Vestibular Stimulation to Trigger Adipose Loss (VeSTAL) Clinical Trial

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

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).

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 all 4 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.
• Masking: Double Blind (Subject, Nursing staff, Dietician, Co-coordinators, Outcomes Assessor and any other study staff who have contact with the subject)
• Data from all sites will be collated at the end of the studies and analysis will be performed on one data set.

This protocol governs the activities at both the USA and NI/UK clinical sites.

Inclusion Criteria:

1. Signed informed consent
2. Body mass index BMI ≥ 27 kg/m2.
3. 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).
4. 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)
5. 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.
6. Agreement not to use of prescription, or over-the-counter, weight loss preparations for the duration of the trial.
7. Agreement not to start smoking tobacco or marijuana

Exclusion Criteria:

1. History of vestibular dysfunction or other inner ear disease as indicated by the screening questions.
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. 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 smoking (including vaping) in the six months prior to starting and for the duration of the study.
12. Use of marijuana (smoking, vaping or in edible form) more than twice a month on average.
13. Known genetic cause of obesity (e.g., Prader-Willi Syndrome).
14. Body weight change of more than 20% in either direction within the previous year.
15. Physician-prescribed diet, and/ or current, active member of an organized weight loss program.
16. Diabetes mellitus (Types 1 & 2).
17. Diagnosis of epilepsy or use of anti-epileptic medication within six months of starting the study (e.g. for the treatment of peripheral neuropathy)
18. Chronic (more than a month of daily use) treatment with opioid analgesic drugs within the last 6 months.
19. Regular use (more than twice a month) of anti-histamine medication within the last 6 months.
20. Use of oral or intravenous corticosteroid medication within 6 months of starting the study.
21. Use of the beta-blockers atenolol, metoprolol or propranolol within 3 months of starting the study.
22. Current alterations in treatment regimens of anti-depressant medication for whatever reason (including tricyclic antidepressants) (Note: stable treatment regimen for prior 6 months acceptable).
23. An active diagnosis of cancer.
24. A myocardial infarction within the preceding year.
25. 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).
26. Presence of permanently implanted battery powered medical device or stimulator (e.g., pacemaker, implanted defibrillator, deep brain stimulator, vagal nerve stimulator etc.).
27. Psychiatric disorders (including untreated severe depression, schizophrenia, substance abuse, eating disorder etc.)
28. Current participant in another weight loss study or other clinical trial.
29. Have a family member who is currently participating or is planning to participate in this study.
30. Weight over 350 pounds at UU, TDE and CTRI site (as this is the weight limit of the DXA scanner) or a weight over 500 pounds at the EPARC site (as this is the weight limit of the DXA scanner)
31. Pregnancy The decision to exclude participants with type 2 diabetes mellitus was made after reading the FDA's draft guidance (see: http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071612.pdf). This notes that, "[c]compared with nondiabetic patients, overweight and obese patients with type 2 diabetes often respond less favorably to weight-management products and may face unique safety issues such as risk for sulfonylurea-induced hypoglycemia following weight loss (if the dose of sulfonylurea is not appropriately lowered or the drug discontinued)." The FDA then go on to advise "examining the efficacy and safety of weight-management products in trials dedicated to patients with type 2 diabetes." On the basis of this advice we made the decision to exclude patients with type 2 diabetes. This is an important patient group of course, and our intention is to investigate type 2 diabetics in due course.

If a subject is found to possibly have type 2 diabetes during the initial screening, then they will be excluded and asked to notify their primary care physician. However, if a subject passes the initial screening but a suspicion of this diagnosis arises during one of the study tests, then the subject will be asked to notify their primary care physician, though they will still be allowed to complete the study.