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There is an ongoing and worsening problem with obesity in the developed, and much of the developing world. Although it has long been realized that Western diets that are rich in sugar and fat play an important role in this, it has only recently been realized that exposure to these diets, particularly in childhood, can damage the part of the brain that determines how much fat there is in the body. The result of this damage is that the so-called "set-point" for fat in this part of the brain is pushed upwards. There is a lot of evidence from animals that activating the brain's balance (vestibular) system pushes this set-point for fat downwards to cause fat loss, probably because this "tricks" the brain into thinking that there is increased physical activity. The aim of this study is to see whether non-invasive electrical stimulation of the vestibular system in human participants causes a change in metabolism of fat and/or energy expenditure, which, if regulated upwards, would suggest this could be used as a means of reducing body fat in humans.
There is a growing realization that obesity can, in many ways, be viewed as a neurological disease triggered by lifestyle factors. There is clear evidence that the central melanocortin system, which is centered in the arcuate nucleus of the hypothalamus, regulates a "set-point" for how much fat the body should have. It does so by altering appetite and metabolic rate so that deviations too far in either direction are strongly resisted. This set-point is determined by genetic, epigenetic and lifestyle factors. Thus, excessive exposure to dietary monosaccharides, such as glucose, and saturated fats, especially in childhood and adolescence, can damage the neurons of the arcuate nucleus and push the set-point up. This then can condemn sufferers to a lifetime of obesity, despite individual efforts to combat it using diet and/or exercise.
Establishing a method of tuning down the set-point for body fat thus has to be a goal if the current obesity pandemic is to be successfully combatted. A significant amount of animal work suggests that stimulating the vestibular system in the inner ear, by means of chronic centrifugation, actually does just that and causes a reduction in body fat. This is likely because chronic vestibular activation is taken by the brain to represent a state of increased physical activity, and in order to optimize homeostasis it would be appropriate for the body to have a leaner physique, by reducing unnecessary energy expenditure from carrying excess fat.
It is possible to stimulate the vestibular nerve in humans by applying a small electrical current to the skin behind the ears. This is an established technology that is believed to be safe, but only previously used for research purposes. The investigators found in a pilot study that recurrent stimulation of this kind for two or three hours a week over four months led to a statistically significant reduction in truncal fat in the active group as opposed to the control group who underwent sham stimulation.
Given the current, and increasing levels of global obesity, it is important to determine whether non-invasive electrical vestibular nerve stimulation (VeNS), otherwise known as galvanic vestibular stimulation (GVS), is a viable treatment option, since if it were this would be of significant scientific importance.
The investigators wish to use the technique of indirect calorimetry to explore this. This involves wearing a tight face mask to collect all inspired oxygen and expired carbon dioxide and using formulae to calculate total energy expenditure and the component of metabolism that is derived from fat as compared to carbohydrate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment then sham | Experimental | 20 subjects will be randomised to first receive active vestibular nerve stimulation during indirect calorimetry. Then 2 weeks later they will return for sham stimulation during indirect calorimetry. |
|
| Sham then treatment | Experimental | 20 subjects will be randomised to first receive sham stimulation during indirect calorimetry. Then 2 weeks later they will return for active vestibular nerve stimulation during indirect calorimetry. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vestibular Nerve Stimulator | Device | Electrical stimulation of the vestibular nerve with vestibular nerve stimulator (GVS device) for for 45 minutes using binaural mastoid placement. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Fat Consumption (During VeNS) | Change in percent fat utilization from baseline as measured using indirect calorimetry. | During middle 15 minutes of 45 minute vestibular nerve stimulation session |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Energy Expenditure (During VeNS) | Change in energy expenditure from baseline in kcal/min as measured using indirect calorimetry. | During middle 15 minutes of 45 minute vestibular nerve stimulation session |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Diego | San Diego | California | 92093 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Then Sham | 20 subjects will be randomised to first receive active vestibular nerve stimulation during indirect calorimetry. Then 2 weeks later they will return for sham stimulation during indirect calorimetry. Vestibular Nerve Stimulator: Electrical stimulation of the vestibular nerve for for 45 minutes using binaural mastoid placement. Sham stimulator: Looks identical to vestibular nerve stimulator but discharges current into an internal resistor rather than activating the vestibular nerves. |
| FG001 | Sham Then Treatment | 20 subjects will be randomised to first receive sham stimulation during indirect calorimetry. Then 2 weeks later they will return for active vestibular nerve stimulation during indirect calorimetry. Vestibular Nerve Stimulator: Electrical stimulation of the vestibular nerve for for 45 minutes using binaural mastoid placement. Sham stimulator: Looks identical to vestibular nerve stimulator but discharges current into an internal resistor rather than activating the vestibular nerves. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Active Then Sham | 20 subjects will be randomised to first receive active vestibular nerve stimulation during indirect calorimetry. Then 2 weeks later they will return for sham stimulation during indirect calorimetry. Vestibular Nerve Stimulator: Electrical stimulation of the vestibular nerve for for 45 minutes using binaural mastoid placement. Sham stimulator: Looks identical to vestibular nerve stimulator but discharges current into an internal resistor rather than activating the vestibular nerves. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Fat Consumption (During VeNS) | Change in percent fat utilization from baseline as measured using indirect calorimetry. | Posted | Mean | Standard Deviation | % of fat as metabolic substrate | During middle 15 minutes of 45 minute vestibular nerve stimulation session |
|
During 2 hour period of each both visits.
No adverse events were recorded in this pilot study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Then Sham | 20 subjects will be randomised to first receive active vestibular nerve stimulation during indirect calorimetry. Then 2 weeks later they will return for sham stimulation during indirect calorimetry. Vestibular Nerve Stimulator: Electrical stimulation of the vestibular nerve for for 45 minutes using binaural mastoid placement. Sham stimulator: Looks identical to vestibular nerve stimulator but discharges current into an internal resistor rather than activating the vestibular nerves. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Paul McGeoch | UCSD | 858-232-3312 | pdmcgeoch@ucsd.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 25, 2017 | Jun 10, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D024821 | Metabolic Syndrome |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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Double-blind
| Sham stimulator | Device | Looks identical to vestibular nerve stimulator but discharges current into an internal resistor rather than activating the vestibular nerves. |
|
| BG001 | Sham Then Active | 20 subjects will be randomised to first receive sham stimulation during indirect calorimetry. Then 2 weeks later they will return for active vestibular nerve stimulation during indirect calorimetry. Vestibular Nerve Stimulator: Electrical stimulation of the vestibular nerve for for 45 minutes using binaural mastoid placement. Sham stimulator: Looks identical to vestibular nerve stimulator but discharges current into an internal resistor rather than activating the vestibular nerves. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
20 subjects will be randomised to first receive sham stimulation during indirect calorimetry. Then 2 weeks later they will return for active vestibular nerve stimulation during indirect calorimetry. Vestibular Nerve Stimulator: Electrical stimulation of the vestibular nerve for for 45 minutes using binaural mastoid placement. Sham stimulator: Looks identical to vestibular nerve stimulator but discharges current into an internal resistor rather than activating the vestibular nerves. |
|
|
| Secondary | Change in Energy Expenditure (During VeNS) | Change in energy expenditure from baseline in kcal/min as measured using indirect calorimetry. | Posted | Mean | Standard Deviation | kcal/min | During middle 15 minutes of 45 minute vestibular nerve stimulation session |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | Sham Then Treatment | 20 subjects will be randomised to first receive sham stimulation during indirect calorimetry. Then 2 weeks later they will return for active vestibular nerve stimulation during indirect calorimetry. Vestibular Nerve Stimulator: Electrical stimulation of the vestibular nerve for for 45 minutes using binaural mastoid placement. Sham stimulator: Looks identical to vestibular nerve stimulator but discharges current into an internal resistor rather than activating the vestibular nerves. | 0 | 20 | 0 | 20 | 0 | 20 |
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| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007333 | Insulin Resistance |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |