Effect of T6 Dermatome Electrical Stimulation on Gastroduodenal Motility in Healthy Volunteers
Phase: NA
Conditions: Weight Loss
Sponsor: Mayo Clinic

 
 
Effect of T6 Dermatome 
Electrical Stimulation on  
Gastroduodenal Motility in 
Healthy Volunteers 
 
NCT03316105 
 
5/15/2017 

Camilleri et al. - 1 - 
 
 
Abstract 
Background 
Previous studies demonstrated that electrical stimulation in the upper abdomen inhibited 
postprandial antral motility, possibly through activation of somatovisceral stimulation or central 
mechanisms. 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 effect on appetite and weight could be related to 
an effect on gastric motor functions. However, the effects of T6 dermatomal electrical 
stimulation on gastric motor functions are unclear.  
Hypothesis 
T6 dermatomal electrical stimulation treatment results in inhibition of postprandial antral 
motility in healthy volunteers. 
Aim 
We aim to compare measurements of postprandial antral motor activity in healthy participants 
treated with sham versus active T6 dermatomal electrical stimulation (delivered by a TENS unit).   
Methods 
We shall perform multilumen gastroduodenal manometry to measure postprandial antral motor 
activity in response to sham versus active T6 dermatomal electrical stimulation in a parallel 
group study design. 
Significance 
This study will form the foundation for the potential subsequent application of dermatome 
electrical stimulation for altering gastroduodenal motility. 
Title of the Study: 
Effect of T6 Dermatome Electrical Stimulation on  
Gastroduodenal Motility in Healthy Volunteers 
Protocol Version: 
2.0 (dated 5/15/2017) 
Principal Investigator: 
Michael Camilleri, M.D. 
Fellow Co-investigator(s): 
Technician coordinators: 
Hoda Kadouh, Ph.D., R.D., Victor Chedid, M.D. 
Irene Busciglio, B.S.; Duane Burton, M.H.A.; Michael Ryks ; 
Deborah Eckert BSN; Kayla Arndt  
Statistician: 
Alan R. Zinsmeister, Ph.D. 

Camilleri et al. - 2 - 
 
 
Research Plan 
BACKGROUND 
A surgically implantable gastric stimulator (gastric pacemaker) has been used to treat obesity; 
this achieves excess weight loss up to 40% in approximately 1 year (1). 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 
(2). 
Viscerovisceral spinal reflexes that are thought to be relayed through sympathetic pathways 
appear to play an important role in the autonomic control of thoracoabdominal viscera, such as 
the heart and great vessels (3). 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 (4). 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 (5).  
In studies performed by the Principal Investigator 30 years ago (6), 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). 
Figure 1.  

Camilleri et al. - 3 - 
 
 
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 (suggesting vasomotor changes) and plasma beta-
endorphin levels (suggesting a central stress pathway was stimulated), 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. It is assumed that such a central effect results in 
inhibition of firing of vagal cholinergic pathways that are typically stimulated in the post-
prandial period by the presence of food in the stomach activating vagal afferents 
 Figure 2.   
 
 
 
 
 
 
 

Camilleri et al. - 4 - 
 
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 (7). 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 (8). The mechanism of appetite reduction in response to treatment is unknown, but could 
be explained by a possible effect on gastric motor functions. 
The effects of T6 dermatomal electrical stimulation on gastric motor functions, particularly 
gastroduodenal motility, are unclear.  
 
 
HYPOTHESIS AND SPECIFIC AIM 
Hypothesis 
T6 dermatomal electrical stimulation treatment results in inhibition of postprandial antral 
motility in healthy volunteers. 
Aim 
We aim to compare measurements of postprandial antral motor activity in 16 healthy participants 
treated with sham versus active T6 dermatomal electrical stimulation (delivered by a TENS unit).   
 
EXPERIMENTAL DESIGN 
 
Healthy volunteers will be recruited for this one-day study that will take place in our gastric 
functions laboratory at the Clinical Research Trials Unit (CRTU) at Mayo Clinic. Participants 
will have a multilumen gastroduodenal manometry tube placed transnasally after overnight 
fasting.  
 
In a parallel group design, all 16 participants will receive a standardized breakfast meal to assess 
baseline post-prandial gastric motility followed by ingestion of the same standardized meal as 
lunch (500 kcal, see Appendix 1) at 4 hours after the ingestion of the first (breakfast) meal.  Prior 
to the lunch meal, the subjects will receive either sham or active T6 Dermatome cutaneous 
stimulations with a wireless TENS unit applied 15 minutes  before ingestion of  the  lunch meal, 
and immediately after completing ingestion of this meal for a duration of 60 minutes. 
Participants will be randomized to either sham or active treatment at the lunch meal. Hence, 8 
participants will receive one set of sham stimulations (pre and post prandial in relation to lunch 
time meal) and 8 participants will receive one set of active stimulations (pre and post prandial in 
relation to lunch time meal). Participants randomized to sham will have a TENS unit connected 
without activation of the electrodes. 
 

Camilleri et al. - 5 - 
 
Gastroduodenal manometry will be performed to assess gastroduodenal motility during the 
postprandial phase of each meal, with the primary measurement being the antral motility index 
during the first postprandial hour.  
 
METHODS 
 
Participants 
 
At least 16 healthy volunteers will be recruited for the study. We may screen up to 24 
participants in order to ensure 16 fulfill eligibility criteria and complete the study. Additional 
participants from our list of eligible candidates will be recruited to replace early withdrawals, in 
the event that participants withdraw on testing day before having completed all investigative 
testing.  Participants will be randomized in blocks of four. 
 
Inclusion Criteria 
 
a.   Healthy volunteers with BMI ≤34.99 kg/m2 residing within 125 miles of Mayo Clinic in 
Rochester, MN; these will be 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 the test day. 
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 
one week before and after the test day, unless reviewed and approved by the study team.   
 
Exclusion Criteria 
 
a.   Abdominal surgery other than appendectomy, Caesarian section or tubal ligation.  
b.   Positive history of chronic gastrointestinal diseases, systemic disease that could affect 
gastrointestinal motility, or use of medications that may alter gastrointestinal motility. 
c. Positive history of spinal cord injury and/or chronic back pain. 
d.   Significant untreated psychiatric dysfunction based upon screening with the Hospital Anxiety 
and Depression Inventory (HAD) (9) If such a dysfunction is identified by a HAD score >11 
on either Anxiety or Depression 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.   
e.   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. 
f.   Subjects may also be excluded from participation for other factors at the discretion of the 
principal investigator. 

Camilleri et al. - 6 - 
 
 
  
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 device 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 randomized to active treatment will undergo 2 stimulation sessions related to 
lunch meal, 4 hours after consuming a standardized breakfast meal and acquiring baseline 
assessment of post-prandial gastric motility.  The stimulation session will occur as follows: A 
15-minute pre-prandial session (starting 15 minutes before the meal) and a 60-minute post-
prandial session (starting immediately after completing ingestion of the meal) 
• The stimulation parameters will be: 200 µsec pulse width at 30 Hz and 40mA to achieve a 
stimulation  goal amplitude range of 18-30 mA (depending on the subject’s skin impedence 
and pain threshold). Each stimulation will begin at 0 mA and increase quickly to achieve the 
18-30 mA.   
Clinical trial stimulation will be limited to an accumulated maximum of 20.25 Joules on the test 
day;  one 15-minute and one 60-minute stimulation sessions at 200 µsec pulse width, 30 Hz and 
40 mA deliver an accumulated 20.25 Joules.  
Antral Motor Activity  
 
On the test day, participants will attend Mayo Clinic Clinical Research Trials Unit at a 
prescheduled time after an 8-hour fasting period, and the following validated test will be 
performed following both the standardized breakfast and lunch meals. 
 
 
Gastroduodenal manometry 
 
Gastroduodenal tube placement: Participants will undergo an overnight (8 hours) fast. 
Trained technologist (DB) and staff physician (MC) will perform the placement in accordance 
with standard practice over the past 25 years. A 4-meter Teflon (green) guidewire will be placed 
in the duodenum in order to facilitate placing the combined manometry tube into the duodenum. 
The position of the manometry tube will be verified using fluoroscopy.  
Figure 3. Multilumen manometric assembly in the upper gastrointestinal 
tract to measure distal antral motility in postprandial period 
Gastroduodenal manometry: Gastrointestinal manometry will be 
performed after an overnight fast with a multiple-lumen perfusion tube 

Camilleri et al. - 7 - 
 
(external diameter: 6mm) that is introduced along a guidewire placed with aid of fluoroscopy. 
Each of the fifteen perfusion channels of the manometric tube will be perfused with distilled 
water via a pneumohydraulic pump (perfusion rate: 0.15ml/min, perfusion pressure: 14psi) and 
attached to a strain gauge transducer (model PX-MK099, Edwards Lifesciences, Irvine, CA.). One 
side opening was made in each channel of the multi-lumen tube, and the positions of these 
openings were at the tip of the tube will be fluoroscopically placed across the antroduodenal 
region; thus, the tip of the tube lies near the ligament of Treitz. Fasting pressure activity will be 
recorded in each volunteer for 1 hour while they are fasting. Then, each individual will ingest a 
500 Kcal mixed solid-liquid meal consisting of scrambled egg, bread, pudding, and milk at each 
test meal (Appendix 1). Pressure activity will be recorded after each test meal (10). The 
participant will be seated at a 45 degree angle during this test.  
 
The gastroduodenal tube will remain in place and the gastrointestinal manometry test will be 
performed again 4 hours later at the lunch meal. The lunch GDM measurements will be 
performed while sham or active TENS treatment is taking place. 
 
Figure 4 shows the postprandial gastric motility 
following ingestion of a solid-liquid meal. Note the 
increased frequency of distal antral phasic 
contractions and coordination with pyloric and 
duodenal motility.  Reproduced from ref. 11.  
 
Figure 5 shows a correlation between distal antral 
contraction amplitude and rate of gastric 
emptying (12). 
 
 
 
 
Analysis of manometric recordings  
Antrum: Phasic pressure activity in the distal antrum recorded on the manometric tracing is 
quantified manually. The most distal antral site will be identified as a site recording up to three 
waves per minute, which is (a) just  proximal (1cm) to a  site recording duodenal-type wave or 

Camilleri et al. - 8 - 
 
(b) just proximal to a site exhibiting a mixture of antral-type and duodenal-type waves associated 
with baseline elevation (pyloric-type activity). For each sequential 15-minute period and for the 
1-hour postcibal period, a motility index (MI) will be calculated using the formula: MI = log 
(sum of amplitude x number of contractions + 1). The average 15-minute antral MI will be 
calculated, as previous studies showed that the cumulated slope of antral motility indices is linear 
(13). 
 
Statistical Analysis 
 
Sample size assessment - The standard deviation used for the sample size calculations was 
calculated from the observed value of distal antral activity in healthy volunteers in the absence of 
any treatment: 14.3±0.66 (SD) (10,13). Comparison of 8 Participants in the active vs. sham 
treatment arms will have sufficient power to detect a difference between the 2 groups (Unpaired 
t-test; Parallel group design) of distal antral MI of 0.995units or 7.0% relative to controls (10,13). 
It is to be noted that the antral MI measurement is on a logarithmic scale and, therefore, a 10% 
reduction in antral motility index is clinically relevant since it is associated with reduction in 
gastric emptying rate. 
 
Response 
Mean 
SD 
Predicted detectable effect size (%(absolute #)),   
n=8 per group unpaired analysis  
Postprandial distal antral motility index 
14.3 
0.66 
7.0% (0.995 MI units)  
Data obtained from ref. 10; predicted detectable effect size is shown with 80% power, α=0.05.  
 
Statistical Methods 
 
It is anticipated that the primary endpoint (the logarithmically transformed antral MI) will be 
normally distributed. We shall use an unpaired student’s t-test to compare the antral MI in the 
sham versus active treatment groups. 
 
An interim analysis will be performed for “futility” assessment after the first 8 participants.  In 
such an analysis, we would have 4 patients per group, assessed in unpaired t test based on 
parallel group design. Using the same SD of 0.66, a comparison of 4 patients per group would 
have sufficient power to detect a significant difference in antral motility index of 1.572 (11 %) .  
If the interim analysis shows that the antral MI difference between the 2 groups is <0.75 (~5%), 
we would consider whether it would be futile to continue the study and completing 16 
participants.  On the other hand, if the difference in mean antral MI is >0.75 in the two groups, 
we would complete the study.  Since this interim analysis is conducted for “futility” rather than 
for efficacy, we will not correct the α statistic from 0.05 (e.g. to 0.025) on completion of the pre-
specified sample of 16 subjects.  
 
Anticipated Results and Significance  
 
We anticipate a lower antral motility index with active T6 dermatomal TENS treatment 
compared to sham treatment. This physiological study will provide information about the 
potential effect of T6 dermatomal stimulation on gastroduodenal motility, that could play a role 
in inducing other effects currently under investigation (appetite reduction, gastric emptying etc). 
 

Camilleri et al. - 9 - 
 
Device Safety: Designation of Non-Significant Risk 
 
Based on the FDA guidance on Significant Risk and Nonsignificant Risk Medical Device 
Studies (14), 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.  
 
Appendix 1 
 
Test meal nutritional information: 
 
Item 
Amount 
Unit 
Weight (g) 
Kcal 
g Carbohydrate 
g Protein 
g Fat 
Egg, Extra Large 
2 
Item 
112 
160 
2 
14 
10 
Bread, Whole 
Wheat 
1 
Slice 
36 
100 
17 
5 
2 
Jell-O® Vanilla 
Pudding 
1 
Item 
110 
110 
23 
1 
1.5 
Milk- 2% 
1 
Item 
240 
130 
12 
8 
5 
TOTAL 
N/A 
N/A 
498 
500 
54 
28 
18.5 
 
 
 

Camilleri et al. - 10 - 
 
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