Proteus Discover in Subjects With Uncontrolled Hypertension and Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy of a new digital health offering, Proteus Discover to lower blood pressure and glycated hemoglobin in patients with uncontrolled hypertension and type 2 diabetes.

Detailed Description
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Cardiometabolic diseases as defined in this protocol refer to diseases that increase risk for cardiovascular disease. Proteus® Digital Health is operationally defining cardiometabolic (CMB) conditions for this study as including hypertension, type 2 diabetes, and hypercholesterolemia. The prevalence of metabolic diseases is growing. Factors contributing to this rise include the obesity epidemic and the aging population. In particular, because of the costs and risk of complications associated with diabetes and hypertension, many health systems and payers are increasing focus on interventions to reduce the burden of these diseases. The purpose of the study was to evaluate the ability of a new digital health offering, Proteus Discover to lower blood pressure and glycated hemoglobin in patients with uncontrolled hypertension and type 2 diabetes. The study enrolled subjects with uncontrolled hypertension and type 2 diabetes failing at least 2 antihypertensives and metformin and/or a sulfonylurea. Subjects were randomized to one of 3 arms: use of Proteus Discover for 4 weeks, use of Proteus Discover for 12 weeks, or usual care. Subjects randomized to the intervention arms, used a digital health offering to (1) provide automatic and passive electronic documentation of medication adherence and patterns of medication taking, (2) assist providers in distinguishing inadequate medication adherence or pharmacologic unresponsiveness as the root cause for uncontrolled hypertension and type 2 diabetes, and (3) inform management decisions (dose adjustment, medication addition or substitution, adherence counseling, referral to a hypertension specialist). Subjects randomized to usual care, received usual medical care such as medication changes, adherence counseling, and lifestyle coaching. Providers could also schedule additional visits without restrictions.

Official Title
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Use of Proteus Discover to Enable Improved Clinical Outcomes in Subjects With Uncontrolled Hypertension and Type 2 Diabetes Mellitus: A Pilot Study

Conditions
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Hypertension, Diabetes Mellitus, Type 2, Hypercholesterolemia

Intervention / Treatment
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* Other: Proteus Discover
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (18 to 75 years old) who are diagnosed with essential hypertension and type 2 diabetes mellitus with or without hypercholesterolemia (defined as taking statin therapy). Both hypertension and diabetes are suboptimally controlled at Screening: SBP is ≥ 140 mm Hg (and his/her BP goal is < 140/90 mm Hg). A1C is ≥ 7% and ≤ 11% at Screening (A1C is above goal by ≥ 0.5%). On a stable anti-hypertensive regimen (on current regimen for at least 30 days) with at least 2 anti-hypertensive medications Ability to manage the subject during the 12-week study with anti-hypertensive medication(s) and dose forms (or same drug classes and comparable doses for Usual Care subjects) used within the study. Currently on metformin and/or glipizide for diabetes for at least the past 60 days prior to Screening. Subjects can be managed on other noninsulin diabetes medicines (including sulfonylureas other than glipizide) during the study. Subjects must have a Proteus test pill (IS used to test that the Proteus Patch is correctly placed on the body and paired with the mobile device) detected as part of onboarding on the Proteus device (during the Proteus Onboarding Visit). In the Investigator's opinion inadequate medication adherence is a potential factor in the subject's uncontrolled hypertension or diabetes. Exclusion Criteria: BMI > 40 kg/m2 as subjects may be more likely to have secondary reasons for out of control blood pressure (BP) and/or diabetes. History of skin sensitivity to adhesive medical tape or metals for subjects in the Intervention Arms. History of acute or chronic dermatitis for subjects in the Intervention Arms. Any condition that in the investigator's opinion could preclude safe participation in the study. Secondary cause for hypertension (eg, renal impairment or renal artery stenosis) or uncontrolled diabetes (eg, corticosteroid use). Mean SBP ≥ 180 mm Hg and/or DBP ≥ 110 mm Hg, if associated with evidence of hypertensive emergency.. Current or recent (within past year) treatment with insulin or other injectables for diabetes.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DH-4<br>Subjects will use Proteus Discover, the digital health offering (DH) for 4 weeks | Other: Proteus Discover<br>* FDA cleared Wearable Sensor with Ingestible Sensor and Mobile Device Application<br>|
| Active Comparator: DH-12<br>Subjects will use Proteus Discover, the digital health offering (DH) for 12 weeks | Other: Proteus Discover<br>* FDA cleared Wearable Sensor with Ingestible Sensor and Mobile Device Application<br>|
| Other: Usual Care<br>Subjects received usual medical care including all normal interventions such as medication titration, adherence counseling, lifestyle coaching, and additional clinic visits per their providers' discretion. | Other: Usual Care<br>* Routine medical care including medication titration, adherence counseling, and lifestyle coaching.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Week 4 Change in Systolic Blood Pressure |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Diastolic Blood Pressure |  | 4 weeks | 
| Proportion at blood pressure goal | BP < 140/90 mmHg | 4 weeks | 
| Proportion at blood pressure goal | BP < 140/90 mmHg | 12 weeks | 
| Change in Systolic Blood Pressure |  | 12 weeks | 
| Change in Diastolic Blood Pressure |  | 12 weeks | 
| Change in fasting plasma glucose |  | 4 weeks | 
| Change in fasting plasma glucose |  | 12 weeks | 
| Change in glycated hemoglobin |  | 12 weeks | 
| Average Daily Medication Adherence as Measured by DH | Medication adherence by medication and overall (aggregate average of daily adherence to each of the medications) in all DH subjects. Reported as a %. | 4 weeks | 
| Average Daily Medication Adherence as Measured by DH | Medication adherence by medication and overall (aggregate average of daily adherence to each of the medications) DH-12 subjects. Reported as a %. | 4 to 12 weeks | 
| Average daily physical activity duration as measured by DH in DH-12 subjects |  | 4 to 12 weeks | 
| Average daily rest duration as measured by DH in DH-12 subjects |  | 4 to 12 weeks | 
| Average daily step count as measured by DH in DH-12 subjects |  | 4 to 12 weeks | 
| Average daily step count as measured by DH in all DH subjects |  | 4 weeks | 
| Average daily physical activity duration as measured by DH in all DH subjects |  | 4 weeks | 
| Average daily rest duration as measured by DH in all DH subjects |  | 4 weeks | 
| Table Summary of the Number of Subjects with Medication Changes | Summary table of the number of medication dose increases, medication dose decreases, medication stops, medication additions, and no change. Data was summarized separately for hypertension, type 2 diabetes, and hypercholesterolemia. Data to be collected on CRF. Data summarized by type of medication change. | 4 weeks | 
| Table Summary of the Number of Subjects with Medication Changes | Summary table of the number of medication dose increases, medication dose decreases, medication stops, medication additions, and no change. Data was summarized separately for hypertension, type 2 diabetes, and hypercholesterolemia. Data to be collected on CRF. Data summarized by type of medication change. | 12 weeks | 
| Table Summary of the Number of Subjects with Medical Decisions Other than Medication Changes | Number of subjects who received adherence counseling, patient education, referral to a specialist, referral to disease management, lifestyle changes, and other medical decisions. Data summarized by type of decision. | 2 weeks | 
| Table Summary of the Number of Subjects with Medical Decisions Other than Medication Changes | Number of subjects who received adherence counseling, patient education, referral to a specialist, referral to disease management, lifestyle changes, and other medical decisions. Data summarized by type of decision. | 4 weeks | 
| Table Summary of the Number of Subjects with Medical Decisions Other than Medication Changes | Number of subjects who received adherence counseling, patient education, referral to a specialist, referral to disease management, lifestyle changes, and other medical decisions. Data summarized by type of decision. | 12 weeks | 
| Number of Treatment-Related Adverse Events | Descriptive summary of adverse events for DH arms versus usual care | 12 weeks |