Proteus Discover in Subjects With Uncontrolled Hypertension and Type 2 Diabetes

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Diabetes Mellitus, Type 2; Hypercholesterolemia
• Intervention / Treatment: Other: Proteus Discover; Other: Usual Care

Detailed Description

"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.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. SBP is ≥ 140 mm Hg (and his/her BP goal is < 140/90 mm Hg).
  2. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DH-4; Subjects will use Proteus Discover, the digital health offering (DH) for 4 weeks	Other: Proteus Discover; FDA cleared Wearable Sensor with Ingestible Sensor and Mobile Device Application
Active Comparator: DH-12; Subjects will use Proteus Discover, the digital health offering (DH) for 12 weeks	Other: Proteus Discover; FDA cleared Wearable Sensor with Ingestible Sensor and Mobile Device Application
Other: Usual Care; 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; Routine medical care including medication titration, adherence counseling, and lifestyle coaching.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Systolic Blood Pressure		12 weeks
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 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LDL in subjects using a statin		4 weeks
Change in LDL in subjects using a statin		12 weeks
Change in ACC/AHA ASCVD 10-year risk		4 weeks
Change in ACC/AHA ASCVD 10-year risk	American College of Cardiology/ American Heart Association Atherosclerotic Cardiovascular Disease Risk Score	12 weeks
Change in Patient Activation Measure (PAM)	PAM is a validated measure of patient activation	4 weeks
Change in Patient Activation Measure (PAM)	PAM is a validated measure of patient activation	12 weeks
Resource Utilization: Summary of the number of outpatient visits, ER visits, and hospitalizations during the study	Data to be summarized descriptively	12 weeks
Proportion of subjects with adequate activity and rest information while using Proteus Discover		4 weeks
Proportion of subjects with adequate activity and rest information while using Proteus Discover		12 weeks
Change in weight in kg		4 weeks
Change in weight in kg		12 weeks
Change in BMI in kg/m^2		4 weeks
Change in BMI in kg/m^2		12 weeks
Change in waist circumference (cm)		4 weeks
Change in waist circumference (cm)		12 weeks
Subject Reported Outcomes: Results from a subject satisfaction [to DH] questionnaire administered at the end of using DH.	Satisfaction (with Proteus Discover) survey administered upon completion of use of Proteus Discover	4 or 12 weeks
Provider Reported Outcomes: Results from a provider satisfaction [to DH] questionnaire administered at the end of using DH.	Satisfaction (with Proteus Discover) survey administered upon completion of the study	4 or 12 weeks

Collaborators and Investigators

• Sponsor: Proteus Digital Health, Inc.
• Collaborators: Syneos Health
• Investigators: Principal Investigator: Lars Osterberg, MD, Stanford University

Publications and helpful links

General Publications

• Centers for Disease Control and Prevention (CDC). Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol--United States, 1999-2002 and 2005-200. MMWR Morb Mortal Wkly Rep. 2011 Feb 4;60(4):109-14.
• Frias J, Virdi N, Raja P, Kim Y, Savage G, Osterberg L. Effectiveness of Digital Medicines to Improve Clinical Outcomes in Patients with Uncontrolled Hypertension and Type 2 Diabetes: Prospective, Open-Label, Cluster-Randomized Pilot Clinical Trial. J Med Internet Res. 2017 Jul 11;19(7):e246. doi: 10.2196/jmir.7833.

Helpful Links

• American Diabetes Association. Statistics about diabetes.
• Centers for Disease Control and Prevention. National diabetes statistics report: estimates of diabetes and its burden in the United States, 2014.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: June 29, 2016
• First Submitted That Met QC Criteria: July 5, 2016
• First Posted (Estimate): July 11, 2016

Study Record Updates

• Last Update Posted (Estimate): July 11, 2016
• Last Update Submitted That Met QC Criteria: July 5, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypercholesterolemia
• Other Study ID Numbers: PB-DISC_CMB_01