Vestibular Stimulation to Trigger Adipose Loss (VeSTAL) Clinical Trial

In total there will be approximately 123 patients enrolled on the study around both sites. At
the UCSD site there will be a total of 78 total subjects (52 active treatment and 26 control
subjects) who are randomized into the treatment protocols having passed the screening
criteria. At the UU site there will be a total of 45 total subjects (30 active and 15 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 2:1 active to control allocation

- The aim of the study is to recruit a total (i.e. across both sites) of 123 participants
that pass the screening process and are randomized into the treatment protocols. With a
dropout allowance of 15% this should generate a minimum of 70 active treatment and 35
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 90 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 78 subjects who pass through screening and are randomized (52
active treatment and 26 control subjects);

- University of Ulster: a total of 45 total subjects who pass through screening and
are randomized (30 active and 15 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.

Inclusion Criteria:

1. Signed informed consent

Body mass index (BMI) ≥ 30 kg/m2, or BMI ≥ 27 kg/m2 with one or more of the below
detailed obesity related co-morbid conditions:

1. History of treatment for systemic hypertension

2. History of treatment for dyslipidemia

3. History of treatment for sleep apnea syndrome

4. Stable cardiovascular disease (no change in medication and no active events
within 1 year).

2. 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).

3. 22-80 years of age inclusive on starting the study. (In order to comply with FDA
guidance:
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm08
9740.htm#s6)

4. 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.

5. Agreement not to use of prescription, or over-the-counter, weight loss preparations
for the duration of the trial.

6. Agreement not to start smoking tobacco or marijuana for the duration of the study.

7. Access to Wi-Fi (to connect iPod to internet)

Exclusion Criteria:

1. History of vestibular dysfunction.

2. History of bariatric surgery, or gastric resection.

3. History of skin breakdown, eczema or other dermatological condition (e.g. psoriasis)
affecting the skin behind the ears.

4. History of weight loss device implantation (e.g. VBloc Maestro or Abiliti).

5. Use of a non-invasive weight loss device (e.g. Modius)

6. 6. 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).

7. Other endocrinological causes of weight gain (e.g. Cushing's disease, Cushing's
syndrome or acromegaly)

8. Previous diagnosis of HIV infection or AIDS (HIV is known to cause a vestibular
neuropathy which would prevent VeNS from working).

9. Diagnosis of cirrhosis, chronic pancreatitis, or liver, kidney or heart failure.

10. Treatment with prescription weight-loss drug therapy in the 6 months before starting
the study.

11. Tobacco or marijuana smoking in the 6 months before starting and for the duration of
the study.

12. Known genetic cause of obesity (e.g., Prader-Willi Syndrome).

13. Body weight change of more than 20% in either direction within the previous year.

14. Physician-prescribed diet, and/ or current, active member of an organized weight loss
program.

15. Diabetes mellitus (Types 1 & 2).

16. Diagnosis of epilepsy or use of anti-epileptic medication within six months of
starting the study (e.g. for the treatment of peripheral neuropathy)

17. Chronic (more than a month of daily use) treatment with opioid analgesic drugs within
the last 6 months.

18. Regular use (more than twice a month) of anti-histamine medication within the last 6
months.

19. Use of oral or intravenous corticosteroid medication within 6 months of starting the
study.

20. Use of the beta-blockers atenolol, metoprolol or propranolol within 3 months of
starting the study.

21. Current alterations in treatment regimens of anti-depressant medication for whatever
reason (including tricyclic antidepressants) (Note: stable treatment regimen for prior
6 months acceptable).

22. An active diagnosis of cancer.

23. A myocardial infarction within the preceding year.

24. 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).

25. Presence of permanently implanted battery powered medical device or stimulator (e.g.,
pacemaker, implanted defibrillator, deep brain stimulator, vagal nerve stimulator
etc.).

26. Psychiatric disorders (including untreated severe depression, schizophrenia, substance
abuse, eating disorder etc.)

27. Current participant in another weight loss study or other clinical trial.

28. Have a family member who is currently participating or is planning to participate in
this study.

29. Weight over 350 pounds as this is the weight limit of the DXA scanner.

30. Pregnancy