Investigating the Use of Genetics to Guide Pharmacologic Therapy for Hypertension

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Geneticure Panel for HTN therapy
* Drug: JNC-8


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with new diagnosis of hypertension or uncontrolled hypertension and on one medication Subject is able and willing to provide informed consent Subject is ≥ 30 and ≤ 80 years of age Subject with a Body Mass Index (BMI) ≥ 19 and ≤ 50 Exclusion Criteria: 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. Subject has clinically significant cardiac disease as determined by diagnosed coronary artery disease, diagnosed heart failure, and congenital cardiac disease. Subject has clinically significant vascular disease as determined by diagnosed peripheral vascular disease and diagnosed pulmonary hypertension. 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. Subject has secondary hypertension. Subject has prior diagnosis of endocrine disorders except uncomplicated type 2 diabetes and well controlled hypothyroidism. Subject is pregnant. Subject is breastfeeding. Subject becomes pregnant during study Subjects lacking the capacity to consent

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 |