Vestibular Stimulation to Trigger Adipose Loss (VeSTAL) Clinical Trial

Study Overview
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Brief Summary
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A randomized, double blind sham controlled clinical trial to evaluate the efficacy of vestibular nerve stimulation (VeNS), combined with a lifestyle modification program, compared to a sham control and a lifestyle modification program as a means of reducing excess body weight and body fat. The purpose of this investigation device study is to collect data to support regulatory submissions, primarily in the United States of America (USA), but it may also be used to support submissions in other regions, including the European Union (EU).

Detailed Description
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In total there will be approximately 200 patients enrolled on the study around both sites. At the UCSD site there will be a total of about 106 total subjects (53 active treatment and 53 control subjects) who are randomized into the treatment protocols having passed the screening criteria. At the UU site there will be a total of about 94 total subjects (47 active and 47 control subjects). 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 excess body weight and body fat, as compared to a sham control with both study arms incorporating a lifestyle modification program. Allocation: Randomized Endpoint classification: Efficacy Study Intervention Model: Parallel Assignment in 1:1 active to control allocation The aim of the study is to recruit a total (i.e. across both sites) of 200 participants that pass the screening process and are randomized into the treatment protocols. With a dropout allowance of 10% this should generate a minimum of 90 active treatment and 90 control subjects. (In order to achieve adequate numbers, Neurovalens Ltd. estimate that the clinical site may have to consent (i.e. enroll into the study) up to 150 subjects at the UCSD site, in order to achieve adequate numbers, it is estimated that the clinical site may have to consent (i.e. enroll into the study) up to 150 subjects at the UU site, as the baseline screening can only take place after the formal consent process as the baseline screening can only take place after the formal consent process.) The designation of treatment across the two study sites will be as follows: USCD: a total of about 106 subjects who pass through screening and are randomized (53 active treatment and 53 control subjects); University of Ulster: a total of about 94 total subjects who pass through screening and are randomized (47 active and 47 control subjects). Masking: Double Blind (Subject, Nursing staff, Dietician, Co-coordinators, Outcomes Assessor and any other study staff who have contact with the subject) Data from both sites will be collated at the end of the studies and analysis will be performed on one data set. Study staff will train the subject on how to use their study device. Specifically this will include: how to first prepare the skin over the mastoid processes with an alcohol wipe; a demonstration of where to place the hydrogel electrodes; how to access the VeSTAL study app and pair the iPod (using Bluetooth) to the device; how to operate the device using the app; and how to use the up/down buttons on the device if unable to use the study app. Study staff will provide subjects with a printed copy of the IFU and also highlight its location as a PDF on the iPod. The Device Use Schematic will also be highlighted to the subjects - it will only be as a PDF on the iPod. Also study staff will demonstrate to the subjects: how to charge the device; to dispose of used electrodes after a stimulation session; how to store unused electrodes in a sealed manner so they do not dry out; how to turn the device on and off using the power button; and how to use the app or power button to pause a stimulation session. Subjects will be asked to try and use their allocated device for an hour every day, and at least five times a week. Theoretically it is thought that the device may be more effective if used while sitting upright (as opposed to lying flat), due to the orientation of the otolith organs. As such subjects will be encouraged to use the device while sitting upright, and also in the evening as sometimes people can feel a bit soporific after vestibular stimulation. Subjects will be instructed not to walk around, operate machinery or drive while using their device.

Official Title
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Clinical Investigation Protocol for the Demonstration of Safety and Efficacy of VeSTAL Weight Loss Device in Human Subjects. Randomized Study of VeSTAL in Patients Who Are Overweight

Conditions
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Obesity

Intervention / Treatment
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* Device: VeSTAL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) ≥ 27 kg/m2 Males or Females. Note females of child-bearing potential must have a negative urine pregnancy test at screen and also just before each DXA scan. (As DXA involves a small dose of ionizing radiation). They should agree to follow a physician-approved contraceptive regimen for the duration of the study period (other than DMPA injections as this causes weight gain). 22-80 years of age inclusive on starting the study. (In order to comply with FDA guidance: https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm089740.htm#s6) Ability and willingness to complete all study visits and procedures; in particular an agreement to engage with: trying to use the device on a daily basis; the hypocaloric diet weight loss program; and this provided weight loss support and mentoring. Agreement not to use of prescription, or over-the-counter, weight loss preparations for the duration of the trial. Agreement not to start smoking or vaping tobacco for the duration of the study. Access to Wi-Fi (to connect iPod to internet) Exclusion Criteria: History of vestibular dysfunction. History of bariatric surgery, or gastric resection. History of skin breakdown, eczema or other dermatological condition (e.g. psoriasis) affecting the skin behind the ears. History of weight loss device implantation (e.g. VBloc Maestro or Abiliti). Use of a non-invasive weight loss device (e.g. Modius) Hypothyroidism requiring current treatment with levothyroxine (e.g. Levo-T, Synthroid, Thyroxine) (Other thyroid disorder patients on stable treatment for at least 3 months are acceptable). Other endocrinological causes of weight gain (e.g. Cushing's disease, Cushing's syndrome or acromegaly) Previous diagnosis of HIV infection or AIDS (HIV is known to cause a vestibular neuropathy which would prevent VeNS from working). Diagnosis of cirrhosis, chronic pancreatitis, or liver, kidney or heart failure. Treatment with prescription weight-loss drug therapy in the 6 months before starting the study. Tobacco smoking (including vaping) in the six months prior to starting and for the duration of the study. Use of marijuana (smoking, vaping or in edible form) more than twice a month on average. Known genetic cause of obesity (e.g., Prader-Willi Syndrome). Body weight change of more than 20% in either direction within the previous year. Physician-prescribed diet, and/ or current, active member of an organized weight loss program. Diabetes mellitus (Types 1 & 2). Diagnosis of epilepsy or use of anti-epileptic medication within six months of starting the study (e.g. for the treatment of peripheral neuropathy) Chronic (more than a month of daily use) treatment with opioid analgesic drugs within the last 6 months. Regular use (more than twice a month) of anti-histamine medication within the last 6 months. Use of oral or intravenous corticosteroid medication within 6 months of starting the study. Use of beta-blockers within 3 months of starting the study. Current alterations in treatment regimens of anti-depressant medication for whatever reason (including tricyclic antidepressants) (Note: stable treatment regimen for prior 6 months acceptable). An active diagnosis of cancer. A myocardial infarction within the preceding year. A history of stroke or severe head injury (as defined by a head injury that required craniotomy or endotracheal intubation). (In case this damaged the neurological pathways involved in vestibular stimulation). Presence of permanently implanted battery powered medical device or stimulator (e.g., pacemaker, implanted defibrillator, deep brain stimulator, vagal nerve stimulator etc.). Psychiatric disorders (including untreated severe depression, schizophrenia, substance abuse, eating disorder etc.) Current participant in another weight loss study or other clinical trial. Have a family member who is currently participating or is planning to participate in this study. Weight over 350 pounds at UCSD site or 202kg at the UU site, as these weights are the limits of the respective DXA scanners. Pregnancy

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VeSTAL - active device<br>The VeSTAL device utilizes a technology called galvanic vestibular stimulation (GVS) (sometimes termed vestibular nerve stimulation (VeNS)). The device will be placed on the head in a manner analogous to headphones and will deliver a small electrical current to the skin behind the ears, over the mastoid processes. Participants will be advised to use the device at home for 1 hour per day. | Device: VeSTAL<br>* The aim of this study is to evaluate the efficacy of non-invasive electrical vestibular nerve stimulation in combination with a lifestyle modification program, as a method of reducing excess body weight and body fat, as compared to a sham device in combination with the same lifestyle modification program.<br>|
| Sham Comparator: Sham device<br>The sham device looks identical to the active device and interacts with the app in a similar manner to the active device. However, it does not deliver vestibular stimulation to users. The device will be placed on the head in a manner analogous to headphones with hydrogel electrodes placed over the mastoid processes. Participants will be advised to use the device at home for 1 hour per day. | Device: VeSTAL<br>* The aim of this study is to evaluate the efficacy of non-invasive electrical vestibular nerve stimulation in combination with a lifestyle modification program, as a method of reducing excess body weight and body fat, as compared to a sham device in combination with the same lifestyle modification program.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean total body weight loss | There should be at least a 2% total body weight loss (TBWL) superiority margin between the active-product and sham-treated groups. | 6 months | 
| Categorical: proportion of participants who lose 5% total body weight | The proportion of participants who lose 5% TBWL or more in the active-product group is at least 50%, independent of the sham control | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Energy intake (kJ) | Total Energy intake (kJ) as assessed by two-day 24 hour dietary recall. | 6 months | 
| Atherogenic Index | Using lipid profile to calculate ratio of Total Cholesterol: HDL | 6 months | 
| Percentage Fat Loss | Percentage fat loss from baseline. (As measured by means of a whole body DXA scan). | 6 months | 
| High sensitivity CRP | High sensitivity CRP in mg/L | 6 months | 
| Quality of Life ratings | As assessed using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire, which is a validated self-report measure of obesity-specific quality of life in adults. The score ranges from 0 to 100, with 100 indicating the best quality of life. | 6 months | 
| Mean percent loss of baseline truncal body fat | The difference in mean percent loss of baseline truncal body fat in the active versus placebo treated groups. (As measured by a whole body DXA scan). | 6 months | 
| Mean percent loss of baseline visceral adipose tissue | The difference in mean percent loss of baseline visceral adipose tissue in the active versus placebo treated groups. (As measured by a whole body DXA scan). | 6 months | 
| Difference in lean muscle mass in the active versus placebo treated group | Difference in lean muscle mass (in grams) in the active versus placebo treated group. (As measured by the whole body DXA scan). | 6 months | 
| Difference in bone mineral content | Difference in bone mineral content (in grams) in the active versus placebo treated group. (As measured by the whole body DXA scan). | 6 months | 
| Fasting glucose | Fasting glucose in mg/dL | 6 months | 
| Glycated hemoglobin | HbA1c as a percentage | 6 months | 
| Lipid profile | Lipid profile | 6 months | 
| Blood pressure | Blood pressure in mmHg | 6 months | 
| Heart rate | Heart rate in beats per minute | 6 months | 
| Hip-waist ratio | Hip-waist ratio | 6 months | 
| Body Mass Index (BMI) in | BMI in kg/m^2 | 6 months | 
| Durability of weight loss | Maintenance of weight from 6 month timepoint (in kg) in group who discontinue active use | 12 months | 
| Sustainability of weight loss | Maintenance of weight from 6 month timepoint (in kg) in group who continue active use for entire period. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overweight, Metabolic syndrome, Weight loss, Diet, Atherogenic index, Prediabetes