Facilitated Release of Endogenous Enterokines: An Ambulatory Prospective Randomized Controlled Trial
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Sponsor: University of Southern California

Ver 3.11.14 
 
 
DRAFT PROTOCOL​ NUMBER: Pending
 
 
TITLE: FREE TO GO 
S​TUDY PHASE​: CLINICAL STUDY
 
STUDY GROUPS: WITH AND WITHOUT JEJUNAL NUTRIENT ADMINISTRATION 
IND OR IDE #: Not Applicable 
 
PRINCIPAL INVESTIGATOR: 
Elizabeth Beale MD MRCP (UK) MMED MS (Clin Invest) 
Assistant Professor in Clinical Medicine 
Division of Endocrinology and Diabetes KSOM USC 
beale@usc.edu 
 
CO-INVESTIGATORS:  
 
WeiAn Lee, DO 
Assistant Professor in Clinical Medicine 
Division of Endocrinology and Diabetes KSOM USC 
weilee@usc.edu 
 
Peter Crookes, MD 
Professor of Surgery 
Department of Surgery KSOM USC 
Peter.Crookes@med.usc.edu 
 
James Buxbaum, MD 
Assistant Professor of Clinical Medicine 
Division of GI and Liver Diseases ​KSOM USC 
jbuxbaum@usc.edu 
 
Hongsheng Tong DDS PhD 
Clinical Assistant Professor 
Advanced Orthodontics 
Hermon Ostrow School of Dentistry of USC 
drhstong@gmail.com 
 
Philong Pham BS MS DDS 
Resident 
Advanced Orthodontics 
Hermon Ostrow School of Dentistry of USC 
philongpham@gmail.com 
 
 
COLLABORATOR 
 
Viorica Ionut, MD PhD 
Assistant Professor 
Biomedical Sciences 
Diabetes and Obesity Research Institute Cedars Sinai Medical Center 
Viorica.Ionut@cshs.org 
 
 
SPONSOR: USC 
SUBJECTS/L​OCATONS​: ROYBAL DIABETES MANAGEMENT CLINIC 
FUNDING SOURCE: CORPAK Medsystems, Wallace H. Coulter Foundation  
 
AMENDMENTS/REVISIONS: None  
 
 
 
 
1 
 

Ver 3.11.14 
 
 
ABSTRACT  
Background The overall objective of our work is to develop therapy for obesity and diabetes that is as effective as gastric
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
bypass surgery but without the cost and safety concerns. Gastric bypass leads to rapid, sustained diabetes remission in the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
majority of patients who undergo this procedure and is also highly effective therapy for obesity. However currently <1% of
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
medically-eligible patients undergo this or other bariatric operations due to cost and safety concerns. Our approach is based
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
on data suggesting that the benefit of gastric bypass is largely due to anatomical rearrangement of the intestine which leads
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
to accelerated delivery of nutrients to the jejunum. This rerouting of nutrients stimulates the release of multiple neural,
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
hormonal and enterokine responses that are associated with appetite suppression and improved glucose control.  
In this proof-of-concept pilot proposal we are asking the question: can repeated rapid delivery of a mixed meal directly to
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
the jejunum promote weight loss and blood glucose control?  
Hypothesis: Administration of intermittent mixed meal bolus daily via jejunal tube over a 2 week period leads to weight
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
loss and improved glycemic control that is associated with reduced food intake and is sustained for 2 weeks of follow up. 
Specific Aims:​ In obese, ambulatory, adult patients with type 2 diabetes receiving mixed meal (intervention) or electrolyte 
solution (control) boluses daily via jejunal tube for 14 days, with 14 days follow up and with other oral nutrition permitted 
throughout, to compare the following:  
Primary aim: weight change immediately following the intervention period between the study groups 
Secondary aims to compare the following within and between groups: From Day 0 to Day 14: caloric intake (as determined 
by consumption of provided food), From Day 0 to Day 14: weight change (within group),From Day 0 to Day 28: weight 
change From Day 0 to Day 14 and also from Day 0 to Day 28: waist and hip measurement, hormones and biochemical 
measures, physical activity , body composition , symptoms, medication use, average self-monitored blood glucose level 
Study Design​: Prospective, randomized 2 group pilot study: 14 days with tube, 14 days follow up. The feeding tube will be anchored
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
intraorally so that it is not apparent to observers when not in use. 
Major Inclusion Criteria​: 18-70 years of age, BMI ​>​30kg/m​2​, type 2 diabetes on oral antidiabetic agents only, A1C<9%. 
Major Exclusion Criteria​: Use of incretin-based therapy, insulin, contraindication to tube (prior upper gastrointestinal bleed 
or history of easy bleeding, altered foregut anatomy due to obstruction or surgery), known cardiovascular disease other than 
controlled hypertension, pregnancy, no acceptable contraception, known​ prior abdominal problems that could prevent the 
spontaneous passage of a 10 French jejunal tube if it were to dislodge distally. 
Withdrawal Criteria​: any request by subject, specified clinically significant complications secondary to the intervention. 
Study Site​: Edward R. Roybal Comprehensive Health Center (CHC) and ambulatory. 
Method​: Approximately day -14: In preparation for placement of intra-orally anchored jejunal tube dental spacers will be
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
placed by study orthodontist. Approximately day -7: Dental anchor placed by orthodontist. 
Day 0: Subject presents fasting to the CHC. Blood pressure, heart rate, weight, height and waist circumference and body
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
composition on InBody520 BioSpace will be recorded. FitBit® activity monitor placed. Subjects will have a jejunal feeding
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
tube placed by the investigator using a CORPAK EAS™ and will then be randomized to the control or intervention group.  
Day 0-Day 14: Subjects will take a mixed meal or electrolyte solution at a prescribed rate and interval and will be requested
 
 
 
 
 
  
 
 
 
 
   
 
 
 
 
 
 
 
 
to eat ad lib only from provided meals of known caloric amount or from a list of low calorie items. Subjects will maintain a
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
log of all food intake, temperature at least daily, tube position and symptoms and blood glucose 4 times a day.  
Day 7: The subject will return to the CHC for review for continuation in the study, of their log and caloric intake and for
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
adjustment of medication if necessary and activity monitor download. 
Day14: Day 0 measures will be repeated at the CHC and the tube removed. All uneaten food will be returned for caloric
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
intake determination, activity monitor download. 
Day 15-Day 28: The subject will maintain a medication and blood glucose log for 14 days after the removal of the tube.  
Day 28: Exit outcome measures similar to those at Day 0. 
​Safety: The subjects will be monitored for fever, sore throat, displacement of the tube, gastrointestinal upset, vital signs,
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
biochemical measures and weight change, and if pre-specified criteria are met or in the clinical judgment of the PI it is not
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
   
 
appropriate to continue, will be withdrawn from the study.  
Outcome Measures:​ weight change, caloric intake, waist and hip measurement, hormones and biochemical measures, 
physical activity , body composition , select symptoms, medication use, average self-monitored blood glucose level 
Reimbursement:​ Subjects will receive standardized meals of known caloric amount for 2 weeks and up to $300 cash. 
Statistics ​This is a pilot study and sample size estimates are not appropriate. However based on studies of dietary restriction
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
with a 1250 kcal diet for 1 week we anticipate identifying a significantly greater weight loss in the intervention arm with a
  
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
  
sample size of 10 subjects/group. Fifteen subjects/group will be enrolled to allow for drop-outs.  
Analysis: Primary analysis will be to compare change from baseline in outcome measures between the 2 groups using
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
paired t-test. SC CTSI Biostatistics Department has aided in the study design. 
2 
 

Ver 3.11.14 
 
Human Subjects​: This is a moderate risk study using a variant of a standard ambulatory intervention. Potential benefit in
 
 
   
 
 
 
  
 
  
 
 
 
 
 
 
identifying a safe, simple weight loss intervention justifies risks. 
 
 
TABLE OF CONTENTS 
 
 
SCHEMA, ​SYNOPSIS, OR STUDY SUMMARY
 
PAGE 
 
1.0
BACKGROUND AND HYPOTHESES 
__4___ 
 
2.0
OBJECTIVES ​AND PURPOSE
__8___ 
 
3.0
STUDY DESIGN 
__8___ 
 
4.0
DRUG/​DEVICE​ INFORMATION
__10___ 
 
5.0 
SELECTION ​AND WITHDRAWAL OF SUBJECTS
__13___ 
 
6.0
DESCRIPTIVE FACTORS/STRATIFICATION/RANDOMIZATION SCHEME
__14__ 
 
7.0 
STUDY ​AGENT ADMINISTRATION OR INTERVENTION​ AND TOXICITY​                    ​  __14__ 
              ​MANAGEMENT PLAN
 
8.0
A​SSESSMENT OF EFFICACY AND SAFETY
__14__
 
9.0
CLINICAL AND LABORATORY EVALUATIONS
__20___ 
 
10.0
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS
__21___  
 
11.0
SPECIAL INSTRUCTIONS
__21___ 
 
12.0
DATA COLLECTION AND MONITORING
__21___ 
 
13.0
STATISTICAL CONSIDERATIONS 
__21___ 
 
14.0
REGISTRATION GUIDELINES 
__22___ 
 
15.0
BIOHAZARD CONTAINMENT
__22___ 
 
16.0
ETHICAL AND REGULATORY CONSIDERATIONS
__22___ 
 
17.0
REFERENCES
               __30___ 
 
 
 
 
 Appendices 
A.
FREE TO GO Nutrition: Essential and Optional and Study Supplies                                                 __23__ 
B.
FREE TO GO Study Instructions                                                                                                       __ 25__ 
C.
FREE TO GO Daily Log                                                                                                                   ___27__ 
1.0
 
3 
 

Ver 3.11.14 
 
BACKGROUND​ AND HYPOTHESES 
 
More than two-thirds (69%) of US adults are overweight, with more than 36% obese and more than 6% having morbid
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
obesity. [​1​] ​Over 80% of type 2 diabetes is attributed to excess weight and obesity,[​2​] ​but safe, effective, low-cost treatment
 
 
 
 
 
  
  
  
 
 
 
 
 
 
 
 
 
is not available. ​Failure to control obesity underlies the increasing cost of diabetes care in the US which rose by 41%
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
from 2007 to $245 billion in 2012.[​3​] Most of the cost of care (62%) is provided by government insurance.[​3​]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmaceutical therapy has proven disappointing for management of obesity: it is relatively ineffective, associated with
 
 
 
 
 
 
 
 
   
 
 
 
 
severe side-effects and expensive.  
 
Various bariatric surgical procedures are highly effective at inducing weight loss and lead to drug-free remission in 40-90%
 
 
 
 
 
 
  
 
 
 
 
  
 
  
 
of patients. ​[​4​, ​5​] ​(Fig 1). However a recent US study ​[​6​] of 29,820 Blue Shield plan members who underwent bariatric
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
surgery (at a cost of over $28,000/procedure) and a comparison group of persons not undergoing surgery but with diagnoses
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
closely associated with obesity found ​no reduction in overall health care costs with surgery during a 6-year follow-up
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
period. This was due to high inpatient costs that were not offset by a reduction in office visits and prescription medications.
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
Bariatric surgery is not available to the vast majority of the world’s population who might benefit from it, including low
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
income individuals, the young, the elderly and those with early or mild disease. D​ue to concerns about short and long term
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
risk, surgery is generally limited to adults with complicated obesity and a BMI of ​>​35kg/m2, or severe obesity with a BMI
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
of ​>​40kg/m​2​.[​7​] ​Furthermore many individuals elect not to undergo bariatric surgery for a variety of reasons that include
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
concerns about the risks, unwillingness to undergo an irreversible procedure and the belief that their obesity does not justify
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
the intervention.  
 
There is thus an unmet clinical need for a safe, low-cost alternative to bariatric surgery.  
 
 
 
Background Physiology  
 
Sustained weight loss is seen in the majority of patients undergoing gastric bypass surgery (GB). The amount and
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
sustainability of the weight loss is far superior to that achieved by current pharmacological and lifestyle treatments.[​8​, ​9​]
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Contrary to earlier beliefs, mechanical restriction of food intake and malabsorption are now not considered to be major
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
mediators of benefit. It is now widely accepted that following GB there is rapid increase in satiety that is likely mediated by
 
 
   
 
 
 
 
 
 
  
 
  
 
  
 
 
 
4 
 

Ver 3.11.14 
 
several different mechanisms, with neurohormonal signaling and enterokines playing a central role.[​10​] ​Over 100
 
 
 
 
 
 
 
 
  
 
 
 
 
enterokines (i.e. enteric hormones and other factors such as bile acids with systemic metabolic effects) help regulate energy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
balance. The enterokine GLP-1 is considered to be a major contributor to benefit. It is normally secreted by intestinal
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
L-cells in response to nutrient ingestion, and has multiple appetite suppressing and glucose-lowering actions including
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
promotion of insulin secretion, inhibition of glucagon, slowing of gastric emptying, portal-sensor/vagally mediated central
 
 
 
 
 
 
 
 
 
 
 
 
 
 
actions, and in animals at least, promotion of pancreatic-beta cell regeneration. In post-operative GB patients, the GLP-1
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
response to oral glucose or a standard meal increases 4-6-fold.[​11​] ​A second hormone of particular interest is PYY which is
 
 
 
 
  
 
 
 
  
 
 
 
 
  
 
  
co-secreted with GLP-1 also in response to nutrients, promotes satiety and is markedly increased following GB.[​12​]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Changes occur rapidly: Dirksen et al reported that in a post-GB patient with type 2 diabetes glucose tolerance improved or
 
 
 
   
 
 
  
 
 
 
  
 
 
 
 
 
worsened on successive days by feeding the patient by mouth or via a gastrostomy tube respectively[​13​] Falken et al
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
showed significant changes in enterokines, glucose tolerance and satiety 3 days post GB.[​14​]  
 
Studies in patients undergoing GB have identified a distinctive
 
 
 
 
 
 
  
 
synergistic
cascade
of
appetite-suppressing
and
 
 
 
 
 
glucose-lowering responses triggered by delivery of food
 
 
 
 
 
 
 
directly to the jejunum. (Fig 2).[​15​] Rapid changes occur in
 
 
 
 
 
 
 
 
 
 
numerous gut hormones (including a rise in intact and total
 
 
 
  
 
 
 
 
 
GLP-1,
PYY,
CCK,
C-peptide
and
insulin),
gut-brain
 
 
 
 
 
 
 
signaling via the vagus nerve and bile acid entero-hepatic
 
 
 
 
 
 
 
 
 
circulation. These rapid changes mediate multiple short and
 
 
 
 
 
 
 
 
medium term effects that suppress appetite and control
 
 
 
 
 
 
 
 
glucose. Unlike other weight loss strategies (e.g. diet, exercise
 
 
 
 
 
 
 
 
 
and gastric banding) GB is associated with a “fed” rather than
 
 
 
  
 
  
 
 
 
a “non-fed” neurohormonal response that is considered to
 
 
 
 
 
 
 
 
underlie the characteristic increase in satiety and activity seen
 
 
 
 
 
 
 
 
 
post GB and the ability to sustain weight loss.[​8-10​, ​16​] 
 
A simple nasojejunal feeding tube (NJT) is similar in many
 
 
 
 
 
 
 
 
 
 
ways to gastric bypass as it also leads to nutrient bypass of
 
 
 
 
   
 
 
 
 
 
 
the foregut and delivery directly to the jejunum. (Fig 3)  
 
In this study we propose evaluating proof of
 
 
 
 
 
 
 
 
concept that rapid delivery of nutrients directly to
 
 
 
 
 
 
 
 
the jejunum promotes weight loss and glucose
 
 
 
 
 
 
 
control
that is superior to that seen when a
 
 
 
 
 
 
 
 
 
non-nutrient liquid is delivered to the jejunum. 
 
Proof of concept would justify the development of
 
 
 
 
 
 
 
 
methods to allow direct delivery of bolus nutrient to
 
 
 
 
 
 
 
 
 
the jejunum that could be an alternative, lower cost, reversible alternative to GB surgery. 
 
Preliminary Data  
In late 2012 we initiated pioneering human proof-of-concept studies of our hypothesis that delivery of nutrients directly
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
to the jejunum with standard NJT simulates the actions of GB. To our knowledge we are the first investigators to use the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
newly approved CORTRAK 2 Enteral Access System (EAS™) to rapidly and safely place jejunal tubes using
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 
 

Ver 3.11.14 
 
electromagnetic guidance in non-sedated outpatient volunteers. Key preliminary findings support both our technical
 
 
 
 
 
 
 
 
 
 
 
 
 
approach and hypothesis.  
 
So far we have: 
-Successfully placed 23 of 25 nasojejunal tubes attempted in an average time of about 15 minutes (one tube could not be
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
passed through the nasopharynx, 1 through the pylorus). 
-Conducted 23 paired 3 hour 11 sample meal tolerance
 
 
  
 
 
 
 
 
tests in obese adult subjects with type 2 diabetes. Each
 
 
 
 
 
 
  
 
 
subject underwent a nasojejunal (NJ) and a paired oral
 
  
 
 
  
 
 
(PO) test. Some data is shown in Figure 4. 
 
We
identified
a
significant
increase
in
GLP-1,
 
 
 
 
 
 
 
C-peptide, insulin and PYY and a trend towards a lower
 
 
 
 
  
 
  
 
glucose in 7 paired tests with a dose of 120mls Ensure
 
  
 
 
  
 
 
 
 
Nutrition Shake over 15mins (8kcal/min) and a much
 
 
 
 
 
  
 
greater response in 3 individuals who underwent paired
 
 
  
 
 
 
 
tests of 237mls Ensure Nutrition Shake over 30mins
 
 
 
 
 
 
 
 
(also 8kcal/min). A single individual who underwent a
 
 
 
 
 
 
  
paired test of 237mls over 15minutes (16kcal/min) had
 
 
 
 
 
 
 
 
the greatest GLP-1 response but this dose was poorly
 
 
 
 
 
 
 
 
 
tolerated and not repeated. All tubes were placed just
 
 
 
 
 
 
 
 
 
distal to the ligament of Treitz at the entrance to the
 
 
 
 
 
 
 
 
 
 
 
jejunum. (Unpublished: pending completion of assays). 
 
Similar Work by Others 
Recent work published in 2013 by Breitman et al, [​17​]
 
 
 
 
 
 
   
 
 
Salinari et al,
​[​18​] and Marathe et al [​19​, ​20​] offer
 
 
   
 
 
     
 
 
 
support of our concept. In these studies obese and
 
 
 
 
 
 
 
 
 
non-obese
and
diabetic
and
non-diabetic
subjects
 
 
 
 
 
 
demonstrated significant increase in incretin hormone
 
 
 
 
 
 
responses with jejunal feeding in studies of 2 and 3
 
 
 
 
 
 
   
   
days
duration.
Of
note,
Marathe
et
al
​[​20​]
 
 
 
 
 
 
 
 
demonstrated
a
rate
dependent
effect
of
incretin
 
 
 
 
 
 
 
stimulation with a greater effect observed at 4kcal/min vs. 2kcal/min. Corroborating data is also provided by Kaushik et
 
   
 
 
   
 
 
 
 
   
 
 
 
   
al[​21​] who described release of satiating hormones with jejunal feeding during treatment for pancreatitis​. ​Similarly Welch
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
et al[​22​] reported a reduction in total caloric intake in normal volunteers offered an oral meal during a low calorie jejunal
 
 
   
   
 
 
   
 
 
 
 
 
 
   
 
 
 
infusion of lipid but not saline. We consider these preliminary findings to strongly justify further objective evaluation and
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
refinement of our approach.  
 
Tube and Non-Nutrient Liquid May Alter Oral Food Intake 
Rolls and Roe[​23​] reported in a study of 54 lean and obese women that ​the volume of liquid food infused 
intragastrically affected subsequent energy intake in both lean and obese women. There was a mean decrease 
in energy intake of a subsequent meal of 13% after a 400-ml preload compared with an iso-energetic 200-ml 
preload (P=.013). ​For this reason a controlled study should include a tube and non-nutrient liquid administration.  
 
How jejunal feeding in this study differs from that used for standard jejunal feeding 
Jejunal feeding is used in ambulatory and hospitalized patients to provide nutrition when this cannot be taken by the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
standard gastric route, or as a choice by the physician to minimize reflux associated with gastric feeding, usually in
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
semiconscious or critically ill patients. In such cases it is well accepted standard care
that the tube feeds should be
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
started slowly and often given at a slow rate around the clock in order to achieve target caloric and nutritional intake.[​24​]
 
 
 
 
     
 
 
 
 
   
   
 
 
 
 
 
 
It is frequently reported that jejunal feeds are “poorly tolerated”. Interpretation of the effect of jejunal feeds on weight is
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
complicated by the underlying need for the jejunal feeds which includes conditions such as pancreatic cancer, pancreatitis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
and gastroparesis. A key difference in the approach proposed in this study is the administration of bolus feeds at a far
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
     
 
higher rate than normally given during standard feeding protocol with the express intention of inducing a satiated state at
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
   
low caloric intake.  
 
6 
 

Ver 3.11.14 
 
How Jejunal Feeding differs from the ketogenic enteric nutrition or “Bride Diet “and other low calorie diets 
Low and very low calorie diets, if sustained, lead to weight loss. This is often associated with a lack of hunger during the
 
 
 
 
 
   
 
   
 
 
   
 
 
   
 
 
 
 
 
low calorie intake period that may be due to the induction of ketosis and ghrelin suppression.[​25​] In general weight loss
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
following caloric restriction is not sustained and short-term metabolic gains dissipate.[​16​] This has been attributed to the
 
 
   
 
 
 
 
 
 
 
 
 
 
   
 
body’s attempt to regain its previous weight with resumption of a non-restricted intake. The superior sustained weight
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
loss seen with GB may be due to neurohormonal signaling of an “overfed” state during the low calorie phase leading to
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
defense of the lower weight once the intervention is withdrawn. We aim to simulate this “fed” response with jejunal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
feeding.  
With respect to the ketogenic enteric nutrition diet, this 200-260kcal/day diet induces ketosis during a continuous
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
administration of primarily protein into the stomach. This strategy is reported to minimize protein catabolism during the
 
 
 
 
 
 
 
 
   
   
 
 
 
 
 
diet. The intragastric continuous infusion is distinct from the jejunal bolus approach we propose. The diet is of interest to
 
 
 
 
   
 
 
 
 
 
 
 
 
 
   
 
   
us however as it demonstrates the safety and acceptability of ambulatory tube use for weight loss. A report by Cappello
 
 
   
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
et al described its use in over 19,000 individuals in Italy.[​26​]  
 
How much weight loss can be expected with a diet equivalent to gastric bypass diet for 14 days (see table 2) 
Recent data from Lingvay et al[​27​] and Jackness et al [​28​] suggest that individuals taking a typical post GB very low
 
 
 
 
 
 
 
     
 
 
 
 
   
 
 
 
 
 
calorie diet of 250-500kcal/day lose about 3% of body weight or 3-4kg in one week. ​An average deficit of
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
500 kcal/day should result in an initial weight loss of approximately 0.5 kg/week (1 lb/week).[​29​] ​Weight loss is greater in
 
 
 
 
 
 
 
 
 
 
 
  
  
men and younger individuals and is influenced by genetic factors.[​29​] It is also greater post bariatric surgery in those with a
 
 
 
 
  
 
 
 
   
 
 
 
 
  
 
  
higher pre-operative weight. However, after three to six months of weight loss, energy expenditure adaptations occur which
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
slow the bodyweight response to a given change in energy intake, thereby diminishing ongoing weight loss.[​30​] [​31​] 
 
Outcomes with  Very Low Calorie Diet (VLCD)​.(see table 2) Currently thousands of individuals undergo prolonged very 
low calorie diets following gastric bypass surgery without problem and these are used alone too. Standard of care requires 
ensuring subjects take appropriate amounts of protein daily (equivalent to 1g/kg of lean body weight). 
 
Table 2 Calorie Restricted Diets: weight loss, safety and tolerability 
Ref 
Population 
Intervention 
Duration 
Weight loss 
Safety
and
 
 
Tolerability 
Bray[​29​] 
In general 
Calorie
deficit
of
 
 
 
500 kcal/ day  
various 
0.5 kg(1lb)/week  
Tolerable
but
 
 
poorly sustained 
Lingvay[​27​] 
N=10  
Age: 53.2 years  
(95% CI, 48.0–58.4);  
BMI: 51.2 kg/m​2  
(46.1–56.4)  
Diabetes duration: 7.4 years  
(4.8–10.0)  
HbA1c: 8.52% (7.08–9.96%). 
Typical peri-bariatric 
surgery diet  
250kcal/day for 1 week  
With and without RYGB 
Inpatient stay  
Separated by​>​6 weeks  
Patients were own 
controls.  
7 days 
 
Diet only: 
5%  
-7.26 kg (6.41-8.11) 
( start: 141kg) 
Surgery + diet: 
3% 
-3.95kg (1.7-6.2)  
(start: 131kg)  
No report of any
 
 
 
 
adverse
events
 
 
related to diet or
 
 
 
 
surgery 
Jackness[​28​] 
RYGB with diabetes: N=11 
Matched controls: N=14 
BMI of 41.2 kg/m2.  
Diabetes duration: 5.7 +/-0.9 
years  
(range, 0.5 - 15)  
HbA1c 8.4 +/-0.3%;  
 (Range, 6.2 – 11.1%). 
500 kcal/day  
 
macronutrients similar to 
Post RYGB.  
 
21 days 
Diet Controls:: 
-8.6kg 
(Start:  
Wt: 114.2+/-6.6kg;  
BMI: 39,2+/1 kg/m​2​) 
Surgery Group: 
-9.1kg  
(Start  
Wt: 121.4+/-6.7kg 
BMI: 43.2 + 2.3 
kg/m​2​) 
Overall:ie 7.6 +/-0.4% 
over 3 weeks 
2.5%/week 
? higher in 1​st​ week 
No report of any
 
 
 
 
adverse events  
Cappello[​26​] 
19,036 patients  
age 44.3 ± 13 
M:F = 2:5)  
BMI 36.5 ± 7.1 
22% diabetes 
200 to 260kcal/d 
50–65 g of proteins plus 
vitamins and 
electrolytes/d. 
2.5 
10-day 
cycles  
 
25 days 
10.2 ± 7.0 kg of body 
weight,  
5.8 ± 5.5 kg fat mass 
and 2.2 ± 3.3 kg of 
lean body mass. 
No significant 
adverse effects 
except asthenia and 
constipation - easily 
controlled  
7 
 

Ver 3.11.14 
 
Enteral nutrition through 
a fine nasogastric tube.  
 
Est. 3kg/week  
Jazet[​32​] 
Eighteen insulin-treated obese 
type 2 diabetic patients 
BMI 37.6 +/-1.1 
Insulin Units/day: 137+/-22 
Cessation of all 
glucose-lowering medication.  
450 kCal/day 
VLCD(Modifast 50 g 
protein, 
50–60 g carbohydrates 
and7 g lipids daily)  
30days  
-11.7 +/-0.7 kg  
-4.9+/-1.0kg/m​2 
 
No significant 
adverse effects 
 
 
 
HYPOTHESIS: Administration of intermittent mixed meal bolus daily via jejunal tube over a 2 week period leads to weight
 
 
 
 
 
 
 
 
 
 
 
   
 
 
  
 
loss and improved glycemic control that is associated with reduced food intake and is sustained for 2 weeks of follow up. 
2.0
OBJECTIVES AND PURPOSE 
Specific Aims:​ In obese, ambulatory, adult patients with type 2 diabetes receiving mixed meal (intervention) or electrolyte 
solution (control) boluses daily via jejunal tube for 14 days, with 14 days follow up and with other oral nutrition permitted 
throughout, to compare the following:  
Primary aim: weight change immediately following the intervention period between the study groups 
Secondary aims: to compare the following within and between groups:  
a.
From Day 0 to Day 14: caloric intake (as determined by consumption of provided food)  
b.
From Day 0 to Day 14: weight change (within group) 
c.
From Day 0 to Day 28: weight change  
d.
From Day 0 to Day 14 and also from Day 0 to Day 28: waist and hip measurement, hormones and 
biochemical measures, physical activity , body composition , select symptoms, medication use, average 
self-monitored blood glucose level 
 
3.0
STUDY DESIGN 
Study Design: Prospective, randomized, 2 group, pilot study: 14 days with jejunal tube, 14 days follow up. Subjects will
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
receive intermittent bolus feeding into the jejunum with either mixed meal or non-nutrient liquid. The study will
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
otherwise be the same. In this study the jejunal tube will be secured intraorally on an orthodontic molar band to avoid
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
uncomfortable and conspicuous nasopharyngeal placement. 
Recruitment​ Information sessions and study materials will be provided to clinic physicians who may refer subjects from within the 
LA County Healthcare Network to explain the study protocol. IRB approved flyers will be placed in approved recruitment 
areas. In addition clinic providers will request permission from patients to forward their names and contact information to 
the study recruiter if they meet eligibility criteria. If the patient agrees to have their name forwarded to the study team then 
this will be documented in the permanent medical record. The study recruiter will contact potential subjects and describe 
details of the study using an IRB script. If the potential subject remains interested in participating the PI and CoI will 
follow-up with further discussion and review of the protocol with the potential subject. Participants will be provided with 
diabetic education describing the signs and symptoms of hyperglycemia and hypoglycemia and their management. This will 
be provided by the study doctor when the protocol is discussed with the potential subject and will be reviewed at each 
subsequent visit. 
 ​Approved illustrations of the proposed intervention as well as the informed consent will be provided to the potential 
subject and they will be allowed to review this in their own time. All questions will be addressed by the PI and CoI 
before consent is signed. 
Study Site:​ Edward R. Roybal Comprehensive Health Center. 
 
Method​:  
 
Approximately Day -14: After ​Informed consent has been taken and ​dentition has been assessed, the study orthodontist
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
will place dental spacers (small rubber strips) around an upper molar.  
 
Approximately Day -7: Approximately 1 week (minimum 2 days) later a stainless steel orthodontic molar band modified to
 
 
 
  
 
  
 
  
 
 
 
 
 
  
anchor the jejunal tube will be cemented to the selected molar. This will also be done in the Dental Clinic at Edward R.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
Roybal CHC without sedation or anesthesia. Two visits may be required for this step: 1 to measure for the dental band and
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
the second to place it.  
 
8 
 

Ver 3.11.14 
 
There may be as little as 2 days or as long as several weeks from the time the spacers are placed to the time the tube is
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
placed depending on subject and study team member availability and technical aspects of the band and tube placement (i.e.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
how long it takes for the spacers to separate the teeth adequately, whether the subject requires 1 or 2 visits to fit the molar
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
 
 
band and whether the subject has the tube placed the same day as the molar band). 
 
Day 0: The ​subject will be seen at the CHC in the fasted state. ​All women between 18 and 50 years of age who have not
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
undergone hysterectomy or tubal ligation will undergo a urine pregnancy test. If the test is positive then they will not be
 
 
 
 
 
 
  
 
 
  
 
  
 
 
 
 
 
 
eligible to participate. ​Baseline vital signs, weight, height and waist and hip circumference will be recorded and baseline
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
labs drawn. ​Body composition will be measured by the Biospace InBody 520 device (Biospace, Cerritos CA 90703
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
http://www.biospaceamerica.com/​)​. This device measures body composition non-invasively as the subject stands on a
 
 
 
 
 
 
 
 
 
 
 
  
scale-like device while grasping two handles – one in each hand.
The device works by sending a very low voltage
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
electrical signal through the body to determine water content, body fat percentage, and lean mass. The machine will be
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
kept in the basement of the CHC. The ​FitBit Monitor is placed on the subject’s wrist or clothing and will record activity
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
for up to 2 weeks at a time without need for any adjustment be the wearer. 
 
Body weight will be measured in the morning on a calibrated scale with the subject wearing light clothing. ​Waist 
circumference will be measured by wrapping a flexible measuring tape around the narrowest point of the 
midsection. The tape will be kept parallel to the floor. Hip circumference will be measured by wrapping a flexible 
tape around the hips at the widest diameter of the buttocks. The tape will be kept parallel to the floor. The 
waist-to-hip ratio will be determined by taking the waist circumference and dividing by the hip circumference. 
 
Subjects will have a 10 French 140cm tube placed using a CORPAK EAS™by the PI or CoI following standard
 
 
   
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
technique and will be randomized to the intervention or control group. (See Appendix A: Tube Placement Using EAS™).
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
It usually takes about 20 minutes to place the tube but can take as little as 5 minutes or up to an hour. If the tube cannot
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
   
 
   
 
 
 
be positioned in the intestine within 1 hour it may be allowed to move into position naturally overnight. In this case the
 
 
 
 
 
   
   
 
 
 
 
 
 
 
 
 
 
 
 
 
participant would come back a day or 2 later to check that the tube has reached the correct position. In this case the tube
 
 
 
   
 
   
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
feeds would only start when the tube is shown to be in the correct position. 
 
Subjects will be provided with detailed instructions and logs for the following: (See Appendix B: Subject Packet).   
1. Bolus nutrient administration and flushing of tube 
2. Eating: to eat ad lib from provided meals of known caloric amount 
3. Daily self-monitoring and tube care  
4. 24 hour contact information 
5. Need to monitor blood glucose prior to tube bolus 
6. Use of FitBit activity monitor and daily activity 
Prior to leaving, the subject will self-administer the first tube bolus and demonstrate by verbal response understanding of
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
requirements for the study. 
 
▪
Day 0-Day 14: (see Table 3) 
▪
Intervention subjects will take mixed meal via jejunal tube at 10mls/min to satiety or to a maximum volume of 
200mls 4 times a day. They will also take 200mls electrolyte solution 4 times daily orally.  
▪
Control subjects will take electrolyte solution via jejunal tube at 10mls/min to satiety or to a maximum volume of 
200mls 4 times a day. They will also take 200mls mixed meal solution 4 times daily orally. 
▪
If for any reason the tube feed cannot be administered the remainder should be taken orally to ensure 
recommended daily intake of major nutrients and fluid is achieved. 
▪
In addition all subjects will take the following daily:  2 10meq potassium chloride tablets, 2 600mg calcium tablets 
and 1 multivitamin tablet daily and 1/2tsp salt. 
▪
In addition all subjects will be requested to eat ad lib from provided meals of known caloric amount.  
▪
All subjects may also eat ad lib from very low or calorie “free” foods and drinks throughout the study from a 
provided list. 
▪
 Subjects will maintain a log of all food intake will check their daily temperature, tube position and symptoms and 
will contact the study team for specified symptoms or if they have any concerns they would like addressed.  
▪
As subjects adhering to very low-calorie diets usually have a fall in blood pressure, especially during the first week 
antihypertensive drugs will be discontinued unless moderate to severe hypertension is present.[​33​] 
9 
 

Ver 3.11.14 
 
▪
Subjects will be requested to be as physically active as they like. Thus they are at liberty to increase, decrease or 
maintain their usual activity level. 
▪
 Similarly as most diabetic patients eating very low-calorie diets have marked improvement in hyperglycemia with 
blood glucose concentrations falling within the first one to two weeks oral hypoglycemic drugs will be 
discontinued for the first week of therapy. [​33​] An increase in activity level may also cause a fall in blood glucose 
levels. To aid in maintaining safe blood glucose levels subjects will be required to report to the study team if their 
blood glucose is over 250mg/dl on more than 2 consecutive measures or any value over 300mg/dl or  less than 
70mg/dl on any occasion. Symptoms of hypoglycemia (sweating, weakness, palpitations, confusion) will be 
reviewed with the participant at each visit. They will be advised to check their blood glucose if possible if such 
symptoms occur and to take one 15g glucose tablet (to be carried at all times) and repeat this every 15minutes until 
self-monitored blood glucose is over 80mg/dL or symptoms resolve. 
Table 3 Summary of Nutrient Administration Days 0-Day 14
 
Item: 
Intervention Group: 
Control Group: 
Ensure High Protein Shake  
(400kcal/800mls/100% protein RDA/day) 
Via tube* 
By mouth 
Unflavored Pedialyte Electrolyte Solution 
(80kcal/800mls/~50% electrolytes/day) 
By mouth** 
Via tube* 
Additional vitamins and electrolytes 
By mouth 
By mouth 
Ad Lib food from that provided 
By mouth 
By mouth 
Ad Lib “calorie-free” foods from provided list 
By mouth 
By mouth 
*If unable to administer by tube the remainder to be taken by mouth 
**Optional artificial flavoring (provided) may be added by subject if they wish to the orally ingested Pedialyte to increase
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
  
 
palatability. This will be documented in the daily log. 
 
 
Day 7: Subjects will return to the clinic for review of log and caloric intake. Medications will be triturated at the study
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
clinician’s discretion in an attempt to attain euglycemia. The position of the tube tip will be assessed per FDA approved
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
procedure by reinsertion of the subject’s own transmitting stylet and the tube will be repositioned if not located beyond the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
Ligament of Treitz. 
 
Day14: Baseline measures will be repeated. The position of the tube tip will be assessed per FDA approved procedure by
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
reinsertion of the subject’s own transmitting stylet and then removed. All uneaten food will be returned for caloric intake
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
determination, activity monitor download. 
 
Day 15-Day 28: The subject will maintain a symptom and blood glucose log for 14 days after the removal of the tube. 
 
Day 21: Subjects will return to the clinic for review of log and activity monitor. Medications will be titrated at the study
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
clinician’s discretion in an attempt to attain euglycemia. 
  
Day 28: Exit outcome measures similar to those at Baseline and Day 14. 
 
Possible Additional Study Visits: Subjects will be seen at additional visits by the study team if they so request or if deemed
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
  
 
appropriate by the study clinicians. Subjects will be encouraged to contact the study team if they do not feel well or if
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
certain criteria are met. These specific criteria are: 
a.
Self monitored blood glucose values over 200mg/dL on 3 scheduled checks 
b.
Failure to ingest prescribed amounts of fluid 
c.
Failure to administer tube feed on 2 successive occasions 
d.
A morning oral temperature reading >37.2ºC (98.9ºF) or an afternoon temperature of >37.7ºC (99.9ºF)  
e.
Pain that does not resolve spontaneously over 3 or 4 hours or with use of acetaminophen 
Additional visits may be scheduled to determine position of the tube or to reposition the tip if it was not successfully placed
 
 
 
 
  
 
 
 
 
 
  
 
 
   
 
 
 
 
in the jejunum at the initial visit or if the tube is blocked in which case attempts will be made to unblock it or it may be
 
 
  
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
  
  
 
 
replaced. 
 
10 
 

Ver 3.11.14 
 
4.0
DRUG/​DEVICE​ INFORMATION  
 
4.1
DRUGS  
The only drug to be use is optional generic acetaminophen in recommended dose. 
4.1.1
Standardized amounts of non-prescription nutrients and electrolyte solution will be administered 
both orally and via NJ tube. 
4.1.1.1
High Protein Shake ® Abbott Park, Illinois, U.S.A. All subjects will take 800mls 
divided equally and administered 4 times a day. This will provide the following each 
day:  100% of RDA high quality protein, 400kcal, 800mls water, 20% of potassium 
requirements and 16% of sodium requirements (Per 14 fl oz. bottle: 210 calories, 
protein 25g, carbohydrate 23g, fat 2.5g, sodium 240mg, potassium 290mg) 
4.1.1.2
Unflavored Pedialyte ® Abbott Park, Illinois, U.S.A. All subjects will take 800mls of 
Pedialyte /day divided equally and administered 4 times a day. This will provide the 
following each day:  80kcal, 800mls water, approx. 40% of potassium requirements and 
40% of sodium requirements. ​(​Osmolality, mOsm/kg H2O: 250; per liter: Sodium, 
mEq: 45; Potassium, mEq: 20; Chloride, mEq: 35; Zinc, mg: 7.8; Dextrose, g: 25; 
Calories: 100). No artificial sweeteners or flavors. 
4.1.1.3
The only difference is that the intervention group will receive the High Protein Shake 
via the tube and take the Pedialyte orally whereas the control group will take the 
Pedialyte via tube and the High Protein Shake by mouth. 
4.1.1.4
 Klor-Con 1 tablets 10meq/tab. All subjects will take 2 tablets/day which will provide 
remaining potassium requirements (approximately 30-50% of RDA). 
4.1.1.5
Table salt (generic): All subjects will take 3grams/day (half a teaspoon) to provide 
remaining sodium requirements (approximately 30-50% of RDA). 
4.1.2
Kirkland Signature Daily Multi Vitamins & Minerals 1/day will provide 50-100% of RDA 
4.1.3
Kirkland Signature Calcium 600 Mg + D3 500 Tablets​ 2/day will provide 80-100% of RDA 
4.1.4
Liquid acetaminophen (generic) 500mg/15mls: if desired for throat pain. Maximum 60mls/day. 
4.2
Glucose tablets (generic) 15g: to be carried at all times for use in the event of hypoglycemia. 
4.3
For anesthesia of the pharynx if requested by the study participant and no contraindication: viscous 
lidocaine 2% (generic): 5 mL gargled for 3 minutes and may be swallowed. One dose only 5minutes prior 
to the procedure. The maximum dose for this agent is no more frequently than every 3 hours with a 
maximum of 8 doses per 24-hour period.[​34​] Contraindication:  Hypersensitivity to lidocaine or any 
component of the formulation; hypersensitivity to another local anesthetic of the amide type. 
 
  
 
4.4
DEVICE 
 
CORTRAK​®​ 2 ENTERAL ACCESS SYSTEM (EAS™) ​[​35-41​]  
This system is FDA cleared for placement of enteral feeding tubes without x-ray confirmation. A transmitting stylet is used 
to place the enteral tube. The tip of the stylet contains an electromagnetic transmitter that generates a real-time signal as the 
feeding tube is inserted and advanced to the desired placement. The signal from the transmitting stylet is tracked throughout 
the placement procedure via a lightweight receiver unit (Smart Receiver Unit: SRU) that is placed on the patient’s xiphoid 
process. A monitor triangulates the signal from the SRU and displays a real-time representation of the feeding tube tip’s 
passage as it proceeds down the esophagus and into the preferred placement position — gastric, duodenal, or jejunal. (See 
Fig 6) 
 
Fig 6 
 
11 
 

Ver 3.11.14 
 
 
Advantages of ​CORTRAK​®​ 2 ENTERAL ACCESS SYSTEM (EAS™) 
Safe 
a.
Eliminates or significantly reduces patient exposure to X-ray  
b.
Confirms accurate placement quickly​.  
c.
Clinicians are able to identify misplaced tubes immediately to significantly reduce adverse events  
Accurate 
a.
In a multi-center study 99.5% of placements correlated with abdominal X-ray​. 
b.
89% -100% success rates reported with gastric, jejunal, and duodenal placement  
c.
Additional depth cross-sectional view may more accurately predict location compared with X-ray 
Fast 
a.
Real-time visualization of the relative tube tip position eliminates waiting time for X-ray 
confirmation 
Support 
a.
CORPAK’s Clinical Educators assist with implementation planning, on-site education training programs and 
customized protocol development with hospital education teams  
b.
CORTRAK 2 Learning Center at www.cortraksystem.com provides high-quality, on-demand training and training 
checklist, link to Mosby’s Nursing Skills)  
Flexibility 
a.
Choice of operating mode for easy upload of data for training, review, or research  
b.
2D and 3D views provide more information than X-ray for confident placement without X-ray  
Evidence 
a.
Growing clinical research base demonstrating system’s safety and efficacy  
b.
Used by more than 200 healthcare systems worldwide  
Of note the PI and CoI have been trained and certified in use of the EAS and have been using it in preliminary studies in 
outpatients. To date they have placed approximately 25 jejunal tubes with this system without incidence. 
 
 
Intraoral Anchor (see Fig 7) 
For the purposes of this study we will secure the tube intraorally rather than through the nasopharynx to the skin. 
The rationale for this is: 
a.
To minimize discomfort to the subject due to placement of the tube through the sensitive nasopharynx 
b.
To eliminate the risk of complications in the nasopharynx such as nose bleed, sinusitis and malposition 
c.
To improve social acceptability of the study by rendering the tube inapparent to the casual observer. 
d.
To simplify tube maintenance by avoiding the need for taping or other means of securing the tube externally. 
To achieve this we will: 
12 
 

Ver 3.11.14 
 
a.
Modify a standard orthodontic molar band on an upper molar with the addition of a metal channel to anchor the 
tube in the mouth. The channel is welded to the buccal surface of the band. 
b.
Place standard orthodontic spacers following standard orthodontic procedure on either side of the selected molar 
c.
Approximately 1 week later place the modified molar band 
d.
Modify a standard CORPAK enteral feeding tube by cutting off the access port and leaving only an approximately 
4mm flange 
e.
Pass the tube through the channel in the alert subject so that the tube passes through the lateral oropharynx and 
then, by standard placement technique, to the jejunum 
f.
Fashion an integrated tube cap to close the tube when not in use 
g.
Provide a syringe with a blunt tapered tip to administer fluids per protocol. 
 
Fig 7 
 
This modification of standard placement and anchoring of the tube has been reviewed and evaluated by multidisciplinary 
study team members comprising a bioengineer, orthodontists, ENT specialist and upper GI surgeon and endoscopist who 
report: 
a.
The flange is strong enough to hold the tube at the proximal end of the channel as it is ​solvent bonded/glued per 
the manufacturers ​and will not deform or detach thereby rendering the risk of distal displacement extremely low. 
Per scientific adviser Professor Khoshnevis: “​Because the access port is solvent bonded to the tube and both the 
tube and the access port are made of a reasonably strong polymer material, the chance of the tube ever being 
released from the oral anchor due to its separation from the access port segment is nearly zero. Using solvent is 
perhaps the best way of adhering parts made of materials that can be dissolved by the solvent agent as the adhered 
components become monolithic.”(Personal and email communication). 
b.
The modified molar band is a minor variant of a standard orthodontic molar band and is very secure and similarly 
renders the risk of distal displacement of the tube extremely low. 
c.
The tube position in the oropharynx is lateral to sites triggering the gag reflex and allows for virtually normal 
speech, swallowing and eating with minimal or no gagging and is virtually undetectable by others. 
d.
Some discomfort and mild pain (maximum ~4 out of 10) can be expected mostly in the first 4-5days of use. This 
can be eased with several maneuvers including change of body position and acetaminophen in standard dose. 
e.
The discomfort and pain can be expected to be minimal after the first 5 days such that the subject is barely aware 
of the tube’s presence. 
f.
There is minimal risk of throat or gastrointestinal complications with a 10 French jejunal tube placed in the 
described manner and for duration of 2 weeks. 
 
5.0
SELECTION​ AND WITHDRAWAL OF RESEARCH SUBJECTS  
5.1 Inclusion Criteria: 
●
18-70 years of age 
●
Type 2 diabetes on oral antidiabetic medication 
●
BMI ​>​30kg/m​2 
●
A1C <9%  
5.2 Exclusion Criteria: 
●
Use of any of the following medications: dipeptide-peptidase IV (DPP-IV) inhibitors (e.g., sitagliptin), GLP-1 
analogs (e.g., exenatide) or medication that could alter glucose tolerance (e.g. steroids) 
●
Contraindication to tube (e.g. Prior upper gastrointestinal bleed, or history of easy bleeding, altered foregut 
anatomy due to obstruction or surgery)  
●
Known cardiovascular disease other than controlled hypertension. 
●
Pregnancy or unwilling to take contraception 
●
Active esophagitis 
●
Known ​hiatal hernia  
●
Active gastric​ ​ulcer and/or duodenal ulcers,  
●
Previous restrictive surgery of​ ​the gastrointestinal tract  
●
Crohn’s disease  
●
Active cancer  
●
History of gastrointestinal  hemorrhage  
13 
 

Ver 3.11.14 
 
●
Known upper gastrointestinal lesions with potential to bleed 
●
Use of NSAIDs or anticoagulants 
●
Psychiatric disorders other than mild depression 
●
Likely inability to adhere to study protocol including alcohol or drug dependent​ ​patients  
●
Type I diabetes, 
●
 Liver, kidney or​ ​multi-organ dysfunction. 
●
Known eating disorders  
●
Inability to attend scheduled or unanticipated study visits 
●
Known prior abdominal problems or operations that could lead to adhesions or strictures and that could prevent the 
spontaneous passage of a 10 French jejunal tube if it were to dislodge distally. 
5.3 Withdrawal Criteria 
●
Non-adherence to study instructions by subject for more than 2 days. 
●
Any request by subject 
●
Fever over 100.4 F, more than 1 episode of vomiting, gastrointestinal upset not relieved by reduction in tube feed, 
dislodged anchor or tube, average daily glucose over 200mg/dL on 2 or more days, weight change of >7% in first 
week of tube use. 
●
Clinical judgment of the PI (reason to be specified) 
 
6.0
 ​STRATIFICATION/DESCRIPTIVE FACTORS/RANDOMIZATION SCHEME 
The site of enteral feeding tube placement will be randomized.  Subjects will be not be stratified. 
 
7.0
STUDY AGENT ADMINISTRATION OR INTERVENTION​ ​AND TOXICITY MANAGEMENT ​PLAN 
               NA 
 
8.0 ​ASSESSMENT OF EFFICACY AND SAFETY 
 
Safety of this study plan has been reviewed with the multidisciplinary team and by review of relevant literature.  
Steps taken to minimize potential risks are summarized in table 4. 
 
The following study team members, who are all USC faculty members have evaluated aspects of this protocol related to
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
their area of expertise and have concluded that this is a low risk study, with potential benefit outweighing possible harm. 
 
Specifically: 
a.
Stability and safety of oral anchor: Orthodontists: Dr Hongsheng Tong DDS and Dr John Pham DDS (resident) 
b.
Stability of orojejunal tube in anchor: Bioengineer Professor Behrokh Khoshnevis PhD 
c.
Safety of orojejunal tube in oropharynx: ENT: Dr Uttam Sinha MD 
d.
Safety of orojejunal tube in gastrointestinal tract and low calorie diet similar to that post gastric bypass surgery:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Foregut and Bariatric Surgeon and Endoscopist: Dr Peter Crookes MD 
e.
Safety of nutritional intervention and diabetes management: Endocrinologists Dr Elizabeth Beale MD, WeiAn Lee DO 
 
Oropharyngeal Care with Anchor and Tube In-Situ 
Standard care as used following placement of orthodontic braces will be recommended. Subjects will be advised to brush and floss 
their teeth after every meal. Complications are not anticipated even in subjects with type 2 diabetes. Acetaminophen liquid 
may be taken in standard doses if needed to decrease tube discomfort.  
The anchors will be manufactured in-house by Dr Tong using medical-grade orthodontic materials. The anchor will be bonded to the 
molar using fluoride containing cement to minimize the unlikely possibility of dental decay. The anchors will be placed and 
removed by the study team orthodontists. 
It is considered highly unlikely that infection will develop due to use of the tube anywhere along its path. If fever develops for any 
reason however, whether considered due to the intervention per se or to intercurrent illness, the subject will be removed 
from the study. 
 
Very Low Calorie and Low Calorie Tube Feeds 
Cappello et al [​26​] reported on the use of a very low calorie nasogastric tube feed diet (200-260 kcal/d) for 10 day periods with no 
14 
 

Ver 3.11.14 
 
serious complications in a group of over 19,000 people. The problems encountered were damage to the external part of the 
tube (e.g. shaving) 2%, “gastric hypersecretion” (nos) 2%, nausea and vomiting 1%, and intolerance to the nasal tube 
0.03%. The following were not observed: ulceration or bleeding due to the tube, b​reakage of the tube in esophagus or 
in the​ stomach, p​erforation or bleeding of the stomach.  Sukkar et al [​42​] in another similar smaller study reported 
on 22 ​patients who received 10 days of ​very low calorie nasogastric tube feeds (200-260 kcal/d). Subjects ​were monitored 
for the​ ​following side effects relating to enteral nutrition (abdominal​ ​distension and pain, diarrhea, vomiting, reflux, 
naso-gastric​, ​tube obstruction, de-positioning or accidental removal of the​ ​naso-gastric tube, others) and those related to the 
very low calorie/high protein diet (cardiac arrhythmia, ketosis, hypoglycemia, others). Out of 26 patients enrolled, 3 
patients (9 %) were withdrawn due to poor compliance and 1 (3 %) for allergy to milk protein. Of the remaining 22 subjects 
there were no reported major complications or side effects resulting from the enteral nutrition in any patient. In particular, 
no cardiac arrhythmias were reported, nor diarrhea or cramps. The following were reported: constipation (3/22; 13.6 %), 
dizziness or headache during the first 2 days [20/22; 90.9 % (only two needed medication)], general weakness (3/22; 13.6 
%), halitosis (5/22; 22.7 %) controlled by sugarless mint chewing-gum. The naso-gastric tube was blocked in 3 patients and 
required repositioning.  
 
Enteral Feeding Tube Placement 
Although enteral tube placement is a common clinical practice and is performed by lay individuals in the home
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
environment when necessary, it has been associated with serious complications including malposition into the airway,
 
 
  
 
 
 
 
 
 
 
 
 
 
 
perforation of the trachea and esophagus and pneumothorax. These complications occur almost exclusively during blind
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
intubation in sedated, unconscious or otherwise poorly responsive patients and neonates and when the tube is placed
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
through the nasopharynx. In this study we will use the EAS​TM system and CORTRAK tubes which have demonstrated
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
greater safety than standard blind placement due to real time visualization during placements. Tubes will be placed
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
following manufacturer’s recommended procedure to minimize risk. Furthermore all subjects will be fully alert throughout
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
the procedure and able to interact with the trained investigator who is placing the tube; tubes will be placed by the oral
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
route with a “swallow down” placement technique rather than a “push” technique. These precautions can be expected to
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
minimize the already very low rate of complications that can arise during tube placement, making a serious problem
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
extremely unlikely. Aspiration of stomach contents may occur if the subject has not fasted prior to tube placement. If on
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
enquiry the subject has not fasted then the test will be cancelled. Blind intubation requires x-ray confirmation prior to tube
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
use to minimize complications related to tube misplacement however the EAS​TM system is FDA approved to not require
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
x-ray confirmation of placement thereby avoiding risks associated with radiation. [​35-41​] 
 
Ambulatory Use of Jejunal Tube for 14 Days Nasal and oral feeding tube for feeds are standard accepted clinical practice
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
for subjects requiring nutritional support up to 30 days. ​The American Gastroenterological Society recommends that
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
consideration be given to replacing a naso or oro enteral feeding tube with a percutaneous tube after 30days. [​43​] ​Although
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
not currently widely accepted as medical therapy, the ketogenic enteric diet has been extensively used in Europe and is now
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
available through franchises internationally. Although the underlying physiological approach that we are hypothesizing is
 
 
 
 
 
 
 
 
 
 
 
 
  
markedly different to this diet, it does demonstrate that use of enteral tubes for 10 days is feasible and acceptable to many
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
  
 
individuals having been used in over 24,000 subjects in one center. [​26​] This study involves a variant of standard enteral
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
tube feeding, the main differences being the indication for the intervention and the rate of the tube feed administration.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects in this study will be far more closely monitored than in standard clinical practice. Some discomfort can be
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
expected to occur in the throat due to the tube and may be relieved by slight relocation of the tube to relieve pressure or
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
overall body repositioning of the e.g. lying down after prolonged sitting at a desk. Discomfort tends to decrease after 4-5
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
days of use. Acetaminophen will be offered to subjects for use if desired. If fever develops suggestive of local infection
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
then the subject will be withdrawn from the study and referred to their usual care provider for further management. This
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
problems has not however been reported in thousands of patients undergoing the ketogenc enteric diet.[​26​, ​42​]  
 
Inadvertent Dislodgement of the Tube 
Enteral feeding tubes not infrequently become accidentally dislodged in general use. This is considered highly unlikely to
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
cause problems in this study as the tube will be anchored entirely intraorally. Most displacement is due to inadvertent
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
pulling on the extracorporeal part of the tube by a sedated or otherwise confused patient, or failure of tape to maintain
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
position of the tube. If the tube were to slip through the anchor it is anticipated that it would pass directly through the
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
gastrointestinal tract. Per co-investigator Dr. Peter Crookes a tube that becomes dislodged and is swallowed will almost
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
certainly pass spontaneously through the intestinal tract as long as there are no abnormalities in the intestine such as
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
adhesions or strictures and the chance of the tube being retained and requiring endoscopic or surgical removal is so low that
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
it does not need to be mentioned as a risk to subjects. We will exclude all subjects with a history of abdominal infections or
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
  
 
 
 
 
 
surgeries or other illnesses that could lead to strictures or adhesions. 
15 
 

Ver 3.11.14 
 
 
Evidence that the molar band is very secure is supported by several references: 
●
Banks, P. and T.V. Macfarlane, ​Bonded versus banded first molar attachments: a randomized controlled clinical 
trial.​ J Orthod, 2007. ​34​(2): p. 128-36; discussion 111-2.[​44​]  
●
Millett, D.T., et al., ​Adhesives for bonded molar tubes during fixed brace treatment.​ Cochrane Database Syst Rev, 
2011(6): p. CD008236[​45​]  
●
Nazir, M., et al., ​Banding versus bonding of first permanent molars: a multi-centre randomized controlled trial.​ J 
Orthod, 2011. ​38​(2): p. 81-9.[​46​]  
 
The following table and figure from Nazir et al [​46​] summarizes this information and provides data that the molar 
band is a very secure system especially in the short term as used in this study. 
  
 
 
Ensuring participants won’t chew through the tube if they have bruxism  
The tube anchor is located on the upper posterior buccal molar. The 140cm tube immediately passes backwards from the
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
anchor to the lateral oropharynx where it descends straight down into the gastrointestinal tract. It is maintained in this
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
position by gravity and peristalsis. The tube is thus unable to move medially across the occlusal surface of the teeth and
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
hence bruxism does not pose a risk. 
16 
 

Ver 3.11.14 
 
 
Mouth guards 
Participants are not required to wear a mouth guard either while awake or asleep as the tube is positioned well lateral and
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
posterior occlusal surfaces of the teeth. 
 
Precautions to be taken to prevent the tube being accidentally swallowed 
The following precautions will be taken to decrease the chance that the tube will be accidentally swallowed: 
Participants will be asked to monitor for any loosening of the molar band daily and also to monitor for any evidence of
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
abrasion or wear on the intraoral portion of the tube. They will do this by checking that the band is secure manually and by
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
looking for wear on the tube when it is brought slightly forward to be attached to the syringe for each tube feeding. They
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
will be requested to report any concerns in this regard to the study team as soon as it is detected. They will also be told how
 
 
 
 
 
 
  
 
  
 
 
 
 
 
   
 
 
 
 
 
 
 
to remove the band or tube if it should become so loose or worn that it could dislodge spontaneously. Furthermore to
 
 
 
 
 
   
 
 
 
 
 
 
  
 
 
 
 
 
decrease risk of the band becoming dislodged the band will be kept in place for as short a period as possible.  
 
Procedure if the tube is accidentally swallowed and how it will be retrieved.  
The risk of accidental swallowing of the tube is considered to be extremely remote due to the precautions taken in the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
design of the anchor and tube as described above. If the tube is accidentally swallowed the participant will contact the study
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
team and co-investigator Dr. Peter Crookes who is a foregut surgeon and endoscopist. He will arrange appropriate
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
follow-up for the participant. Clinical back-up in this area will be provided by co-investigator Dr. James Buxbaum
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(gastroenterologist and endoscopist). References for the following data can be found in the recent systematic review of the
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
topic of ingested foreign bodies in adults. [​47​] As most ingested foreign bodies pass through the gastrointestinal tract
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
without any difficulty conservative treatment by means of close observation will likely be the approach used. This is the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
treatment of choice as the tube is blunt and narrow (<2.5 cm diameter) and the tip will already be past the pylorus.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Spontaneous passage can be expected within 4–6 days. Rare cases have been reported where it has taken up to 4 weeks to
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
   
  
pass a foreign object. Until the tube has passed, the participant will be asked to monitor their stools continuously. No
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
change in eating behavior will be required during this period. If the tube is not passed after about 1 week then weekly
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
outpatient x-ray examination will likely be recommended in order to document, the foreign body’s passage. As the tube is
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
radiopaque its passage can be documented​. ​(See product insert uploaded at iSTAR #18.2). 
If the tube does not pass spontaneously then it may be retrieved by Dr. Crookes or Dr. Buxbaum using upper or lower
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
endoscopy. It is unlikely that emergency esophagogastroduodenoscopy (EGD) will be required as this is recommended
  
 
 
 
 
 
 
 
 
 
 
 
 
 
when the esophagus is completely occluded (because of the risk of aspiration and/or pressure necrosis), when the ingested
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
object has a sharp point or edge (because of the risk of perforation, with ensuing mediastinitis or peritonitis), and when a
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
battery has been ingested (because of the risk of necrosis and fistula formation)-none of which can reasonably be expected
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
to occur in this study. Similarly even an urgent but non-emergency EGD (within 12 to 24) hours is unlikely to be required
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
  
 
 
as this is recommended for non-occluding esophageal foreign bodies such as magnets. Recovery of a foreign body by
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
means of colonoscopy is not common practice according to the available data as after the ileocecal valve has been passed
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
the foreign body is usually excreted without any complications.  
There is a remote possibility that surgery (including the option of minimally invasive laparoscopic surgery) could be
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
required to remove the tube. This has become progressively more unusual as endoscopic retrieval rates improve. The only
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
absolute indication for surgery is reported to be perforation which is highly unlikely to occur with the blunt soft tube.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relative indications for surgery after ingestion of foreign bodies exist in the case of complications that cannot be resolved
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
endoscopically or after unsuccessful attempts at endoscopic recovery.  
 
Data to support claims that the tube will almost certainly pass spontaneously through the intestinal tract without
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
any intestinal abnormalities 
A recent review by Ambe et al [​47​]summarizes findings from numerous articles on the topic of ingested foreign bodies in
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
  
adult. It has been widely reported that the majority of foreign bodies in the gastrointestinal tract will pass spontaneously but
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
that about 10-20% will require non-operative intervention and less than 1% will require surgery. In the current study, in the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
very unlikely event that the tube were to be accidentally ingested, the rate of spontaneous passage can be expected to be far
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
higher than 80%. The reasons for this are as follows: 
a.
Impaction most often occurs at areas of acute angulation or physiologic narrowing. The esophagus is the most frequent
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
site of blockage (50–75%) because of physiological narrowing at the cricopharyngeal sphincter, the aortic arch and the
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
diaphragmatic hiatus. Other relatively narrow and angled areas are the duodenum and the entrance to the jejunum at
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
the Ligament of Treitz. In this study the tube will be placed by the study team through the esophagus, the duodenum
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
17 
 

Ver 3.11.14 
 
and beyond the ligament of Treitz so obstruction at these levels would be extremely unlikely. Once through the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
esophagus, the majority of ingested foreign bodies pass through the alimentary tract uneventfully.  
 
b.
Patients with prior gastrointestinal tract surgery or congenital gut malformations account for a large number of
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
obstructions. We will reduce the risk of obstruction by the exclusion criteria of a history of abdominal infections or
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
surgeries or other illnesses that could lead to strictures or adhesions. 
 
c.
The participant will be excluded from the trial if the tube cannot be passed through the esophagus, stomach, duodenum
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
and jejunum initially, the commonest sites for impaction.  
 
Daily Activities with Tube In-Situ 
The intra-oral tube placement renders it inapparent to the casual observer. This allows the subject to avoid embarrassment
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
or unwanted explanations due to tube use and to continue with routine activities. The subject may experience discomfort or
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
some anxiety due to tube placement and if rapid weight loss occurs, may experience increased fatigue. As this is a
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
voluntary study the subject will have made an informed decision to have a tube in-situ for 2 weeks. Where possible, the
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
tube will be placed during a 2 week period when the subject will be able to adhere to the study routine and rest
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
appropriately. Ease of mind will likely be increased for the subject by knowing that at any time they desire they can remove
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
the tube themselves, withdraw from the study and/or contact the study team. 
 
Symptoms due to Jejunal Nutrient Administration 
Subjects may experience dumping symptoms of nausea, palpitations, sweating and abdominal pain during or for about 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
hour after jejunal nutrient infusion. The dose of the nutrient administered will be selected by the subject to achieve
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
comfortable satiety. They will stop administering nutrient if they experience unpleasant symptoms. Symptoms, if they
 
 
 
 
 
 
  
 
 
 
 
  
 
occur are usually mild and are transient and self-limited. We will exclude potential subjects from the study if they have any
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
known cardiovascular disease (other than controlled hypertension) to minimize potential risks to the subject associated with
 
 
 
 
 
 
  
 
 
  
 
 
 
 
possible palpitations in association with dumping syndrome. 
 
Venipuncture 
This study involves venipuncture of a peripheral vein. This is associated with a small risk of minor bleeding and infection at 
the puncture site. To minimize this risk, aseptic precautions will be used.  
 
Risk of Hypoglycemia or Hyperglycemia 
Alteration in diet and physical activity could lead to alterations in blood glucose: both hyperglycemia and hypoglycemia. 
To minimize the risk of these complications the following precautions will be made: 
a.
All participants will have the symptoms and signs of hyperglycemia and hypoglycemia reviewed 
with them as well as recommended management at each visit starting with the recruitment visit 
when the protocol is reviewed. 
b.
As most diabetic patients eating very low-calorie diets have marked improvement in 
hyperglycemia with blood glucose concentrations falling within the first one to two weeks oral 
hypoglycemic drugs will be discontinued for the first week of therapy. [​33​] An increase in 
activity level may also cause a fall in blood glucose levels. To aid in maintaining safe blood 
glucose levels subjects will be required to report to the study team if their blood glucose is over 
250mg/dl on more than 2 consecutive measures or any value is over 300mg/dl or  less than 
70mg/dl on any occasion.  
c.
Information on managing hypoglycemia is provided in the FREE TO GO Study Instructions 
given to the participant.  
 
Table 4 Summary of Steps Taken to Minimize Risk of Intervention 
Concern 
Precaution 
Modified anchoring of orojejunal tube 
Development by senior bioengineering and orthodontic specialists 
Safety of orojejunal tube for 2 weeks 
Potential risks reviewed with senior ENT and bariatric surgeon and deemed 
highly unlikely to occur 
Subjects will monitor their temperature and the tube position daily and report 
to the study team if any concerns 
18 
 

Ver 3.11.14 
 
Physical and psychosocial discomfort due to 
ambulatory use of orojejunal tube for 2 weeks 
Intraoral anchoring makes tube inapparent to observers.  They will be 
encouraged to take acetaminophen and take other steps to decrease discomfort 
of tube particularly in first few days of use. They will be shown how to 
remove the tube themselves at any time if they so desire 
Back-up in event of distal tube displacement 
Senior bariatric surgeon on study team 
Safety of very low calorie diet for 2 weeks in 
subjects with type 2 diabetes 
Close monitoring by specialist endocrinologist with adjustment of medication 
if needed. All subjects can take food and liquid ad lib. Mandatory minimum 
480 kcal/d; 1.6litres fluid/day; 100% RDA high quality protein; 100% RDA 
electrolytes, minerals and vitamins. 
Hyper- and Hypo-glycemia 
Oral hypoglycemic drugs will be discontinued for the first week of therapy 
and participants will contact the study team if their glucose levels are less 
than 70mg/dL or over 250mg/dL. 
Participants will be educated on the symptoms of hypo- and hyper- glycemia 
and provided wth instruction and glucose tablets for the management of 
hypoglycemia. 
 
19 
 

Ver 3.11.14 
 
9.0
CLINICAL AND LABORATORY EVALUATIONS AND STUDY​ CALENDAR 
Table 5 
 
Preparation 
With Tube 
Follow Up 
 
Approximately 
Day-14 
Approximately 
Day -7 
Day 0 
Day 7 
Day 14 
Day 21am 
Day 28 
Location ALL at EDWARD R. ROYBAL CHC 
Clinical 
Evaluation 
By orthodontist 
for suitability 
for molar band 
By orthodontist 
for placement of 
molar band 
(may require 2 
visits) 
By MD  
Vital Signs 
Symptoms 
Physical Exam 
Weight  
Waist 
Hip  
By MD  
Vital Signs 
Symptoms  
Physical Exam 
Weight  
Waist 
Hip 
By MD  
Vital Signs 
Symptoms  
Physical Exam 
Weight  
Waist 
Hip  
By MD  
Vital Signs 
Symptoms  
Physical Exam 
Weight  
Waist 
Hip 
By MD  
Vital Signs 
Symptoms  
Physical Exam 
Weight  
Waist 
Hip  
Labs  
(total 20 cc/visit) 
none 
none 
BMP​a 
Fasting: 
Adiponectin​b 
Leptin​b 
FGF-19​b 
Insulin​b 
Glucose​b 
C-peptide​b 
GLP-1​c 
Ghrelin​ c 
PYY​ c 
CCK​ c 
Bile Acids​ c 
FT3​ c 
 
BMP​a 
Fasting: 
Adiponectin​b 
Leptin​b 
FGF-19​b 
Insulin​b 
Glucose​b 
C-peptide​b 
GLP-1​c 
Ghrelin​ c 
PYY​ c 
CCK​ c 
Bile Acids​ c 
FT3​ c 
 
BMP​a 
Fasting: 
Adiponectin​b 
Leptin​b 
FGF-19​b 
Insulin​b 
Glucose​b 
C-peptide​b 
GLP-1​c 
Ghrelin​ c 
PYY​ c 
CCK​ c 
Bile Acids​ c 
FT3​ c 
Procedure 
Place spacers 
Place band 
Place tube 
Place FitBit 
Body 
Composition 
Provide 1 week 
food 
Return all 
uneaten food 
 
Provide 1 week 
food 
Return all  
uneaten food 
 
Remove tube and 
band 
Body 
Composition 
 
Remove FitBit 
Body 
Composition 
Other Activities 
none 
Start Daily Flow 
Sheet 
Review daily 
flowsheet 
including 
self-monitored 
blood glucose 
 
Review daily 
flow sheet 
including 
self-monitored 
blood glucose 
Download 
FitBit/recharge 
Review daily flow 
sheet including 
self-monitored 
blood glucose 
Download 
FitBit/recharge 
Review daily 
flow sheet 
including 
self-monitored 
blood glucose 
Download 
FitBit/recharge 
Review daily 
flow sheet 
including 
self-monitored 
blood glucose 
Remove  and 
download FitBit 
Food Intake 
Ad lib  
Day 0-Day 14 Tube Bolus and Provided Diet 
Ad lib free foods Supplements 
 Day 14-Day 28 Ad lib 
a​at USC DORI   ​b​at Cedars-Sinai  ​c​at Cedars Sinai when funds available 
 
 
20 
 

Ver 3.11.14 
 
10.0
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS 
 
Primary aim: weight change immediately following the intervention period between the study groups 
Secondary aims: to compare the following within and between groups:  
a.
From Day 0 to Day 14: caloric intake (as determined by consumption of provided food)  
b.
From Day 0 to Day 14: weight change (within group) 
c.
From Day 0 to Day 28: weight change  
d.
From Day 0 to Day 14 and also from Day 0 to Day 28: waist and hip measurement, hormones and 
biochemical measures, physical activity , body composition , select symptoms, medication use, average 
self-monitored blood glucose level 
 
 
11.0
SPECIAL INSTRUCTIONS: 
 
Samples will be collected by the PI or IRB approved research assistant from peripheral venipuncture. 
The investigator will draw 20cc fasting blood at Day 0, 14 and 28 visits into a prepared tube containing aprotinin. This will 
be kept on ice and centrifuged, separated and aliquoted within 30mins of blood draw. Samples will then be stored at -20 
degrees centigrade until transferred on ice to collaborator for assay. 
 
Study Costs: All costs for this study will be paid from study funds. There will be no patient care costs incurred for payment 
from non-study funds. Costs covered by the study include study visits, supplies, equipment, blood draws, biochemical 
analysis and subject reimbursement.  
 
12.0
DATA COLLECTION AND MONITORING 
 
Confidentiality of Discussions:​ The privacy of the research subject will be protected by having discussions regarding the 
study and confidential health matters in a private room in the Roybal CHC or by telephone from a private office. 
Initial and follow-up Case Report Forms (CRF): ​All data will be entered on IRB approved clinical medical record forms. 
All data will be kept in a locked cabinet in Dr Beale’s office when not in use. 
Data Security and Confidentiality​ Data will only be accessible by the primary investigator and co-investigators and research 
assistants for the purposes of the study. Data will be transcribed from the CRF to a non-network computer, password 
protected, accessible only by the investigators for the purposes of the study. Each enrolled patient will be assigned a study 
number and all data will be stored under this study number with no linkage to patient identifiers.  Data will also be stored 
by Dr. Ionut in her computer protected computer database using a study specific identifier developed specifically for the 
study. The computer is password protected and is in a room accessible only to the laboratory personnel. All personnel have 
been HIPAA trained. 
When the study is completed the data or data set will be maintained in a de-identified form on the PI’s computer. Identifiers 
will be destroyed at the earliest opportunity consistent with the conduct of the research and/or clinical needs and will be 
maintained no longer than 2 years after completion of the study. 
 
Source Documentation and Timeliness of CRF Completion.​ The CRF will be completed by the research staff daily. Data 
will be stored on REDCap. 
 
Retention of Study Record:​ Study data will be retained for 5 years after publication. At this time or in case non-publication, 
the data will be destroyed. 
Data Management:​ Data will be recorded on clinic record forms and will be entered into a database system for subsequent 
statistical analysis. Potential data errors will be detected by plotting frequency tables or histograms on outcome and 
exposure variables and data ranges will be checked to identify potential outliers. The frequency of missing values will be 
counted for each variable at each of the follow-up time points. Cross-tables will be used to verify the logical validity of 
related variables.  
 
 
 
13.0
STATISTICAL CONSIDERATIONS 
SC CTSI statisticians have provided assistance with study design. This is a pilot study. As such power studies are not 
appropriate.  Effect sizes and parameter estimates derived from this study will be used in the design and power calculations 
21 
 

Ver 3.11.14 
 
for future studies The primary aim is to compare weight change from Day 1 to Day 14 (the intervention period)  between 
the 2 study groups.  
The secondary aims are to compare the following between study groups:  
a.
From Day 1 to Day 14: caloric intake  
b.
From Day 1 to Day 28 (the intervention and follow-up period): Weight change  
c.
From Day 1 to Day 14 and also from Day 1 to Day 28:  
i.
waist and hip measurement, 
ii.
 hormones and biochemical measures, 
iii.
physical activity  
iv.
body composition  
v.
symptoms 
vi.
medication 
vii.
self-monitored blood glucose 
Due to the exploratory nature of this study, it is possible that clinically relevant effects will be observed that do not reach 
statistical significance. Nevertheless, based on the work of Lingvay et al[​27​] we could consider a 30% difference between 
sites in weight loss between the groups to be clinically relevant. 
 
Data will be presented as mean +/- S.E.M. Differences between groups will be analyzed by one-way ANOVA 
followed by a Student’s t-test for independent samples. A non-parametric test (Wilcoxon Rank) will be performed 
when appropriate. Change over time will be assessed with ANOVA for repeated measurements. In case of a 
significant result a post hoc analysis will be performed with the Student’s ttest. All analyses will be performed 
using SPSS for Windows Version 12.0 (SPSS Inc., Chicago, USA). 
 
 
14.0
REGISTRATION GUIDELINE 
 
14.1
Specify phone number to register the patients: 626 232 3548. 
Subjects will be randomized to caloric or non-caloric jejunal feeding.  
Forms and records needed for registration:  
14.2.1
Informed Consent  
14.2.2
Daily self-monitoring sheet 
14.2.3
Visit work sheet  
 
At the time of registration, two copies of a signed and dated patient Informed Consent form with Bill of 
Rights will be available (an original for patient’s medical chart; one copy for the patient; and the other for 
the PI’s file).  
 
 
15.0
BIOHAZARD COMTAINMENT 
Blood sampling and IV line placement will follow standard biohazard safety precautions.  
Sharps will be disposed of in clinic sharps containers. 
 
16.0
ETHICAL AND REGULATORY CONSIDERATIONS 
 
All institutional and Federal regulations concerning the Informed Consent form will be fulfilled.  The study will be 
conducted in adherence to ICH Good Clinical Practice. 
 
 
 
 
 
 
 
22 
 

Ver 3.11.14 
 
 
 
 
APPENDIX A: FREE TO GO NUTRITION 
Note:​ ​If the listed items are not available the PI may authorize similar substitutes 
TABLE A: Provided Study Nutrients: Must be Taken Every Day  
Item 
Amount and Route 
Ensure ​High Protein Shake 
800mls/day  by tube or mouth as advised 
Pedialyte Solution  
800mls/day by tube or mouth as advised 
Klor-Con10m potassium tablets 
2 tablets/day 
Table salt  
Half a teaspoon/day 
Kirkland Signature Daily Multi Vitamins & Minerals:  
1 tablet/day 
Kirkland Signature Calcium 600 Mg + D3 500 tablets:  
2 tablets/day 
 
 
 TABLE B: Provided Food: To be eaten as desired 
Item Provided 
Brand 
#Servings 
provided 
Cals/serving 
Oatmeal 
Quaker Instant Variety 
10 
130 
Eggs 
California Ranch Fresh 
10 
90 
Milk 
Real Fresh 
12 
150 
Soft tortilla 
Guerrerro Flour 
48 
130 
Sliced brown bread 
Nature’s Own Whole Grain Wheat 
22 
60 
Sliced white bread 
Nature’s Own Whole Grain White 
22 
75 
Soup 
Progresso 
10 
130 
Frozen entrée 
Lean Cuisine 
10 
280 
Non-frozen meal 
Nissin Bowl 
10 
280 
Canned meal 
Campbells Chunky 
10 
140 
Pudding 
Snackpack 
8 
110 
Cookies 
Quaker Chewy Variety 
8 
100 
Ice cream 
Dreyers No Sugar 
16 
90 
Canned fruit 
Delmonte Light Variety  
8 
70 
Apples 
5 apples (fresh) 
5 
95 
Bananas 
5 bananas (fresh) 
5 
105 
Orange juice 
Minute Maid 
12 
140 
Frozen Vegetables 
Essential 
10 
40 
Water Flavor Enhancer  
Dasani Drops (Mixed Berry flavor) 
96 
0 
 
TABLE C: Optional Items: Not provided. Can be added to other intake if desired 
Vegetables (1 cup raw) 
Asparagus  
Bean sprouts  
Beet greens  
Broccoli  
Brussels sprouts  
Cabbage, (all kinds)  
Chard  
Cauliflower  
Celery 
Chicory 
Collard greens  
Cucumbers  
Egg plant  
Endive  
Escarole  
Green beans  
Green onion  
Kale  
Lettuce (all kinds)  
Mushrooms  
Mustard greens  
Okra  
Peppers (green or red)  
Radishes  
Spinach  
Squash, summer  
Tomatoes  
Turnip greens  
Watercress  
Wax beans  
Zucchini 
Drinks 
Bouillon, clear broth; (no fat)  
Diet or Sugar free soda  
Diet or Club soda  
Coffee/tea  
Sugar free drink mixes  
Sugar Substitutes  
(ALL sugar free)  
Hard candy and gum  
Gelatin  
Jam/Jelly  
1-2 tablespoon pancake syrup  
Desserts & Fruits:  
Cranberries  
Lemons 
Condiments  
1 tablespoon ketchup or  mustard  
Unsweetened pickles  
23 
 

Ver 3.11.14 
 
Lemon juice  
Tomato juice  
Vegetable juice  
Sweet 'n Low or Equal  
2 tablespoon whipped topping  
 
2 tablespoon low calorie  salad 
dressing  
3 tablespoon taco sauce  
 
TABLE D: Provided. To be taken for hypoglycemia Low blood glucose) or if concerned that sugar is low. 
Glucose tablets (generic) 
15g 
Qty 30 
 
TABLE E: Study Supplies 
Item 
Quantity 
Blood glucose strips 
150 
Thermometer 
1 
Fitbit Activity Monitor 
1 
Glucose meter  
As needed 
Glucose meter battery 
As needed 
Study log 
4 
Syringe to administer tube feed 
15 
Tylenol liquid (500mg/15mls)  
As needed 
Maximum 
60mls/day 
Syringe to administer tube feed 
15 
 
 
 
24 
 

Ver 3.11.14 
 
APPENDIX B: FREE TO GO STUDY INSTRUCTIONS 
 
24 HOUR CONTACT INFORMATION 
Dr. Beale (626) 232-3548 or pager (213) 287-0123  Dr. Lee 
(626) 367-7860 or pager (323) 203-0362  
Thank you for your participation in the FREE TO GO STUDY 
You are requested to follow the following instructions for the 2 weeks you have the tube in place. 
1.
4 times a day ​(before your usual meals and before sleeping) 
▪
Check and record your blood glucose level with your meter 
▪
Record your throat discomfort or pain level 
▪
Record if you have taken any pain medication since your last log 
▪
Check to make sure the molar band is secure and the tube undamaged 
▪
Record if you have any gastrointestinal upset 
▪
Give yourself the tube feed 
▪
Record the amount of tube feed you gave 
▪
Record the time taken to give the tube feed 
▪
Record how much of the tube feed (if any) was taken by mouth 
▪
Flush the tube with 10mls of water 
▪
Take the required oral feed  
2.
Every day: 
▪
Check and record your temperature at least once a day 
▪
Take the mineral and vitamin supplements you have been given 
▪
Write down the name and dose of any medication you take 
▪
Write down the type and amount of all food you eat and drink you take and keep ALL the leftovers 
▪
Wear your activity monitor at all times except when it might get submerged in water. 
▪
Be alert for symptoms of low blood glucose (hypoglycemia). These can include sweating, weakness,
 
 
 
 
 
 
 
 
 
 
 
 
 
 
palpitations and confusion. If any of these symptoms occur you should check your blood glucose if
 
 
  
 
 
 
 
 
 
 
 
 
 
  
possible and take one 15g glucose tablet (to be carried at all times) and repeat this every 15minutes
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
until your blood glucose is over 80mg/dL or the symptoms have gone. 
3.
Record any other comments​ you would like to make in the comments section 
4.
Contact the Study Team at any time you have concerns or questions 
5.
You should contact the study team as soon as possible  if any of the following occur: 
▪
You develop a fever of over ​100.4 F (38.0 C) 
▪
You have a vomiting episode 
▪
You have 2 episodes of diarrhea 
▪
You are unable to give the tube feeds as requested for whatever reason twice in a row 
▪
You do not take the recommended oral feeds and supplements twice in a row 
▪
Either the anchor or tube is not in the correct position or are loose or damaged. 
▪
You do not want to continue with the study and want to remove the tube 
▪
You have 2 or more blood glucose levels over 250mg/dL twice in a row  
▪
You have any blood glucose level less than 70mg/day or over 300mg/dL 
6.
If you are concerned about your health and for whatever reason you are unable to reach the study team you
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
should seek professional medical advice.for example by contacting your primary care doctor. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
25 
 

Ver 3.11.14 
 
 
 
Helpful Hints 
1.
You should be able to carry on with your usual daily acitivties while the tube is in place. However you may 
feel more tired than usual and have some pain or discomfort so you should try to get adequate rest. 
2.
Some discomfort or pain can be expected when the tube is in place and this does not mean that you have a 
serious problem or an infection. It will likely occur mostly in the first few days and after that you will likely 
hardly be aware that the tube is in place. The discomfort or pain will often go away by itself or if you change 
your position or move the tube a few centimeters. You can take Tylenol liquid to help with this.too. You may 
find things that  relieve or worsen the discomfort. If you do, please document this in your log. 
3.
Sometimes the tube gets kinked and you may not be able to give the tube feed. You can try to undo the kink 
by pulling back on the tube up to about the length of your hand (about 6inches  or 15cms) and trying again. 
4.
Sometimes the tube gets blocked with tube feed. This can be prevented by flushing the tube after every feed. 
If you think the tube maybe blocked with feed you can try to unblock it by injecting water. You should not use 
any other liquid to unblock the tube 
5.
If you really do not want to have the tube in any more you can pull it out yourself. The tube is 140cm long. 
All you have to do is gently and smoothly pull the tube out of the mouth. 
 
26 
 

Ver 3.11.14 
 
APPENDIX C: FREE TO GO DAILY LOG (TUBE PERIOD)  
DATE: ________ STUDY DAY_____________ STUDY ID #______________________ Page 1/2 
GENERAL  
SID#: 
 
Morning 
Midday 
Afternoon 
Evening 
Time: 
 
 
 
 
Blood glucose value: 
 
 
 
 
Throat discomfort or pain  
0 (none)-10 (really bad): 
 
 
 
 
Tylenol taken since last log  
     Y 
N 
     Y            N 
     Y           N 
     Y            N 
Temperature ( at least once a day): 
 
 
 
 
Is molar band secure? 
    Y 
N 
   Y              N 
   Y              N 
   Y              N 
Is the tube smooth and undamaged? 
    Y 
N 
   Y              N 
   Y              N 
   Y              N 
GI upset 0 (none)-10 (really bad): 
 
 
 
 
Tube feed given  
     Y 
N 
     Y 
N 
     Y 
N 
     Y 
N 
Amount tube feed taken by mouth  (if any) 
mls: 
 
 
 
 
Required oral feed taken 
     Y 
N 
     Y 
N 
     Y 
N 
     Y 
N 
Time taken to give tube feed (minutes) 
 
 
 
 
Tube flushed  
     Y 
N 
     Y 
N 
     Y 
N 
     Y 
N 
Multivitamin taken? Y/N 
     Y 
N 
             --- 
            --- 
            --- 
Klor-Con taken Y/N 
            --- 
     Y 
N 
            --- 
     Y 
N 
Calcium and Vit D taken? Y/N 
     Y 
N 
             --- 
    Y 
N 
           --- 
Additional salt taken? Y/N 
            --- 
             --- 
            --- 
     Y 
N 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
 
FOOD AND DRINK* 
 
 
Morning 
Midday 
Afternoon 
Evening 
Item and amount 
 
 
 
 
 
Item and amount 
 
 
 
 
 
Item and amount 
 
 
 
 
 
Item and amount 
 
 
 
 
 
Item and amount 
 
 
 
 
 
27 
 

Ver 3.11.14 
 
Item and amount 
 
 
 
 
 
Item and amount 
 
 
 
 
 
Item and amount 
 
 
 
 
 
Item and amount 
 
 
 
 
 
Item and amount 
 
 
 
 
 
*Please use additional sheets if necessary 
 
 
 
 
 
 
 
 
DATE: ________ STUDY DAY_____________ STUDY ID #______________________ Page 2/2 
 
COMMENTS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28 
 

Ver 3.11.14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Please use additional sheets if necessary 
 
 
 
FREE TO GO DAILY LOG (BEFORE AND AFTER TUBE PERIOD) 
 
 
DATE: ________ STUDY DAY_____________ STUDY ID #______________________ Page 1/1 
GENERAL  
SID#: 
 
Morning 
Midday 
Afternoon 
Evening 
Time: 
 
 
 
 
Blood glucose value: 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
Med Taken (name/ dose): 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
29 
 

Ver 3.11.14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
17.0 REFERENCES 
 
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3.
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4.
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30 
 

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12.
Olivan, B., et al., ​Effect of weight loss by diet or gastric bypass surgery on peptide YY3-36 
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Kaushik, N., et al., ​Enteral feeding without pancreatic stimulation.​ Pancreas, 2005. ​31​(4): p. 
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22.
Welch, I.M., C.P. Sepple, and N.W. Read, ​Comparisons of the effects on satiety and eating 
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Rolls, B.J. and L.S. Roe, ​Effect of the volume of liquid food infused intragastrically on 
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25.
Sumithran, P., et al., ​Ketosis and appetite-mediating nutrients and hormones after weight 
loss.​ Eur J Clin Nutr, 2013. ​67​(7): p. 759-64. 
26.
Cappello, G., et al., ​Ketogenic enteral nutrition as a treatment for obesity: short term and 
long term results from 19,000 patients.​ Nutr Metab (Lond), 2012. ​9​(1): p. 96. 
27.
Lingvay, I., et al., ​Rapid Improvement of Diabetes After Gastric Bypass Surgery: Is It the 
Diet or Surgery?​ Diabetes Care, 2013. 
28.
Jackness, C., et al., ​Very Low Calorie Diet Mimics the Early Beneficial Effect of Roux-en-Y 
Gastric Bypass on Insulin Sensitivity and Beta-Cell Function in Type 2 Diabetic Patients. 
Diabetes, 2013. 
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Bray, G., ​Dietary therapy for obesity​, in ​UpToDate​, B. DS, Editor. 2013, UpToDate in 
Waltham, MA. 
30.
Hall, K.D., et al., ​Quantification of the effect of energy imbalance on bodyweight.​ Lancet, 
2011. ​378​(9793): p. 826-37. 
31 
 

Ver 3.11.14 
 
31.
Silk, D.B., ​The evolving role of post-ligament of Trietz nasojejunal feeding in enteral 
nutrition and the need for improved feeding tube design and placement methods.​ JPEN J 
Parenter Enteral Nutr, 2011. ​35​(3): p. 303-7. 
32.
Jazet, I.M., et al., ​Sustained beneficial metabolic effects 18 months after a 30-day very low 
calorie diet in severely obese, insulin-treated patients with type 2 diabetes.​ Diabetes Res Clin 
Pract, 2007. ​77​(1): p. 70-6. 
33.
Management of obesity by severe caloric restriction​. PSG Publishing Co., Littleton, MA  
34.
Mogensen, S., et al., ​New lidocaine lozenge as topical anesthesia compared to lidocaine 
viscous oral solution before upper gastrointestinal endoscopy.​ Local Reg Anesth, 2012. ​5​: p. 
17-22. 
35.
CORTRAK® 2 ENTERAL ACCESS SYSTEM™​. 2013; Available from: 
http://www.corpakmedsystems.com/cortrak.html​. 
36.
Gray, R., et al., ​Bedside electromagnetic-guided feeding tube placement: an improvement 
over traditional placement technique?​ Nutr Clin Pract, 2007. ​22​(4): p. 436-44. 
37.
Koopmann, M.C., et al., ​A team-based protocol and electromagnetic technology eliminate 
feeding tube placement complications.​ Ann Surg, 2011. ​253​(2): p. 287-302. 
38.
Holzinger, U., et al., ​Jejunal tube placement in critically ill patients: A prospective, 
randomized trial comparing the endoscopic technique with the electromagnetically visualized 
method.​ Crit Care Med, 2011. ​39​(1): p. 73-7. 
39.
Ackerman, M.H. and D.J. Mick, ​Technologic approaches to determining proper placement 
of enteral feeding tubes.​ AACN Adv Crit Care, 2006. ​17​(3): p. 246-9. 
40.
Taylor, S.J., A.R. Manara, and J. Brown, ​Treating delayed gastric emptying in critical 
illness: metoclopramide, erythromycin, and bedside (cortrak) nasointestinal tube placement. 
JPEN J Parenter Enteral Nutr, 2010. ​34​(3): p. 289-94. 
41.
Deane, A.M., et al., ​Evaluation of a bedside technique for postpyloric placement of feeding 
catheters.​ Crit Care Resusc, 2009. ​11​(3): p. 180-3. 
42.
Sukkar, S.G., et al., ​Feasibility of protein-sparing modified fast by tube (ProMoFasT) in 
obesity treatment: a phase II pilot trial on clinical safety and efficacy (appetite control, body 
composition, muscular strength, metabolic pattern, pulmonary function test).​ Med J Nutrition 
Metab, 2013. ​6​: p. 165-176. 
43.
Kirby, D.F., M.H. Delegge, and C.R. Fleming, ​American Gastroenterological Association 
technical review on tube feeding for enteral nutrition.​ Gastroenterology, 1995. ​108​(4): p. 
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44.
Banks, P. and T.V. Macfarlane, ​Bonded versus banded first molar attachments: a 
randomized controlled clinical trial.​ J Orthod, 2007. ​34​(2): p. 128-36; discussion 111-2. 
45.
Millett, D.T., et al., ​Adhesives for bonded molar tubes during fixed brace treatment. 
Cochrane Database Syst Rev, 2011(6): p. CD008236. 
46.
Nazir, M., et al., ​Banding versus bonding of first permanent molars: a multi-centre 
randomized controlled trial.​ J Orthod, 2011. ​38​(2): p. 81-9. 
47.
Ambe, P., et al., ​Swallowed foreign bodies in adults.​ Dtsch Arztebl Int, 2012. ​109​(50): p. 
869-75. 
 
32