Investigating the Use of Genetics to Guide Pharmacologic Therapy for Hypertension (PGEN for HTN)

Prospective Randomized Controlled Trial Investigating the Use of Genetic Predisposition to Guide Pharmacologic Therapy for Hypertension

Hypertension is one of the most important preventable contributors to disease and death in the United States and represents the most common condition seen in the primary care setting. Approximately 78 million adults living in the U.S. have hypertension with more than 5 million new diagnoses made each year. Unfortunately, despite a significant impulse in the medical community to move towards an "individualized medicine" approach to patient centered treatment, the current clinical treatment strategy is based on a set algorithm which does not take into account individual patient differences. As a result hypertension is often sub-optimally treated based on "population averages", rather than a person's genetic make-up, with significant burden on our health care system. In fact, 40% of patients who are adherent to their blood pressure therapy (taking their medicines as prescribed by their clinician) do not have their blood pressure under control. Previous work has demonstrated significant functional polymorphisms within the kidney, vessels, and heart that will likely predict a patient's response to blood pressure pharmacotherapy. Previous work by our group, utilizing a retrospective design, has determined that the addition of genetic knowledge to prescribing can improve therapeutic guidance and decrease the time to blood pressure control significantly. Despite this, to date, there are no prospective trials to guide blood pressure therapy using multiple organ systems that are important in the three most common classes of drugs: diuretics, vasodilators, and beta-blockers. The objective of this clinical trial is to determine the efficacy of genetically guided therapeutic options for pharmacologic treatment of essential hypertension in newly diagnosed patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension
• Intervention / Treatment: Drug: Geneticure Panel for HTN therapy; Drug: JNC-8

Detailed Description

Specific Aim:

To determine the efficacy of genetically guided therapeutic options for pharmacologic treatment of essential hypertension, when compared to conventional standard of care (JNC 8 guideline directed therapy).

Hypothesis A: Patients randomized to genetically guided blood pressure therapy will have significantly reduced time to optimal blood pressure control compared to conventional standard of care.

Hypotheses B: Patients randomized to genetically guided blood pressure therapy will have significantly greater absolute blood pressure reduction compared to conventional standard of care.

Hypothesis C: Patients randomized to genetically guided blood pressure therapy will have to take fewer classes of blood pressure medicines in order to achieve blood pressure control.

Secondary Aim:

To determine if genetically guided blood pressure therapy reduces number of medication changes in patients with hypertension.

Hypotheses: Patients randomized to genetically guided blood pressure therapy will have significantly less medication changes.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eric M Snyder, PhD; Phone Number: 702 18003628109; Email: eric@geneticure.com
• Study Contact Backup: Name: Thomas P Olson, PhD; Phone Number: 703 18003628109; Email: tom@geneticure.com

Study Locations

• United States
  • Minnesota
    • Andover, Minnesota, United States, 55304
      • Fairview Health Clinics - Andover
    • Blaine, Minnesota, United States, 55449
      • Fairview Health Clinics - Blaine
    • Bloomington, Minnesota, United States, 55420
      • Fairview Health Clinics - Bloomington, Oxboro
    • Brooklyn Park, Minnesota, United States, 55443
      • Fairview Clinics - Brooklyn Park
    • Burnsville, Minnesota, United States, 55337
      • Fairview Clinics- Burnsville
    • Columbia Heights, Minnesota, United States, 55421
      • Fairview Clinics - Columbia Heights
    • Edina, Minnesota, United States, 55345
      • Fairview Health Clinics - Edina
    • Elk River, Minnesota, United States, 55330
      • Fairview Health Clinics - Elk River
    • Fridley, Minnesota, United States, 55432
      • Fairview Clinics - Fridley
    • Lino Lakes, Minnesota, United States, 55014
      • Fairview Clinics - Lino Lakes
    • Minneapolis, Minnesota, United States, 55406
      • Fairview Clinics - Hiawatha
    • N. Branch, Minnesota, United States, 55056
      • Fairview Clinics - North Branch
    • New Brighton, Minnesota, United States, 55112
      • Fairview Clinic - New Brighton
    • Wyoming, Minnesota, United States, 55092
      • Fairview Clinics - Wyoming
    • Zimmerman, Minnesota, United States, 55398
      • Fairview Health Services - Zimmerman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject with new diagnosis of hypertension or uncontrolled hypertension and on one medication
2. Subject is able and willing to provide informed consent
3. Subject is ≥ 30 and ≤ 80 years of age
4. Subject with a Body Mass Index (BMI) ≥ 19 and ≤ 50

Exclusion Criteria:

1. Subject has been diagnosed with chronic kidney disease as determined by serum creatinine levels of >1.3 mg/dl for men and >1.1 for women.
2. Subject has clinically significant cardiac disease as determined by diagnosed coronary artery disease, diagnosed heart failure, and congenital cardiac disease.
3. Subject has clinically significant vascular disease as determined by diagnosed peripheral vascular disease and diagnosed pulmonary hypertension.
4. Liver dysfunction is defined using the normal reference range for lower limit of normal and upper limit of normal used by Fairview labs and as determined by diagnosed liver disease /cirrhosis as listed in the patient's problem list based on ICD-10.
5. Subject has secondary hypertension.
6. Subject has prior diagnosis of endocrine disorders except uncomplicated type 2 diabetes and well controlled hypothyroidism.
7. Subject is pregnant.
8. Subject is breastfeeding.
9. Subject becomes pregnant during study
10. Subjects lacking the capacity to consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genetically-Guided Treatment for HTN; Using a patient's genetic composition to guide BP prescribing for patients with hypertension, post diagnosis.	Drug: Geneticure Panel for HTN therapy; Using either Genetics (Geneticure for HTN multi-gene panel) or JNC-8 guidelines for prescribing for patients with hypertension
Active Comparator: JNC-8-Guided Treatment; Using traditional (JNC-8) guidelines for BP prescribing for patients with hypertension, post diagnosis.	Drug: JNC-8; Using JNC-8 guidelines to guide therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Blood Pressure Control	Time to BP control between genetically-guided prescribing and JNC-8 guided prescribing	1 year
Change in Blood Pressure	Change (absolute) in BP (systolic, SBP, diastolic, DBP, and mean arterial, MAP) between genetically-guided prescribing and JNC-8 guided prescribing	1 year
Number of Blood Pressure Medicines	Number of blood pressure medicines needed to obtain control of hypertension between genetically-guided prescribing and JNC-8 guided prescribing	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Medication Changes	Number of blood pressure medicine changes needed to obtain control of hypertension between genetically-guided prescribing and JNC-8 guided prescribing	1 year

Collaborators and Investigators

• Sponsor: Geneticure, LLC
• Collaborators: University of Minnesota; Fairview Health Services
• Investigators: Principal Investigator: Pamela Phelps, PharmD, Fairview Health Services; Study Director: Weihong Tang, MD, PhD, University of Minnesota; Principal Investigator: Michael Schulenberg, MD, Fairview Health Services

Publications and helpful links

Helpful Links

• Sponsor Site

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2022
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: December 7, 2016
• First Submitted That Met QC Criteria: December 7, 2016
• First Posted (Estimate): December 9, 2016

Study Record Updates

• Last Update Posted (Actual): February 2, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: Geneticure

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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