## Protocol Section
### Identification Module
**NCT ID:** NCT04467879

**Brief Title:** A Pivotal Study To Evaluate The Effectiveness of Isometric Handgrip Therapy In Prehypertensive And Hypertensive Patients

**Official Title:** A Pivotal Study To Evaluate The Effectiveness of Isometric Handgrip Therapy In Prehypertensive And Hypertensive Patients

#### Organization Study ID Info
**ID:** 001
#### Organization
**Class:** INDUSTRY
**Full Name:** Zona Health, Inc
### Status Module
#### Completion Date
**Date:** 2022-09-14

**Type:** ACTUAL

#### Last Update Post Date
**Date:** 2022-09-22

**Type:** ACTUAL

**Last Update Submit Date:** 2022-09-19

**Overall Status:** TERMINATED

#### Primary Completion Date
**Date:** 2022-09-13

**Type:** ACTUAL

#### Start Date
**Date:** 2020-06-01

**Type:** ACTUAL

**Status Verified Date:** 2022-09

#### Study First Post Date
**Date:** 2020-07-13
**Type:** ACTUAL
**Study First Submit Date:** 2020-07-08
**Study First Submit QC Date:** 2020-07-08
**Why Stopped:** New Protocol and Outcome Measures in Review
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** Research & Development Concierge Company

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Zona Health, Inc

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Is Unapproved Device:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This is a double-blind, sham-controlled clinical trial assessing the effectiveness of personalized isometric handgrip device therapy. Approximately 230 patients who present with a Systolic Blood Pressure reading of ≤ 149mmHg and who have not taken any antihypertensive medication for more than 30 days will be enrolled.

**Detailed Description:** This study is designed to examine the effectiveness of individualized isometric handgrip device therapy in prehypertension or hypertension patient subjects who are not at target BP and who are naive to anti-hypertensive medication for at least 30 days before screening. The investigational plan examines changes in blood pressure (BP) in up to 230 patient subjects who are randomized to either the "active" (i.e., the Zona Plus device proposed for marketing), or to a "sham" device (which is intentionally calibrated for a "weaker grip").

### Conditions Module

**Conditions:**

- Hypertension, Systolic

**Keywords:**

- Diastolic Hypertension

- HandGrip Therapy

- Pre-Hypertension

- Isometric Exercise

- Vascular Hypertension

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Prospective, double-blinded, randomized, sham-controlled study

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** Double Blinded

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 146

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Using the Zona Plus Device, the patient will perform a twelve-minute isometric handgrip therapy session at approximately the same time each day . After an initial handgrip strength assessment (the session calibration), a two-minute isometric routine is performed four times, two sessions per hand, with a one-minute non-grip, or rest session between each isometric routine.

**Intervention Names:**

- Device: Zona Plus Device

**Label:** Zona Plus - Active - "Normal Grip"

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Using the Zona Sham Control Device the patient will perform a twelve-minute isometric handgrip therapy session at approximately the same time each day. After an initial handgrip strength assessment (the calibration), a two-minute isometric routine is performed four times, two sessions per hand, with a one-minute non-grip, or rest session between each isometric routine.

**Intervention Names:**

- Device: Control Device

**Label:** Control Device - Sham - "Weaker Grip"

**Type:** SHAM_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Zona Plus - Active - "Normal Grip"

**Description:** Zona Plus 3.0 Individualized Isometric Handgrip Therapy Device

**Name:** Zona Plus Device

**Other Names:**

- Zona Plus 3.0

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- Control Device - Sham - "Weaker Grip"

**Description:** Zona Plus control sham device, with a nominal weaker grip

**Name:** Control Device

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Comparative assessment in the change from Baseline in seated cuff Systolic Blood Pressure after ten(10) weeks of treatment between patients treated with the Zona Plus nominal device ("stronger grip") and patients treated with the Placebo control device ("weaker grip"). A reduction in Systolic Blood ≥ 5 Preassure after 10 weeks of treatment is considered to be a better outcome.

**Measure:** Change from Baseline in Systolic Blood Pressure to Day 70 ± 2 Days

**Time Frame:** Change from Baseline to Day 70 ±2 Days

#### Secondary Outcomes

**Description:** Comparative assessment of the change from Baseline in seated cuff Diastolic Blood Pressure after 10 weeks of treatment between patients treated with the Zona Plus nominal device ("stronger grip") and patients treated with the Placebo control device ("weaker grip").

**Measure:** Change from Baseline in Diastolic Blood Pressure to Day 70 ± 2 Days

**Time Frame:** Change from Baseline to Day 70 ±2 Days

**Description:** Comparative assessment in the percentage of patients who achieve a clinically significant Systolic Blood Pressure reduction (defined as ≥ 5 mmHg) at Day 70 ± 2 Days.

**Measure:** Percentage change from Baseline in Systolic Blood Pressure reduction at Day 70 ± 2 Days

**Time Frame:** Change from Baseline to Day 70 ± 2 Days

**Description:** Comparative assessment in the percentage of patients who achieve a clinically significant Diastolic Blood Pressure reduction (defined as ≥3 mmHg) at Day 70 ± 2 Days.

**Measure:** Percentage change from Baseline in Diastolic Blood Pressure reduction at Day 70 ± 2 Days

**Time Frame:** Change from Baseline to Day 70 ± 2 Days

**Description:** Comparative assessment in change from Baseline in the seated cuff Systolic Blood Pressure after 6 months Day 160 ± 4 of treatment between patients treated with the Zona Plus nominal device and patients treated with the Placebo control device.

**Measure:** Percentage change from Baseline in Systolic Blood Pressure reduction at Day 160 ± 4 Days

**Time Frame:** Change from Baseline to Day 160 ± 4 Days

**Description:** Comparative assessment in change from Baseline in the seated cuff Diastolic Blood Pressure after 6 months Day 160 ± 4 Days of treatment between patients treated with the Zona Plus nominal device and patients treated with the Placebo control device.

**Measure:** Percentage change in Diastolic Blood Pressure reduction at Day 160 ± 4 Days

**Time Frame:** Change from Baseline to Day 160 ± 4 Days

**Description:** Comparative assessment in the percentage of patients who achieve a clinically significant Systolic Blood Pressure reduction (defined as ≥ 5 mmHg) at Day 160 ± 4 Days

**Measure:** Percentage change from Baseline in Systolic Blood Pressure reduction at Day 160 ± 4 Days

**Time Frame:** Change from Baseline to Day 160 ± 4 Days

**Description:** Comparative assessment in the percentage of patients who achieve a clinically significant Diastolic Blood Pressure reduction defined as ≥3 mmHg at Day 160 ± 4 Days

**Measure:** Percentage change in Diastolic Blood Pressure reduction at Day 160 ± 4 Days

**Time Frame:** Change from Baseline to Day 160 ± 4 Days

**Description:** The Heart Rate (HR) will be recorded and compared between the Zona Plus nominal device and the Placebo control device treatment groups.

**Measure:** Comparison of Heart Rate between Zona Plus nominal device and Placebo controlled device

**Time Frame:** Change from Baseline to Day 160 ± 4 Days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria

* Male or female of any ethnicity between 18 and 80 years of age
* Diagnosed with prehypertension or hypertension and verified during the Baseline visit
* Non-use of antihypertensive medication for ≥30 prior to screening
* Currently not taking any antihypertensive medications or decline to take any antihypertensive medications(e.g., diuretic, angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), \] beta-blocker (BB), renin inhibitor (RI), calcium channel blocker (CCB) or alpha-adrenergic agonist (clonidine))
* Sufficient vision with the patient able to see the screen prompts on the device, sufficient hearing with the patient able to hear the device audio prompts, sufficient hand strength (demonstrated by a maximum voluntary contraction equaling 35 units of force in both hands measured by the device)
* Baseline Blood Pressure measurements collected and study device training completed during the Baseline visit
* Non-use of medications and over the counter (OTC)supplement regimen related to hypertension throughout the study duration
* Only one patient per household can participate in the study, eliminating the potential of unblinding
* Able to comply with study procedures and agrees to complete all required study visits and associated activities
* Ability to give written informed consent in either English, Spanish or French •≤149 mmHg, Systolic Blood Pressure wherein patients who present with Systolic Blood Pressure readings ≥140 mmHg will receive heightened monitoring throughout the first month of the study

Exclusion Criteria

* Pregnant or not using adequate contraception
* Blood Pressure ≥150 mmHg (systolic) and/or \>90 mmHg (diastolic)
* History of heart failure
* Hospitalization due to a hypertensive emergency, with impending or progressive target organ dysfunction (i.e., renal dysfunction, left ventricular hypertrophy or CNS involvement) within the past six (6) months

  •\>10 mmHg difference in Systolic Blood Pressure between the right and left arms collected during screening
* Unstable Blood Pressure, defined as \>5 mmHg variance between any two (2) consecutive weekly readings (with a maximum of four (4) attempts) to determine a baseline BP measurement
* Arm circumference greater than 45cm
* Acute illness, infection, or inflammation
* Unstable cardiovascular disorder, such as MI, unstable angina, significant arrhythmia, stroke, or TIA within the last six (6)months, or other serious comorbidity impacting life expectancy to \< than a 1 year
* Rest or exertional angina pectoris in the previous six (6) months
* History of solid organ transplant
* Secondary form of hypertension (HTN) etiology, including but not limited to primary aldosteronism, chronic steroid therapy and Cushing syndrome, pheochromocytoma, aorta coarctation or untreated thyroid or parathyroid disease
* Concurrent participation in an investigational clinical study that has not completed the follow-up period or planned participation in another study within the next six(6) months
* Any condition or personal circumstance that, in the judgment of the investigator, might interfere with the collection of complete, good quality data or the completion of the research study
* Currently own or have owned another Zona Plus device and are,or have been,voluntarily performing the isometric handgrip activities.

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Saint Louis

**Country:** United States

**Facility:** Saint Louis Heart & Vascular, P.C.

**State:** Missouri

**Zip:** 63044

**Location 2:**

**City:** Charlotte

**Country:** United States

**Facility:** Carolinas Research Center LLC

**State:** North Carolina

**Zip:** 28215

**Location 3:**

**City:** Goldsboro

**Country:** United States

**Facility:** Goldsboro Medical Center

**State:** North Carolina

**Zip:** 27534

**Location 4:**

**City:** Kerrville

**Country:** United States

**Facility:** Sante Clinical Research

**State:** Texas

**Zip:** 78028

**Location 5:**

**City:** San Antonio

**Country:** United States

**Facility:** Sun Research Institute

**State:** Texas

**Zip:** 78215

#### Overall Officials

**Official 1:**

**Affiliation:** Zona Health, Inc

**Name:** Mark Young

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**Description:** If in the future Investigators want to access the data for secondary analysis they can submit a request from the Sponsor or R\&D Data Management Contact. Individual patient data will not be shared by the sponsor directly and will be aggregated, monitored, and de-identified (APD) via 1) final approved clinical study report 2) any manuscripts or summary results report via an email request to the central contact once database lock has occurred and reports are generated.

**IPD Sharing:** NO

### References Module

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**Citation:** Millar PJ, Paashuis A, McCartney. Isometric Handgrip Effects on Hypertension. CurrHypertens Rev 2009;5:54-60

#### See Also Links

**Label:** Drug Labeling for Cardiovascular Outcome Claims

**URL:** http://www.fda.gov/regulatory-information/search-fda-guidance-documents/hypertension-indication-drug-labeling-cardiovascular-outcome-claims

**Label:** Principles for ClinicalEvaluation ofNew Antihypertensive Drugs.

**URL:** http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073147.pdf

**Label:** The Seventh Report of the Joint National Committee on Prevention, Detection,Evaluation, and Treatment of High Blood Pressure

**URL:** http://www.nhlbi.nih.gov/files/docs/guidelines/jnc7full.pdf

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000075222

- Term: Essential Hypertension

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10024

- Name: Hypertension

- Relevance: HIGH

- As Found: Hypertension

- ID: M29007

- Name: Prehypertension

- Relevance: LOW

- As Found: Unknown

- ID: M27583

- Name: Systolic Murmurs

- Relevance: LOW

- As Found: Unknown

- ID: M2913

- Name: Isolated Systolic Hypertension

- Relevance: HIGH

- As Found: Hypertension, Systolic

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M1470

- Name: Essential Hypertension

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006973

- Term: Hypertension

- ID: D000092244

- Term: Isolated Systolic Hypertension

### Misc Info Module

- Version Holder: 2024-05-24
