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Acute Study of Effect of Ultrasound Vagus Nerve Stimulation on Glycemia

Primary Purpose

Diabetes Mellitus, Type 2

Status

Suspended

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Ultrasound Vagus Nerve Stimulation (DECIMA)

About this trial

This is an interventional device feasibility trial for Diabetes Mellitus, Type 2

Eligibility Criteria

21 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent prior to any of the screening procedures
Willingness to comply with all study procedures and available for the duration of the study
Male or female age between 21 and 60 years old, inclusive
Diabetes Mellitus Type 2 for at least 1 year

Exclusion Criteria:

HbA1c greater than 10.5%
Medical treatment regimen with insulin
Medical treatment with antiinflammatory drugs such as Disease-Modifying Antirheumatic Drugs (DMARDs), i.e. Methotrexate and Cytokine-inhibitors, e.g. Adalimumab, and Etanercept.
Clinically significant neuropathy in the opinion of the investigator or as documented in the subject's medical history
Abundant fat tissue in neck, as evidenced by a neck circumference of more than 20''
Clinically significant surgical procedure(s) or skin lesion(s) in neck that would affect subject safety or placement of device
Prior vagotomy
History of clinically significant vasovagal syncope or presyncope
Use of electrically active implanted medical device
History of heat stroke or any heat intolerance that is deemed clinically significant in the opinion of the investigator
History of renal dysfunction or a glomerulonephropathy defined as either nephritic or nephrotic syndrome, including estimated glomerular filtration rate of <30 mL/min
Clinically significant cardiovascular condition or problem that in the opinion of the investigator would interfere with the study data or affect patient safety (e.g. uncontrolled hypertension, congestive heart failure, or documented evidence of prior coronary artery disease).
Pregnancy or plans to become pregnant while participating in the study, as determined by urine pregnancy test conducted at the screening visit for women of childbearing potential. A woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant. This includes women on oral, injectable, or mechanical contraception; women who are single; women whose husbands have been vasectomized or whose husbands have received or are utilizing mechanical contraceptive devices.
Uncontrolled asthma or obstructive lung disease.
History of sepsis
Significant cardiac rhythm disturbances in the opinion of the investigator based on an ECG.
GI surgery that could have lacerated any branch of the vagus nerve, i.e. cholecystectomy, gastrectomy, pancreatic surgery, etc.
Other conditions that could impair the patient's ability to participate in the study according to the investigator's opinion.

Sites / Locations

Cognitive Clinical Trials, LLC

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Active Comparator

Arm Label

Sham vs Active Stimulation Positions

Active uVNS

Arm Description

Adults with Diabetes Mellitus Type 2 (DMT2) will be recruited and randomized to active uVNS or sham across two sessions according to a 2x2 crossover design. Sham uVNS will be delivered with the same stimulation parameters as active uVNS, but will be targeted to the left sternocleidomastoid muscle ~2 cm away from the vagus nerve.

Active stimulations will be targeted with the ultrasound beam of the DECIMA device .Active uVNS will be delivered to the left cervical vagus nerve following the OGTT through the 60-min time point.

Outcomes

Primary Outcome Measures

Change in blood glucose Area Under the Curve (AUC, mg/dL ● hours) from baseline to 3 hours after an Oral Glucose Tolerance Test (OGTT) with Ultrasonic Vagus Nervous Stimulation (uVNS).hyperglycemia

The DECIMA device comprises an array of two focused ultra-sound applicators arranged with overlapping foci to deliver acoustic energy to a known focal depth within tissue.

Secondary Outcome Measures

Change in whole blood lipospolysaccharide-induced TNF-Alpha (pg/mL) production from base line to 4 hours post stimulation.

Inhibits postprandial hyperglycemia in patients with Diabetes Mellitus Type 2 via a temperature-medicated mechanism.

Full Information

NCT ID

NCT04094649

First Posted

August 6, 2019

Last Updated

August 16, 2021

Sponsor

Aucta Technologies, Inc.

Collaborators

STATKING Clinical Services

1. Study Identification

Unique Protocol Identification Number

NCT04094649

Brief Title

Acute Study of Effect of Ultrasound Vagus Nerve Stimulation on Glycemia

Official Title

This is a Single-site, Double-blind, Randomized, Prospective, Sham-controlled, Crossover Early Feasibility Study to Determine Whether Ultrasound Vagus Nerve Stimulation (uVNS) Inhibits Postprandial Hyperglycemia in Humans

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Suspended

Why Stopped

Pending funding

Study Start Date

August 1, 2019 (Actual)

Primary Completion Date

July 2022 (Anticipated)

Study Completion Date

July 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Aucta Technologies, Inc.

Collaborators

STATKING Clinical Services

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

This is an early feasibility study to evaluate the proof of concept of modulation of glycemia by non-invasive ultrasound vagus nerve stimulation. This protocol is exploratory in nature, therefore it is not intended to capture statistically valid results or test statistical hypotheses. However, statistical analysis of the primary endpoint will be performed to allow more critical reflection of the data and to estimate the treatment effect for consider-ation in further studies.

Detailed Description

The DECIMA device comprises an array of two focused ultra-sound applicators arranged with overlapping foci to deliver acoustic energy to a known focal depth within tissue. The focused ultrasound applicators are each comprised of an ultra-sound-emitting piezoelectric element coupled to a focusing lens. The array of the DECIMA device is coupled with an ultra-sound imaging system to locate the cervical vagus nerve, and a control system to deliver short bursts of ultrasound energy that are controlled by the operator in time and intensity. The imaging system and the array of applicators are calibrated together, so the power is focused at a known location relative to the imaging system screen. Each focused applicator's lens is joined to an ultrasound coupling cylinder filled with water. Each coupling cylinder is lined with thin plastic film at the skin. The ultrasound output power of the applicators is monitored by each applicator's control unit which includes a display of the ultrasound intensity. To perform ultrasound stimulation, ultrasound gel is placed on the skin over the nerve area in the neck. Then the coupling cylinders and imaging transducer are placed against the gel, then the DECIMA position is fixed in place by a support arm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose

Device Feasibility

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

This is a single-site, double-blind, randomized, prospective, sham-controlled, crossover early feasibility study to determine whether uVNS inhibits postprandial hyperglycemia in humans. Adults with DMT2 will be recruited and randomized to active uVNS or sham uVNS across two sessions according to a 2x2 crossover design.

Masking

ParticipantInvestigator

Masking Description

Randomization will be assigned by the clinical research facility. One of the two experimenters will be blinded. The unblinded experimenter is needed to aim the stimulation to the vagus nerve or sham location. The blinded experimenter will acquire, process, and analyze all data. Participants will be told that they may or may not feel the stimulation. The uVNS probe will be placed on their neck for each stimulation burst with the unblinded experimenter control-ling whether active or sham uVNS is delivered as determined by the crossover assignment.

Allocation

Randomized

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sham vs Active Stimulation Positions

Arm Type

Sham Comparator

Arm Description

Arm Title

Active uVNS

Arm Type

Active Comparator

Arm Description

Active stimulations will be targeted with the ultrasound beam of the DECIMA device .Active uVNS will be delivered to the left cervical vagus nerve following the OGTT through the 60-min time point.

Intervention Type

Device

Intervention Name(s)

Ultrasound Vagus Nerve Stimulation (DECIMA)

Intervention Description

This is a single-site, double-blind, randomized, prospective, sham-controlled, crossover early feasibility study to determine whether ultrasound Vagus Nerve Stimulation (uVNS) inhibits postprandial hyperglycemia in humans.

Primary Outcome Measure Information:

Title

Change in blood glucose Area Under the Curve (AUC, mg/dL ● hours) from baseline to 3 hours after an Oral Glucose Tolerance Test (OGTT) with Ultrasonic Vagus Nervous Stimulation (uVNS).hyperglycemia

Description

The DECIMA device comprises an array of two focused ultra-sound applicators arranged with overlapping foci to deliver acoustic energy to a known focal depth within tissue.

Time Frame

Change from baseline in the 3-hour mean glucose AUC following an OGTT

Secondary Outcome Measure Information:

Title

Change in whole blood lipospolysaccharide-induced TNF-Alpha (pg/mL) production from base line to 4 hours post stimulation.

Description

Inhibits postprandial hyperglycemia in patients with Diabetes Mellitus Type 2 via a temperature-medicated mechanism.

Time Frame

Change in mean Whole Blood Lipopolysaccharide-Induced TNF production from baseline to four (4) hours post-stimulation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent prior to any of the screening procedures Willingness to comply with all study procedures and available for the duration of the study Male or female age between 21 and 60 years old, inclusive Diabetes Mellitus Type 2 for at least 1 year Exclusion Criteria: HbA1c greater than 10.5% Medical treatment regimen with insulin Medical treatment with antiinflammatory drugs such as Disease-Modifying Antirheumatic Drugs (DMARDs), i.e. Methotrexate and Cytokine-inhibitors, e.g. Adalimumab, and Etanercept. Clinically significant neuropathy in the opinion of the investigator or as documented in the subject's medical history Abundant fat tissue in neck, as evidenced by a neck circumference of more than 20'' Clinically significant surgical procedure(s) or skin lesion(s) in neck that would affect subject safety or placement of device Prior vagotomy History of clinically significant vasovagal syncope or presyncope Use of electrically active implanted medical device History of heat stroke or any heat intolerance that is deemed clinically significant in the opinion of the investigator History of renal dysfunction or a glomerulonephropathy defined as either nephritic or nephrotic syndrome, including estimated glomerular filtration rate of <30 mL/min Clinically significant cardiovascular condition or problem that in the opinion of the investigator would interfere with the study data or affect patient safety (e.g. uncontrolled hypertension, congestive heart failure, or documented evidence of prior coronary artery disease). Pregnancy or plans to become pregnant while participating in the study, as determined by urine pregnancy test conducted at the screening visit for women of childbearing potential. A woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant. This includes women on oral, injectable, or mechanical contraception; women who are single; women whose husbands have been vasectomized or whose husbands have received or are utilizing mechanical contraceptive devices. Uncontrolled asthma or obstructive lung disease. History of sepsis Significant cardiac rhythm disturbances in the opinion of the investigator based on an ECG. GI surgery that could have lacerated any branch of the vagus nerve, i.e. cholecystectomy, gastrectomy, pancreatic surgery, etc. Other conditions that could impair the patient's ability to participate in the study according to the investigator's opinion.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Albert Tejada, MD, PI

Organizational Affiliation

Synexus

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cognitive Clinical Trials, LLC

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85258

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Acute Study of Effect of Ultrasound Vagus Nerve Stimulation on Glycemia

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