The Baroloop Study

A First in Human Study of Feasibility of Baroloop: The Baroloop Study

The baroloop Study is a non-randomized, prospective, single-arm, multi center First in Human (FIH) study with the primary objective being the assessment of the safety and feasibility of using the baroloop System in subjects with uncontrollable hypertension. The secondary objective is to document the effect of the baroloop device on the blood pressure and quality of life in subjects with hypertension. Up to 10 subjects will be enrolled in up to 3 sites in Europe.

Study Overview

• Status: Terminated
• Conditions: Hypertension
• Intervention / Treatment: Device: baroloop System

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stephanie Schmitz-Weckauf; Phone Number: +497611543390; Email: study@neuroloop.de

Study Locations

• Netherlands
  • Utrecht, Netherlands
    • UMC Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 years or older and less than 80 years of age.
2. Persistent office systolic blood pressure (SBP) ≥ 140 mm Hg and diastolic blood pressure (DBP) > 90 mm Hg on antihypertensive medicines on two visits separated by a minimum of four weeks.
3. Mean 24-hour systolic ABPM ≥ 130 mm Hg and mean 24 hour diastolic ABPM ≥ 80 mm Hg conducted after direct observed therapy to confirm that antihypertensive medicines were taken as prescribed during the ABPM measurement.
4. Stable drug regimen of 4 antihypertensive medicines consisting of a renin-angiotensin blocker(ACE) or Angiotensin II Receptor Blocker (ARBs), a calcium channel blocker (CCB), a diuretic and spironolactone for 4 weeks at treatment. If spironolactone is not tolerated, the regimen must include instead the addition of further diuretic therapy with either eplerenone, amiloride, higher-dose thiazide/thiazide-like diuretic or a loop diuretic, or the addition of bisoprolol or doxazosin. If none of these medicines are tolerated, then patients on a 3-drug regimen may be included.
5. The Investigator has confirmed that the patient has already tried and/or is not suitable for treatment with currently CE-marked device-based therapies for resistant hypertension as an alternative to baroloop therapy.
6. Willingness and ability to comply with follow-up requirements.
7. Signed informed consent.

Exclusion Criteria:

1. Any patient in whom access to the vagal nerve is limited by the size of the vagus (a size not compatible with the baroloop cuff).
2. Any patient with a history of injury to the vagus nerve or its branches (e.g., the recurrent laryngeal nerve).
3. Secondary causes of hypertension.
4. Calculated eGFR < 30 mL/min/1.73m2.
5. Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1c > 10%).
6. One or more episodes of orthostatic hypotension in the past year
7. Requirement for chronic oxygen therapy or mechanical ventilation.
8. Untreated (no CPAP therapy) sleep apnea (AHI > 15)
9. Morbid obesity, defined as Body Mass Index >40 kg/m2 or arm circumference 46 cm.
10. Pacemaker and/or implantable defibrillators.
11. History of transient ischemic accident or cerebrovascular accident during six (6) months prior to screening.
12. Symptomatic carotid artery disease or > 70% occlusion of either carotid artery; any carotid malformation or lesion, a carotid bruit or other abnormal carotid sound.
13. Prior surgery, radiation therapy or scarring in the neck in the region of the carotid artery (e.g., patients with a tracheostomy, extensive thymectomy or thyroid surgery).
14. Limited mobility of the neck secondary to vertebral disease or prior vertebral surgery, including patients who wear a cervical support.
15. History of heart failure (NYHA class III-IV or ejection fraction < 30%), myocardial infarction, unstable angina, coronary bypass or coronary angioplasty during six (6) months prior to screening.
16. Cardiac arrythmias (atrial fibrillation, atrial flutter, etc.) that require anticoagulation or interfere with a consistent measurement of blood pressure.
17. Syncope in the last 6 months.
18. History of bleeding disorders, thrombocytopenia, hemophilia or significant anemia (hemoglobin (Hgb) < 10 gm/dl).
19. Current anticoagulation therapy (excluding antiplatelet therapy with aspirin as a sole therapy).
20. Works night shifts.
21. History of unresolved drug or alcohol use.
22. Active treatment of a psychiatric ailment.
23. Life expectancy of less than 12 months due to other disease.
24. Subject has a condition that, in the opinion of the investigator, precludes participation, including willingness to comply, with all follow-up procedures.
25. Participation in another clinical study for which follow-up is currently on-going.
26. Women who are of child-bearing age or who have the potential to become pregnant
27. Resting heart rate of <40 beats/min for patients on beta blockers or <60 beats/min for all other patients, confirmed at both baseline visits.
28. Baroreflex failure or autonomic neuropathy
29. Symptomatic, uncontrolled bradyarrhythmias
30. Atrioventricular block of any grade
31. Patients who are treated with Pacemaker and/or implantable defibrillators
32. Presence of a vagus stimulator
33. Patients who expect to require magnetic resonance imaging (MRI) of the cervical area
34. Occupational exposure to high levels of non-ionizing radiation that may interfere with therapy
35. Patients with a limited ability to read, understand and execute adjustment procedures (for example, persons suffering from dementia).
36. Likely exposure to diathermy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Device; Subjects implanted with the baroloop device	Device: baroloop System; vagal nerve stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Major Adverse Event (MAE) Rate	The MAE consists of all causes of death, hospitalization for hypertensive crisis post-titration, and any device or procedure-related serious adverse events	at 6 months post-treatment
Feasibility - device placement and vagal nerve stimulation	Feasibility is defined as the ability of the baroloop System to be placed around a vagal nerve and to stimulate the nerve	Day 14 or Day 21 post-implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood pressure	Change in blood pressure recorded during intraoperative stimulation	at the time of implantation
Change in 24-hour ABPM	Mean change of 24-hour ambulatory systolic and diastolic blood pressure post-treatment versus baseline	1, 3, 6, 12, 18 and 24 months
Composite MAE rate	he MAE consists of all causes of death, hospitalization for hypertensive crisis post-titration, and any device or procedure-related serious adverse events	1, 3, 12, 18 and 24 months
Change in Office Blood Pressure	Mean change in office systolic and diastolic blood pressure	1, 3, 6, 12, 18 and 24 months
Change in antihypertensive drugs/dosages	Changes in antihypertensive drugs/dosages post-implantation as analyzed by Daily Defined Dosages (WHO Definition) and total medications	1, 3, 6, 12, 18 and 24 months
Quality of Life Evaluation - Short Form (36) Health Survey	Quality of Life as measured by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	Baseline, 1, 3, 6, 12, 18 and 24 months

Collaborators and Investigators

• Sponsor: neuroloop GmbH
• Collaborators: MAXIS GmbH
• Investigators: Principal Investigator: Wilko Spiering, UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Actual): October 5, 2023
• Study Completion (Actual): October 5, 2023

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): July 29, 2021

Study Record Updates

• Last Update Posted (Actual): December 7, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: BL_CIP-FIH

Drug and device information, study documents

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