Effect of T6 Dermatome Electrical Stimulation on Gastric Motor Functions, Appetite, Satiation, Satiety and Weight Loss in Individuals With Overweight and Class I Obesity
Phase: NA
Conditions: Obesity
Sponsor: Mayo Clinic

 
Effect of T6 Dermatome 
Electrical Stimulation on Gastric 
Motor Functions, Appetite, 
Satiation, Satiety and Weight 
Loss in Individuals with 
Overweight and Class I Obesity 
 
NCT# NCT03261531   
 
4/18/2017 

Camilleri et al. - 1 - 
 
 
Abstract 
Background 
Previous studies demonstrated that upper abdominal dermatome electrical stimulation inhibited 
postprandial antral motility, possibly through activation of somatovisceral stimulation or central 
mechanisms. Electrical stimulation of the dorsal columns of the spinal cord to prevent the 
perception of intractable neuropathic pain signals was associated with appetite reduction and 
weight loss; percutaneous electrical neurostimulation of dermatome T6 was associated with 
appetite reduction and, along with a proper diet, achieved a significantly greater weight reduction 
than diet alone in morbidly obese subjects. The effects of T6 dermatomal electrical stimulation 
on gastric motor functions and body weight in otherwise healthy overweight or class I obese 
volunteers are unclear.  
Hypothesis 
T6 dermatomal electrical stimulation results in delay of gastric emptying of solids,reduction in 
gastric volume , inhibition of appetite, and weight loss in healthy volunteers who are overweight 
or have class I obesity. 
Aim 
In participants with BMI 25-34.99kg/m2, treated before and after two meals of the day with T6 
dermatomal electrical stimulation (delivered by a TENS unit), we aim to compare baseline 
measurements of gastric emptying of solids, fasting and postprandial gastric volume, satiation, 
satiety, appetite, and body weight with measurements after three months of treatment.   
 
 
Title of the Study: 
Effect of T6 Dermatome Electrical Stimulation on Gastric Motor 
Functions, Appetite, Satiation, Satiety and Weight Loss in 
Individuals with Overweight and Class I Obesity 
Protocol Version: 
1.4 (dated 04/18/2017) 
Principal Investigator: 
Michael Camilleri, M.D. 
Co-investigator: 
Andres Acosta, M.D., Ph.D. 
Fellow Co-investigator(s): 
Technician coordinators: 
Hoda Kadouh, Ph.D., R.D. 
 
Statistician: 
. 

Camilleri et al. - 2 - 
 
Methods 
We shall perform scintigraphic testing of gastric emptying of solids, as well as tests of satiation, 
satiety, gastric volume, appetite assessment, plasma ghrelin (total), GLP1 and PYY in 16 healthy 
overweight or class I obese volunteers receiving T6 dermatomal electrical stimulation.  
Significance 
This study will form the foundation for the potential subsequent application of dermatome 
electrical stimulation for treatment of overweight and/or class I obesity. 
Research Plan 
BACKGROUND 
An implantable gastric stimulator (gastric pacemaker) has been used to treat obesity; this 
achieves excess weight loss up to 40% in approximately 1 year. The stimulator can be placed 
laparoscopically or endoscopically, but is invasive (1-3). The modulation of neuronal activities 
and release of certain hormones with an implantable gastric stimulator may explain the reduction 
of appetite and the increase of satiety, such as a decrease in ghrelin levels (4). 
Viscerovisceral spinal sympathetic reflexes appear to play an important role in the autonomic 
control of thoracoabdominal viscera, such as the heart and great vessels (5). However, somatic 
stimulation may also affect visceral function through autonomic reflexes. The best known 
somatovisceral response is the effect of cold pain on vasomotor reactions (6). Evidence suggests 
that the gastrointestinal tract may also be influenced by such somatovisceral reflexes; thus, in 
anesthetized rats, cutaneous stimuli applied to the abdomen and hind paw decrease and increase 
stomach motility, respectively. Whereas the latter reflex response appears to relay centrally and 
the efferent limb of the reflex is located in vagal fibers, the response to abdominal stimulation 
involves a somatosympathetic reflex that relays at the level of the spinal cord, being retained in 
cervical cord-transected rats (7).  
In studies performed by the Principal Investigator 30 years ago (8), sustained somatic stimulation 
by transcutaneous electrical nerve stimulation (TENS) was applied to the skin of human 
volunteers while simultaneously monitoring their upper gastrointestinal phasic pressure activity, 
extraintestinal vasomotor indices, and plasma levels of putative humoral mediators of autonomic 
reflexes (Figure 1). 
 
 
 
 

Camilleri et al. - 3 - 
 
Figure 1.  
 
Stimuli were applied either to the hand (C8-T1) or to the upper abdomen (T5-T10) to determine 
whether impulses at these two dermatomes produced different effects on fed antral phasic 
pressure activity. TENS resulted in significant reduction (p=0.007) in antral motility index when 
applied to the hand and abdomen, as compared with sham stimulation (Figure 2). This was 
associated with increases in skin conductance and plasma beta-endorphin levels, but there were 
no changes in pulse, blood pressure, or circulating catecholamine levels. No qualitative changes 
in proximal intestinal pressure activity were detected. These studies suggested that sustained 
somatic stimuli resulted in reduced postprandial antral phasic pressure activity and the similarity 
in the responses to TENS applied to the hand and abdominal dermatomes suggests that the 
somatovisceral responses may relay at the central level. 
 Figure 2.   
 
 
 
 
While effects of TENS dermatomal stimulation on gastric emptying was not evaluated in the 
earlier studies, more recent data suggested that cutaneous gastric electrical stimulation slowed 
gastric emptying (9). Furthermore, Electrical stimulation of the dorsal columns of the spinal cord 
to prevent the perception of intractable neuropathic pain signals in two patients was associated 
with appetite reduction and weight loss (10). In a large study, Ruiz-Tovar et al. showed that 
percutaneous electrical neurostimulation of dermatome T6 was associated with appetite 
reduction and, along with a proper diet, achieved a significantly greater weight reduction than 
diet alone in morbidly obese patients (11).  

Camilleri et al. - 4 - 
 
Figure 3 shows effects on pre-treatment and post-treatment appetite scores and proportion with 
weight loss >5kg (11). 
Figure 3. 
T6 stim active     Diet alone            T6 stim active   Diet alone 
Appetite score (0-10 VAS)     
     Proportion with weight loss >5kg 
 
 
 
The effects of T6 dermatomal electrical stimulation on gastric motor functions in otherwise 
healthy overweight or class I obese volunteers are unclear.  
HYPOTHESIS AND SPECIFIC AIM 
Hypothesis 
T6 dermatomal electrical stimulation results in delay of gastric emptying of solids,reduction in 
gastric volume, inhibition of appetite, and weight loss in healthy volunteers who are overweight 
or have class I obesity. 
 
Aim 
In 16 participants with BMI 25-34.99 kg/m2, treated before and after two meals of the day with 
T6 dermatomal electrical stimulation (delivered by a TENS unit), we aim to compare baseline 
measurements of gastric emptying of solids with measurements on day 1 of treatment and after 4 
weeks and 3 months of treatment. We also aim to compare baseline measurements of fasting and 
postprandial gastric volume, satiation, satiety, appetite, and weight with measurements after 
three months of treatment.  
EXPERIMENTAL DESIGN 
 
Overweight or class I obesity participants who are not on metformin and have not been 
diagnosed with type 2 diabetes mellitus (other than dietary advice for borderline hyperglycemia) 
will be recruited for the study. 
 
Percent 

Camilleri et al. - 5 - 
 
Participants will undergo baseline measurements of height, weight, BMI, pulse, blood pressure, 
gastric function, satiation, satiety, and incretin hormones, over a period of 3 to 7 days. In an 
open-label study, all 16 participants will receive 15-minute T6 dermatome cutaneous 
stimulations with a TENS unit applied immediately before ingestion of two of the main meals of 
the day (breakfast and evening meal), and 60-minute stimulations applied immediately after 
ingestion of these meals.  
 
Participants will attend the Mayo Clinic Clinical Research Trials Unit during the first day of 
treatment, within 2 weeks from completion of baseline testing. During this visit (day 1 of 
treatment), devices will be provided and participants will receive training on self-administering 
electrical stimulation. Hence, the first set of electrical stimulations will take place at Mayo 
Clinic. On this day, participants will also undergo a gastric emptying test as a measure of the 
acute effect of T6 dermatome cutaneous stimulation on gastric emptying. 
 
Participants will apply the stimulus four times daily for a treatment period of at least 3 months, at 
the time of breakfast and evening meals (starting 15 minutes preprandially and immediately 
postprandially for 60 minutes). After 4 weeks of treatment, the participants will be asked to 
return to the Clinical Research and Trials Unit for a repeat of the gastric emptying study identical 
to the procedure performed at baseline.  During the three-month treatment period, participants 
will keep a diary of weight, measured on the same weighing scales in their homes once weekly, 
and a weekly appetite record (0-10cm VAS, paper diary).  The stimulation parameters will be: 
200 µsec pulse width at 20 Hz with a goal amplitude range of 18-20 mA. Each stimulation will 
begin at 0 mA and increase quickly to achieve the 18-20 mA dose.  Clinical trial stimulation will 
be limited to an accumulated maximum of 150 Joules each day;  For example, two 15-minute 
and two 60-minute stimulation sessions at 200 µsec pulse width, 20 Hz and 25 mA deliver an 
accumulated 40.5 Joules per day. .  Participants that do not tolerate the discomfort or develop 
nausea likely caused by the TENS unit, will report to the investigational team thepost-prandial 
duration of stimulation may be reduced from the targeted duration of 60 minutes postprandially). 
 
During the final week of the three-month treatment period or at the time of early withdrawal, 
participants will undergo the same measurements as performed during the previous gastric 
emptying test days. During these studies, participants will receive 15-minute T6 dermatome 
cutaneous stimulations with the TENS unit immediately before meal ingestion and 60-
minute stimulations immediately after meal ingestion, in the different tests. 
 
 
 
Figure 4 is a schematic that summarizes the main events that will take place in this study. 
 
Figure 4. 
 
 
 
 

Camilleri et al. - 6 - 
 
 
 
 
 
 
 
 
 
METHODS 
 
Participants 
 
Overweight or class I obese participants who are not on metformin and have not been diagnosed 
with type 2 diabetes mellitus (other than dietary advice for borderline hyperglycemia) will be 
recruited for the study. The objective is to have 16 participants complete all investigative testing 
over approximately 14 weeks. Therefore, we may screen and enroll up to 36 participants in order 
to ensure 16 fulfill eligibility criteria and complete the study. 
 
Inclusion Criteria 
 
a.   Overweight and obese adults (BMI ≥25 kg/m2 and ≤34.99 kg/m2) residing within 125 miles 
of Mayo Clinic in Rochester, MN; these will be otherwise healthy individuals with no 
unstable psychiatric disease and not currently on treatment for cardiac, pulmonary, 
gastrointestinal, hepatic, renal, hematological, neurological, or endocrine (other than 
hyperglycemia on diet) disorders. 
b.   Age: 18-65 years   
c.   Gender: Men or women. Women of childbearing potential will be using an effective form of 
contraception, and have negative pregnancy tests within 48 hours of enrollment and before 
each radiation exposure. 
d.   Subjects must have the ability to provide informed consent before any trial-related activities. 
 
Eligible individuals will be asked to avoid taking additional medications and supplements for the 
duration of the study, unless reviewed and approved by the study team.   
 
Exclusion Criteria 
 
a.   Abdominal surgery other than appendectomy, Caesarian section or tubal ligation  

Camilleri et al. - 7 - 
 
b.   Positive history of chronic gastrointestinal diseases, systemic disease that could affect 
gastrointestinal motility, or use of medications that may alter gastrointestinal motility, 
appetite or absorption, e.g., Orlistat  
c.   Positive history of diabetes mellitus or use of hypoglycemic medications 
d. Positive history of spinal cord injury and/or chronic back pain 
e.   Significant untreated psychiatric dysfunction based upon screening with the Hospital Anxiety 
and Depression Inventory (HAD) (12), a self-administered alcoholism screening test 
(AUDIT-C) (13), and the Questionnaire on Eating and Weight Patterns (binge eating 
disorders and bulimia) (14). If such a dysfunction is identified by a HAD score >11 or 
difficulties with substance or eating disorders, the participant will be excluded and given a 
referral letter to his/her primary care doctor for further appraisal and follow-up.   
f.   Intake of medication, whether prescribed or over the counter (except multivitamins), within 7 
days of the study. Exceptions are birth control pill, estrogen replacement therapy, thyroxine 
replacement therapy, low dose analgesia or anti-inflammatory medications (Acetaminophen 
and Ibuprofen) and any medication administered for co-morbidities as long as they do not 
alter gastrointestinal motility including gastric emptying and gastric accommodation. 
g.   Subjects may also be excluded from participation for other factors at the discretion of the 
principal investigator. 
 
Recommended Diet (modified from ref. 11) 
 
The Participants will be encouraged to consume a diet of 1200 kcal for women and 1400 kcal for 
men (estimated mean macronutrient proportions: carbohydrates 51%; proteins 23%; fats 26%). 
Upon enrollment in the study, they will meet with a registered dietitian for a pertinent diet 
education. Throughout the duration of the study, the participants will record their food intake on 
a daily food diary that will be reviewed by the study dietitian. 
 
1200 Kcal: 
 
Breakfast: Skimmed milk (240ml) or two natural yogurts - bread (100g) or two cookies – 
granola or whole grain cereal (1/2 cup) – nuts (15 mixed) 
Mid morning: Fruit (100g of apple, pear, orange, peach, or kiwi)  
Lunch and dinner:  
First course to choose from:  
• Vegetables (200g) spinach, chard, eggplant, watercress, endive, lettuce, cauliflower, 
mushrooms, leeks, asparagus, cabbage, cucumber, peppers, tomatoes, alternating cooked or salad  
• Vegetables (150g) green beans, beets, carrots, artichokes or brussel sprouts  
• Vegetable soup (1 cup) 
• Pasta, semolina or rice (1/3 cup cooked)  
Second course to choose from:  
• Fish (120g)  
• Chicken, turkey, rabbit, veal (100g)  
• Two eggs   
Bread (30 g) 
Dessert, choice of:  

Camilleri et al. - 8 - 
 
• Fruit (100g of apple, pear, orange, peach, or kiwi OR 200g melon, watermelon, or strawberries) 
• Snack: 200ml of skimmed milk alone or with coffee or tea  
Olive oil for the entire day: 30ml (2 tablespoons)  
1400 Kcal: 
 
Breakfast: Skimmed milk (240ml) or two natural yogurts - bread (100g) or two cookies - 
cottage cheese (60 g) - granola or whole grain cereal (1/2 cup) – nuts (15 mixed) 
Mid morning: Fruit (100g of apple, pear, orange, peach, or kiwi)  
Lunch and dinner:  
First course to choose from:  
• Vegetables (250g) spinach, chard, eggplant, watercress, endive, lettuce, cauliflower, 
mushrooms, leeks, asparagus, cabbage, cucumber, peppers, tomatoes, alternating cooked or salad  
• Vegetables (200g) green beans, beets, carrots, artichokes or brussel sprouts  
• Vegetable soup (1 cup) 
• Pasta, semolina or rice (1/2 cup cooked)   
Second course to choose from:  
• Fish (160g)  
• Chicken, turkey, rabbit, veal (130g)  
• Two eggs with cheese   
Bread (30 g) 
Dessert, choice of:  
• Fruit (100g of apple, pear, orange, peach, or kiwi OR 200g melon, watermelon, or strawberries)  
Snack: 200ml of skimmed milk alone or with coffee or tea – Corn flakes (1/2 cup)  
Olive oil for the entire day: 30ml (2 tablespoons)  
 
T6 Dermatomal Stimulation  
 
T6 dermatomal stimulation will be achieved by utilizing an Elira TENS device (Elira 
Therapeutics, Inc., St. Louis, MO), following the company’s protocol. The Elira device provides 
a broad range of options for stimulation parameters.  In particular, pulse width is programmable 
from 25 µsec to 400 µsec, pulse amplitude from 1 mA to 45 mA, pulse frequency from 1 Hz to 
200 Hz, session duration from 5 min to 60 min, and number of sessions per day from 0 to 8 
sessions.  
• Participants will undergo four stimulation sessions per day (daily for at least 3 months) 
distributed around 2 meals (breakfast and dinner) as follows: A 15-minute pre-prandial 
session (starting 15 minutes before the meal) and a 60-minute post-prandial session (starting 
immediately after the meal), during which the participant can walk around and continue to 
perform regular activities as desired, with the exception of driving and operating machinery 
• The stimulation parameters will be: 200 µsec pulse width at 20 Hz with a goal amplitude 
range of 18-20 mA (depending on the subject’s pain threshold). Participants will be 
instructed to begin each stimulation at 0 mA and increase as tolerated (within 5 minutes) to 
achieve the 18-20 mA goal. 

Camilleri et al. - 9 - 
 
Clinical trial stimulation will be limited to an accumulated maximum of 150 Joules per day, with 
a maximum of 0.001 Joules (1 mJ) per pulse. For example, two 15-minute and two 60-minute 
stimulation sessions at 200 µsec pulse width, 20 Hz and 25 mA deliver an accumulated 40.5 
Joules per day, with only 0.23 mJ per pulse, allowing for upward titration as needed. The 
principal investigator may increase or decrease any of the stimulation parameters at his 
discretion up to the maximum 150 Joules daily limit.  
Blood Samples 
 
Fasting, 15, 45, and 90 minute post-prandial blood samples will be collected at the baseline and 
treatment conclusion visits, and will be stored at -70°C for assay analysis of plasma 
gastrointestinal hormone levels as well as storing a blood-based DNA sample for possible future 
genetic testing. Fasting blood glucose will be measured at one of the baseline visits using a 
glucometer (CRTU nurses). 
 
 
 
Quantitative Traits  
 
On different days, participants will attend Mayo Clinic Clinical Research Trials Unit at a 
prescheduled time after an 8-hour fasting period, and the following validated quantitative traits 
will be measured. 
 
1.  Gastric emptying (GE) of solids by scintigraphy:  Scans will be obtained immediately after 
consumption of test meal and then every 15minutes for the first hour, every 30 minutes for the 
second hour and then at the 3 and 4 hour timepoints. The primary endpoint is gastric half-
emptying time (GE T1/2), and the secondary endpoints are proportions emptied at 2 and 4 hours 
(15). The normal range for GE T1/2 is based on 10th and 90th percentiles in healthy volunteers, 
based on gender (16). In general, GE of liquids is noncontributory in the context of upper 
gastrointestinal symptoms (17). In order to reduce radiation burden (needing two isotopes to 
assess both liquid and solid emptying), we will study exclusively GE of solids.   
 
Figure 5 
2.  Fasting and postprandial gastric 
volume (GV) by single photon emission 
computed tomography (SPECT), 
developed and validated (including 
performance characteristics) in our lab 
[Figure 5 (18-20)].  
 
3.  Satiation by Ensure® nutrient drink test 
(1kcal/mL, 11% fat, 73% carbohydrate, 
16% protein) with ingestion at a rate of 120 
mL every 4 minutes equivalent to a constant rate of 30ml/minute to measure volume to fullness 
(VTF) and maximum tolerated volume (MTV) (21). Briefly, participants record their sensations 
of fullness using a numerical scale from 0 to 5, with level 0 being no symptoms, level 3 

Camilleri et al. - 10 - 
 
corresponding to fullness sensation after a typical meal (“volume to fullness”), and level 5 
corresponding to the MTV (maximum or unbearable fullness/satiation). Nutrient intake is 
stopped when subjects reach the score of 5. Postprandial symptoms of fullness, nausea, bloating, 
and pain are measured 30 minutes after the meal using 100mm horizontal visual analog scales 
(VAS), with the words “none” and “worst ever” anchored at each end. 
 
4.  Satiety- Buffet Meal (for assessment of kcal intake as a measure of appetite) by ad-
libitum buffet meal to measure total caloric intake and macronutrient distribution in the chosen 
food (15). Five hours after ingesting 300mL liquid nutrient (Ensure®) as part of the SPECT 
gastric volume study, participants will be invited to eat, during a 30-minute period, a standard ad 
libitum meal that includes five cheese lasagna (Stouffers®, Nestle USA, Inc., Solon, OH 
[nutritional analysis of each 304g box: 340kcal (19g protein ((23% of energy)), 41g carbohydrate 
((48% of energy)), and 11g fat ((29% of energy))]); vanilla pudding (Jell-O®, Kraft Foods North 
America, Tarrytown, NY [nutritional analysis of each 110-g carton: 110 kcal (1g protein ((4% of 
energy)), 23g carbohydrate ((84% of energy)), and 1.5g fat ((12% of energy))]); and skim milk 
(Kemps Select, Kemps LLC®, St. Paul, MN [nutritional analysis of each 236mL carton: 90kcal 
(9g protein ((40% of energy)), 13g carbohydrate ((60% of energy)), and 0g fat))]). The total 
amount (grams and kilocalories) of food consumed and the kilocalories of each macronutrient at 
the ad libitum meal are analyzed by the study dietitian using validated methods.  
Participants will be subdivided into “excessive eaters” [the top tertile (1176 kcal) as 
defined in a prior study of 264 overweight or obese participants] and the bottom 2 tertiles, 
defining non-excessive intake among overweight or obese participants.  
 
5.  Ratings of appetite will be measured every 30 minutes between the time of ingestion of 
standard liquid breakfast and the start of the ad libitum meal. Ratings for appetite (satiety, 
fullness, hunger and prospective food consumption), thirst, wellbeing and nausea will be 
recorded using VAS, as described by Flint et al. (22). VAS, 100mm in length with words 
anchored at each end expressing the most positive and the most negative ratings, will be used to 
assess hunger, satiety, fullness, prospective food consumption, desire to eat something fatty, 
salty, sweet or savory, and the palatability (5 questions) of the test meal (Figure 6). 
 
 
 
Overall appetite score will be calculated as the 
average of the four individual scores (satiety + 
fullness + 100-prospective food consumption + 
100-hunger / 4. 
 
6.  Plasma gastrointestinal hormones (ghrelin, 
GLP-1 and PYY) by radioimmunoassay measured 
at fasting, and 15, 45, and 90 minutes 

Camilleri et al. - 11 - 
 
postprandially during the NDT. The primary endpoint is the peak postprandial level. CCK levels 
will not be measured in the current study, since they were non-informative in our prior studies. 
Total ghrelin will be measured by a radioimmunoassay technique (Linco Research, Inc., St. 
Charles, MO). The assay uses 125I-labeled ghrelin and a ghrelin antiserum to determine the level 
of total ghrelin in plasma.GLP-1 will be measured as the biologically active GLP-1 (active and 
total) using a 2-site non-competitive immunoassay based on enzyme-labeled quantification of 
GLP-1 detected by a fluorogenic substrate. PYY will be measured by radioimmunoassay (Linco 
Research, Inc., St. Charles, MO). PYY exists in at least 2 molecular forms, 1-36 and 3-36, both 
of which are physiologically active and are detected by the assay.    
7.  Self-administered questionnaires assessing affect, exercise performance, attitudes, 
satisfaction with body image, and eating behavior (12-14,23-26). 
 
 
 
 
Statistical Analysis 
 
Sample size assessment - Sample size assessment is based on the results of primary endpoints in 
the Mayo Clinic lab. Assuming the intra-individual coefficient of variation (or standard 
deviation) is similar to the inter-individual variation, we have used the SDinter for estimating the 
power of the study (n=16, baseline versus post-treatment).  
 
Response 
Mean 
SD 
Predicted detectable effect size (%(absolute #)),  n=16 
on treatment compared to baseline, paired analysis  
Gastric emptying, T1/2 min* 
121.7 
29.8 
18.4%  (22.4 min) 
Fasting gastric volume, ml** 
225 
65 
21.8%  (49mL) 
Gastric accommodation, ml** 
507 
100 
14.7% (75mL) 
Data obtained from *ref. 16 and **ref. 20; predicted detectable effect size is shown with 80% power, α=0.05.  
 
The sample size of 16 on-treatment relative to baseline will have sufficient power to detect a 
difference in gastric emptying of 22.4 min, of fasting gastric volume of 49mL, and in gastric 
accommodation of 75mL. 
 
Statistical Methods 
 
It is anticipated that all primary and secondary endpoints will be normally distributed. We shall 
use a paired student’s t-test to compare study parameters (differences between baseline and on-
treatment). An analysis of covariance may be examined using gender and BMI as covariates, 
since these may significantly affect gastric functions such as satiation, maximum tolerated 
volume, and gastric emptying.  
 
Interim Analysis 
An administrative interim analysis will be completed after 6 subjects have completed at least 4 weeks of 
treatment.  The data will be submitted in a blinded fashion to the study sponsor’s statistician while the 
investigative team remains blinded to the treatments.  This interim analysis will be conducted for 
administrative purposes to provide information about future planning of other research activities.  The 

Camilleri et al. - 12 - 
 
conduct of this study will not be altered and all planned research activities will proceed until the 
completion of the targeted 16 subjects. 
Primary endpoints  
1. Body weight change from baseline  
2. Gastric emptying T1/2 after day 1 treatment 
3.  Gastric emptying T1/2 after 3 months treatment 
 
Secondary endpoints  
1. Fasting gastric volume  
2. Postprandial gastric volume or accommodation volume 
3. Gastric emptying % at 1 hour in day 1 and end of three months of treatment 
4. Satiation: volume to fullness (grade 3) and maximum tolerated volume (grade 5) 
5. Satiety: kcal intake at buffet meal 
6. Appetite score during satiety meal test and at weekly intervals (at home) 
7. Plasma ghrelin, GLP-1 and PYY fasting 
8. Peak postprandial plasma ghrelin, GLP-1 and PYY fasting 
 
Anticipated Results and Significance  
 
We anticipate greater weight loss with active treatment with dermatomal stimulation compared 
to baseline. The sample size is not sufficient to appraise twice versus once daily treatment. 
However, the data will be tabulated for descriptive analysis. The physiological measurements 
will provide information about the potential mechanisms involved in any beneficial effects on 
weight and appetite. 
 
Potential Pitfalls, Precautions Taken, and Alternative Strategies 
 
a. Feasibility - Given our 500-person database with baseline quantitative traits and genotype, 
we are confident we will recruit sufficient numbers of participants for these studies that 
involve mainly noninvasive tests. 
b. The pilot study is intended to document feasibility to recruit and retain subjects in such a 12 
to 14-week, hypothesis-generating treatment trial, and to appraise the weight loss achieved in 
order to characterize the coefficient of variation for planning the sample size of a future 
hypothesis testing trial. 
c. Exploratory analyses will be performed using the other quantitative traits which are all 
measured in these studies to assess physiological parameters that may be relevant to any 
beneficial effects of the treatment in these overweight or class I obese subjects. 
d. In order to develop pre-specified monitoring and analysis plans, we shall establish a DATA 
SAFETY MONITORING PLAN which will involve review by experts independent of the 
study, using a team comprised of researchers with track records in biostatistics and clinical 
trials and expertise in the quantitative biomarker 
 
Device Safety: Designation of Non-Significant Risk 
 

Camilleri et al. - 13 - 
 
Based on the FDA guidance on Significant Risk and Nonsignificant Risk Medical Device 
Studies (27), the proposed study does not meet the definition for a significant risk (SR) device 
study and hence is a non-significant risk (NSR) clinical study.  
 
Moreover, the Elira TENS device is regarded as an NSR device on the following basis:  
 
• It is not implantable 
• It does not support or sustain human life 
• It is not for use of substantial importance in diagnosing, curing, mitigating or treating a 
disease (no claims related to obesity have been made by the manufacturer) 
• It does not present a potential for serious risk to the health, safety or welfare of the 
participant   
 
It is important to note that the Elira TENS device is essentially similar to commercially-
available, over-the-counter TENS units that can be purchased at local pharmacies and are 
commonly utilized for self-administered therapy.  
 
Lastly, participants will keep a diary that will serve as a tool for evaluating risk/discomfort 
potentially associated with the use of the Elira TENS unit. Nausea, dyspepsia and local 
discomfort on anterior abdominal wall (treatment site) may occur with over-stimulation.  
 
 

Camilleri et al. - 14 - 
 
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