm)PGx TestPhysiciansTotal
Unemployed78015
Employed19172460
Income
Income(Participants)Delayed Intervention (Control Arm)PGx TestPhysiciansTotal
<50k78—15
50k-99k107—17
100k+910—19

3 further baseline measures are reported on the registry.

07

Study locations

1 site
  • University of Michigan
    Ann Arbor, Michigan 48109, United States
08

References and documents

Publications

  • Manzor Mitrzyk B, Kadri R, Farris KB, Ellingrod VL, Klinkman MS, Ruffin Iv MT, Plegue MA, Buis LR. Using Pharmacogenomic Testing in Primary Care: Protocol for a Pilot Randomized Controlled Study. JMIR Res Protoc. 2019 Aug 19;8(8):e13848. doi: 10.2196/13848. PubMed 31429417 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 7, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03270891
Lead sponsor
University of Michigan
Responsible party
Lorraine Buis (Assistant Professor, Family Medicine Assistant Professor of Information, School of Information, University of Michigan) — Principal investigator
First posted
Sep 1, 2017
Start date
Dec 1, 2017
Primary completion
Sep 5, 2021
Completion
May 6, 2022
Results posted
Apr 11, 2023
Last update
Apr 11, 2023

Study contacts

Lorriane Buis, PhD
principal investigator · University of Michigan Department of Family Medicine

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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