Electrical Vestibular Nerve Stimulation (VeNS) Compared to Sham Control as a Means of Improving Glycemic Control in Adults With Type 2 Diabetes Mellitus

A Randomized, Double Blind Sham Controlled Clinical Trial to Evaluate the Efficacy of Vestibular Nerve Stimulation (VeNS), Together With a Lifestyle Modification Program, Compared to a Sham Control With a Lifestyle Modification Program, as a Means of Improving Glycemic Control in Adults With Type 2 Diabetes Mellitus

Trial Title A randomized, double blind sham controlled clinical trial to evaluate the efficacy of vestibular nerve stimulation (VeNS), together with a lifestyle modification program, compared to a sham control with a lifestyle modification program, as a means of improving glycemic control in adults with type 2 diabetes mellitus.

The aim of this study is to evaluate the efficacy of non-invasive electrical vestibular nerve stimulation (VeNS), together with a lifestyle modification program, as a method of reducing HbA1c, as compared to a sham control.

Allocation: Randomized to either active device or control device usage. All subjects will receive the same lifestyle advice.

Endpoint classification: Efficacy Study Intervention Model: Parallel Assignment in 1:1 active to control allocation Trial Participants: Those who have been diagnosed with Type 2 diabetes mellitus.

Sample Size: The aim is to recruit a total of 200 participants. Planned Trial Period: The study will last 24 weeks in total for each subject. The primary analysis will be conducted at the 24 weeks timepoint. The study in total is estimated to take about 1.5 years to complete.

Study Overview

• Status: Active, not recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Device: Vestal DM Active device; Behavioral: Lifestyle modification; Device: Vestal DM Sham device

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joshua Holmes; Phone Number: +44 2890991835; Email: joshua.holmes@neurovalens.com
• Study Contact Backup: Name: Joe Reel; Phone Number: +44 2890991835; Email: trials@neurovalens.com

Study Locations

• Ireland
  • Dublin 4
    • Dublin, Dublin 4, Ireland, D04 T6F4
      • St. Vincent's University Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego, Exercise and Physical Activity Resource Center
    • Sacramento, California, United States, 95821
      • Northern California Research
  • Florida
    • Hollywood, Florida, United States, 33020
      • New Med Research
    • Medley, Florida, United States, 33166
      • South Florida Research Organization
    • Mount Dora, Florida, United States, 32757
      • Adult Medicine of Lake County
    • Oviedo, Florida, United States, 32765
      • Oviedo Medical Research
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed Practices & Research
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Complete Health Partners
  • Texas
    • McAllen, Texas, United States, 78503
      • Biopharma Informatic
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
• Male or female, age ≥ 22 years and ≤ 70 years at the time of signing informed consent. (At the US sites). The non-US sites will recruit subjects aged ≥ 18 and ≤ 70 years.
• Diagnosed with Type 2 DM ≥ 90 days prior to day of enrolment
• HbA1c (glycated hemoglobin) ≥ 6.5 and ≤ 9.5% (48-80 mmol/mol) (both inclusive).
• If taking medication to treat diabetes, a stable dose of no more than 3 anti-diabetic medications for at least 90 days prior to enrolment.
• BMI ≥ 25 at non-US sites
• Must be under care of physician for follow-up of their type 2 DM (this can be a Primary Care Physician (PCP), endocrinologist or other hospitalist).
• Must agree to continue to participate with their routine diabetes care program.
• Access to Wi-Fi.

Exclusion Criteria:

• Diagnosis of Type 1 diabetes mellitus
• Diagnosis of diabetic neuropathy
• Diagnosis of diabetic nephropathy
• Diagnosis of retinopathy
• Skin breakdown, eczema or other dermatological condition (e.g. psoriasis) affecting the skin behind the ears. Any disorder which in the investigator's opinion might jeopardize subject's safety or compliance with the protocol.
• Taking beta-blockers (if previously then can enroll if off ≥ 30 days).
• Taking insulin (if previously on insulin then should be off for ≥ 90 days prior to enrolment).
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice)
• History of pancreatitis
• History of pancreatic surgery
• Hemochromatosis
• Either of the following within the previous year: myocardial infarction; or acute coronary syndrome.
• History of stroke
• History of epilepsy
• Splenectomy (due to effect on red blood cell turnover)
• History of anemia (if resolved for > 90 days with treatment then can enroll)
• Blood transfusion within 90 days of enrolment (due to effect on HbA1c). (If transfusion occurs once enrolled then subject will be withdrawn).
• A diagnosis of a hemoglobinopathy (e.g. sickle cell disease and thalassemia, although those with sickle cell or thalassemic trait would be allowed to enroll);
• If on dietary supplements or herbal remedies, then if the subject is taking a preparation that might affect glycemic control they will be excluded. Specifically, subject will be excluded if taking biotin (vitamin B7); alpha-lipoic acid; chromium; herbal preparations marketed as being for diabetes.
• History of being diagnosed with renal, heart or liver failure
• History of active migraines with aura
• History of head injury requiring intensive care or neurosurgery.
• Change in diabetic medication within the last 90 days (prior to enrolment).
• Regular use (more than twice a month) of antihistamine medication within the last 6 months. Note: If the participant is taking Fexofenadine, they can be eligible for the trial. If the participant is on another anti-histamine medication they can voluntarily opt to switch to Fexofenadine and enrol in the trial after a washout period of 2 weeks.
• Current use of H2-receptior antagonist medication? (e.g., cimetidine, famotidine)
• History or presence of malignancy within the last year (except basal and squamous cell skin cancer and in-situ carcinomas)
• A diagnosis of myelofibrosis or a myelodysplastic syndrome.
• Previous use of Modius device
• Participation in other clinical trials sponsored by Neurovalens (e.g. Vestal study)
• Presence of permanently implanted battery powered medical device or stimulator (e.g., pacemaker, implanted defibrillator, deep brain stimulator, vagal nerve stimulator etc.)
• Have a member of the same household who is currently participating in this study.
• History of vestibular dysfunction or other inner ear disease (as assessed on the screening questionnaire)
• Failure to pass the ATMAS Flex hearing test
• Failure to demonstrate a willingness for lifestyle modification (i.e diet and exercise) if BMI is ≥25 (as assessed on the screening questionnaire)
• Failure to agree to weekly engagements with the Clinical Trial Mentors during trial participation
• Failure to agree to use of device daily during trial participation (no more than 2 weeks usage drop without reasonable explanation)
• Use of any medication (e.g. hormonal modulators or corticosteroids) that could cause iatrogenic T2DM. (NB Topical steroid use is acceptable if judged by PI to be unrelated).
• Any other medical condition, or medication use, that in the opinion of the PI/CI is likely to make the subject refractory to VeNS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vestal DM active device; 150 subjects randomised to receive active device plus lifestyle intervention for 24 weeks	Device: Vestal DM Active device; Battery powered non-invasive neurostimulation device; Behavioral: Lifestyle modification; Subjects are prescribed a low calorie (500kcal deficit) diet if their BMI is ≥25. If a subject has a BMI of ≤24.9, they will be provided with guidance on ensuring their recommended daily dietary intake is achieved throughout the course of the trial (i.e 2,500kcal/day for men and 2,000kcal/day for women)
Sham Comparator: Vestal DM sham device; 150 subjects randomised to receive sham device plus lifestyle intervention for 24 weeks.	Behavioral: Lifestyle modification; Subjects are prescribed a low calorie (500kcal deficit) diet if their BMI is ≥25. If a subject has a BMI of ≤24.9, they will be provided with guidance on ensuring their recommended daily dietary intake is achieved throughout the course of the trial (i.e 2,500kcal/day for men and 2,000kcal/day for women); Device: Vestal DM Sham device; Placebo comparator sham device (no active stimulation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glycated hemoglobin (HbA1c)	Change in HbA1c levels over the course of the study	24 weeks
Frequency of all device related Serious Adverse Events	Frequency of all Device Related Serious Adverse Events (SAEs).	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants who achieve HbA1c targets	Participants Who Achieve HbA1c < 7.0 % (53 mmol/Mol) ADA Target (Yes/no),; Participants Who Achieve ≥ 0.5% HbA1c reduction (Performance goal of ≥ 50% of active group to be specified in SAP); Participants Who Achieve HbA1c ≤ 6.5 % (48 mmol/Mol) AACE Target (Yes/no)	24 weeks
Change in Body weight	Change in body weight as a percentage	24 weeks
Reduction of HbA1c in relation to weight loss	Assessment of reduction in HbA1c (%) per kg weight lost.	24 weeks
Change in BMI	Change in BMI across the duration of the study	24 weeks
Change in waist-hip ratio (WHR)	Change in waist-hip ratio (WHR) over time	24 weeks
Change in body composition (DXA scan)	Change in body composition (body fat percentage; body fat mass; visceral fat; muscle mass; bone mass) measured via a DXA scan	24 weeks
Change in atherogenic index	Change in the atherogenic index (ratio of total cholesterol to High Density Lipoprotein (HDL)	24 weeks
Change in pulse rate	change in pulse rate over time	24 weeks
Change in Mean arterial pressure (MAP)	Change in Mean arterial pressure (MAP). (MAP is approximately equal to (2/3 x DBP) + (1/3 x SP))	24 weeks
Change in fasting plasma glucose	Change in fasting plasma glucose	24 weeks
Change in 7 point Self Measured Blood Glucose (SMBG)	Change in 7 point SMBG - Ratio to Baseline	24 weeks
Change in anti-diabetic medication	Change in anti-diabetic medication. Diabetic medications will be summarized in terms of an increase, decrease or no change in medication, by treatment group. This assessment will be made by suitably qualified members of the study team.	24 weeks
Change in cardiovascular medication	Change in cardiovascular medication. The changes in cardiovascular medications will be summarized in terms of an increase, decrease or no change in cardiovascular medication, by treatment group. This assessment will be made by suitably qualified members of the study team.	24 weeks
Change in audit of diabetes dependent Quality of Life (QoL) score	Change in Audit of Diabetes Dependent Quality of Life Total Score (ADDQoL)	24 weeks
Tolerability of treatment	Tolerability of treatment summarized by: Duration of Exposure Device usage data Mentor support group usage (hours per week)	24 weeks
Frequency of Adverse Events (AEs)	Frequency of Adverse Events (AEs) (including Serious Adverse Events (SAEs)).	24 weeks
Frequency of hypoglycemic episodes	Change from baseline	24 Weeks

Collaborators and Investigators

• Sponsor: Neurovalens Ltd.
• Collaborators: University College Dublin; Clinical Trial Mentors; CS Lifescience
• Investigators: Principal Investigator: Erik Viirre, MD PhD, UC San Diego

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: VeSTALDM01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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