Pharmacogenetic Testing for Optimizing Drug Therapy

(ToPP-UP Trial)

Overseen By Joshua N Terrell, MBA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Disqualifiers: Previous pharmacogenetic testing, Transplant, Dialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

492 Participants Needed

Trial Summary

What is the purpose of this trial?

This proposed research is relevant to human health because preemptive clinical pharmacogenetic testing may improve the personalization of drug therapy which should improve patient outcomes. Better understanding of the effectiveness and feasibility of preemptive clinical pharmacogenetic testing will inform when and how this innovative healthcare technology is implemented into clinical care. To ensure equitable dissemination in all patient populations, such data is also needed in racial minorities and other traditionally underserved populations. The combined proposed research are relevant to the parts of the NIH's mission pertaining to protecting and improving health and developing scientific human resources that will ensure the Nation's capability to prevent and treat disease.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It seems likely that you can continue your medications since the study involves optimizing drug therapy based on genetic testing.

What data supports the effectiveness of the treatment Panel-based pharmacogenetic genotyping?

Research shows that using a pharmacogenetic panel can help tailor drug treatments to individual genetic profiles, leading to better medication management and fewer adverse reactions. In one study, genetic testing led to changes in medication for about 32% of patients, showing its potential to improve treatment outcomes. ^{1 2 3 4 5}

Is pharmacogenetic testing safe for humans?

Pharmacogenetic testing, which helps tailor drug prescriptions based on a person's genetic makeup, has been shown to reduce adverse drug reactions (unwanted side effects) in patients. This suggests that it is generally safe and can improve the safety of drug therapy by preventing harmful reactions. ^{1 6 7 8 9}

How does pharmacogenetic testing optimize drug therapy?

Pharmacogenetic testing is unique because it uses a person's genetic information to predict how they will respond to certain drugs, allowing for personalized treatment plans. This approach can help prevent adverse drug reactions and improve the effectiveness of the therapy by tailoring it to the individual's genetic makeup, unlike traditional treatments that follow a one-size-fits-all model. ^{1 5 10 11 12}

Research Team

Julio Duarte, PharmD, PhD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for adults over 18 who take at least three prescription drugs and have had a medication change in the last 8 months due to various conditions like depression, heart issues, or chronic pain. It's not for those with past pharmacogenetic testing, organ transplants, kidney dialysis, or less than a year to live.

Inclusion Criteria

I've had a medication change or new diagnosis treatable with medication in the last 8 months.

I am older than 18 years.

I am currently taking three or more prescribed medications.

Exclusion Criteria

I am on chronic kidney dialysis.

I have had a stem cell or liver transplant from a donor.

I have had genetic testing for medication response.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Immediate panel-based pharmacogenetic genotyping

Subjects assigned to the immediate pharmacogenetic genotyping group will be tested and have their results both entered into their electronic health record as well as provided to them

2-4 weeks

1 visit (in-person)

Delayed panel-based pharmacogenetic genotyping

Subjects assigned to delayed panel-based pharmacogenetic genotyping will be tested, but their results will not be released until after their participation in the study has ended

12 months

1 visit (in-person)

Follow-up

Participants are monitored for changes in patient treatment satisfaction between baseline and 12 months after enrollment

12-14 months

Treatment Details

Interventions

• Panel-based pharmacogenetic genotyping

Trial Overview The study tests preemptive pharmacogenetic genotyping—a way to personalize drug therapy based on genetics—to see if it improves patient outcomes. It focuses on underserved groups including racial minorities to ensure broad benefits.

Participant Groups

Group I: Immediate panel-based pharmacogenetic genotyping Experimental Treatment 1 Intervention

Subjects assigned to the immediate pharmacogenetic genotyping group will be tested and have their results both entered into their electronic health record as well as provided to them within 2-4 weeks from enrollment.

Group II: Delayed panel-based pharmacogenetic genotyping Experimental Treatment 1 Intervention

Subjects assigned to delayed panel-based pharmacogenetic genotyping will be tested, but their results will not be released until after their participation in the study has ended (12 months after enrollment).

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Human Genome Research Institute (NHGRI)

Collaborator

Trials

273

Recruited

299,000+

Findings from Research

In a study involving 135 patients, pharmacogenetic (PGx) testing using a 16-gene panel identified at least one actionable variant in every participant, demonstrating its comprehensive utility in guiding medication choices.

PGx-guided recommendations led to changes in treatment for 32.4% of patients based on specific drug-gene interactions, highlighting the potential for personalized medicine to improve therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Relevance of a 16-Gene Pharmacogenetic Panel Test for Medication Management in a Cohort of 135 Patients. Niedrig, DF., Rahmany, A., Heib, K., et al.[2021]

Serious adverse drug reactions are a leading cause of death in the USA and contribute significantly to healthcare costs, highlighting the need for better risk management in drug prescriptions.

Pharmacogenomic testing, which identifies genetic factors that affect drug response, is becoming increasingly important, with regulatory agencies pushing for mandatory testing for certain medications to prevent adverse reactions and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenomics of adverse drug reactions: practical applications and perspectives. Becquemont, L.[2013]

A staggering 99% of veterans using VHA pharmacy services are projected to carry at least one actionable pharmacogenetic variant, indicating a high potential for personalized medicine to improve drug prescribing.

Over half of the veterans (54.8%) received at least one level A drug that could be influenced by these genetic variants, suggesting that pharmacogenetic testing could significantly impact treatment decisions for commonly prescribed medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Projected Prevalence of Actionable Pharmacogenetic Variants and Level A Drugs Prescribed Among US Veterans Health Administration Pharmacy Users. Chanfreau-Coffinier, C., Hull, LE., Lynch, JA., et al.[2020]

Pharmacogenomics helps explain why different people respond very differently to medications due to genetic variations in drug-metabolizing enzymes, transporters, and receptors.

By understanding these genetic differences, we can improve drug discovery and personalize treatments, potentially reducing the high rates of adverse drug reactions that contribute to significant health risks in the USA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in pharmacogenetics and pharmacogenomics. Vesell, ES.[2019]

References

1. Croatia pubmed.ncbi.nlm.nih.gov

Experience with comprehensive pharmacogenomic multi-gene panel in clinical practice: a retrospective single-center study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacogenomic Biomarkers for Improved Drug Therapy-Recent Progress and Future Developments. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Pharmacogenomic findings from clinical whole exome sequencing of diagnostic odyssey patients. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Relevance of a 16-Gene Pharmacogenetic Panel Test for Medication Management in a Cohort of 135 Patients. [2021]

5. England pubmed.ncbi.nlm.nih.gov

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Pharmacogenomics of adverse drug reactions: practical applications and perspectives. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Use of a multi-gene pharmacogenetic panel reduces adverse drug effects. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Projected Prevalence of Actionable Pharmacogenetic Variants and Level A Drugs Prescribed Among US Veterans Health Administration Pharmacy Users. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Advances in pharmacogenetics and pharmacogenomics. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Prediction of drug response and adverse drug reactions: From twin studies to Next Generation Sequencing. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Comparison of genome sequencing and clinical genotyping for pharmacogenes. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Pharmacogenomics in Cytotoxic Chemotherapy of Cancer. [2023]