The study is intended to provide insight into the clinical feasibility of the Exilis* system as a therapy for obesity, including:* Providing initial human safety data on the Exilis* system, * Gaining an understanding of how to individually titrate…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Obesitas
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. To obtain first-in-human experience with the Exilis* system, including
initial clinical feasibility and safety data, as well as data on device
performance (e.g., recharge durations and intervals) and use conditions (e.g.,
stimulation amplitudes, lead impedances). These data will inform decisions
about whether to pursue further clinical studies with the Exilis* system, or
whether the Exilis* system or the way it is used should be modified before
pursuing further clinical studies.
2. To gain an understanding of what sensations, if any, subjects feel during
GES treatment, and what level and type of sensations subjects find acceptable
and comfortable during chronic daily treatment. If subjects do report
sensations during GES, data collection on these sensations will be used to
develop sensory-based programming procedures for the Exilis* system to aid
identifying the highest comfortable pulse amplitude for chronic treatment
during a single brief clinic visit.
Secondary outcome
1. To determine whether GES delivered with the Exilis* system delays gastric
emptying, and whether any GES-induced delay in emptying persists under
prolonged chronic daily treatment. Medtronic*s preclinical research has found
that GES like that delivered by the Exilis* system delay gastric emptying in
rodents, canines and swine, and that a larger GES-induced delay in gastric
emptying in rodents correlates with a larger GES-induced reduction in feeding.
Delayed gastric emptying has been linked to early and prolonged satiation in
both humans and animals , and is suspected to be part of the mechanism of
action by which the Exilis *GES system may reduce food intake and body weight.
Thus an objective of the study is to confirm whether GES-induced delays in
gastric emptying observed in animal models can be replicated in humans.
2. To determine whether GES delivered with the Exilis *system suppresses
post-meal gastric contractile activity. Medtronic*s preclinical research has
included numerous measurements of gastric contractile activity in canines
following the ingestion of a solid meal. These tests have repeatedly shown that
GES treatments like that delivered by the Exilis* system suppress post-meal
gastric contractile activity that occurs during the processing of a meal into
chyme before it passes into the small intestine. This effect is at least part
of the mechanism by which GES delays gastric emptying. In canines this
post-meal motility suppression effect of GES has been measured using a
manometric catheter placed in the gastric antrum, and observed directly via
fluoroscopy following a barium-labeled test meal. In the proposed study,
gastric contractile activity will be monitored noninvasively using a SmartPill
gastrointestinal pressure, pH and temperature monitoring device that will be
ingested with water by the subject just prior to consumption of the breakfast
test meal.
3. To determine whether GES delivered with the Exilis* system reduces post-meal
plasma glucose and insulin concentrations. Delaying gastric emptying slows the
rate at which ingested nutrients are absorbed into the bloodstream, blunting
the rise in blood glucose and insulin levels following a meal. This effect may
be beneficial in reducing episodes of postprandial hyperglycemia that are
associated with an increased risk of mortality from cardiovascular diseases.
Medtronic*s preclinical research has found that delivery of the Exilis* GES
signal reduces postprandial glycemic levels in both diabetic and obese
non-diabetic rats. Measurement of the post-meal profiles of plasma glucose and
insulin during gastric emptying tests conducted with GES On and GES Off during
the study will provide a test of whether the postprandial glycemic control
effects of GES observed in rats can be duplicated in humans. Further assays of
the blood samples collected in conjunction with the gastric emptying test meals
may also be analyzed to explore whether GES similarly alters plasma levels of
gut peptides involved in regulating food intake and body weight, including
GLP-1, PP, PYY, CCK, ghrelin and leptin.
4. To determine whether GES delivered with the Exilis* system reduces caloric
intake during a standardized ad libitum solid meal consumed in a controlled
setting. Medtronic preclinical research has found that GES treatments like that
delivered by the Exilis* system reduce food intake in rodent, canine and swine
models. Meal pattern analysis in rodents with 24 hour ad libitum food access
found that GES-induced reductions in food intake were due to reduced meal size,
with the number and timing of daily meals being unaltered. Caloric intake will
be measured in study subjects during an ad libitum lunch test meal consumed in
a controlled setting on two occasions*once with GES On and once with GES Off*
will be used to test whether the GES-induced reduction in meal size observed in
animals can be replicated in humans.
5. To characterize data on any changes in other physiological parameters,
medication usage, and psychometric assessment scores that occur during chronic
daily GES treatment with the Exilis* system. Physiological parameters of
interest for this objective include body weight, waist and hip measurements,
pulse rate, blood pressure, blood lipids, fasting blood glucose, HbA1c levels
and reported levels of physical activity, as measured by International Physical
Activity questionnaire (IPAQ). Psychometric assessments will include general
(SF-12) and obesity-specific (IWQoL-Lite) quality of life instruments, the
Three Factor Eating Questionnaire (TFEQ), and visual analog scale ratings of
hunger and fullness.
Background summary
The prevalence of obesity is rising worldwide, and the majority of adults in
the United States and many developed countries are overweight or obese. It is
estimated that 1.5 billion adults worldwide are overweight (BMI>25) and 500
million are obese (BMI *30)1. The increasing prevalence of obesity in the US
has been accompanied by an even more rapid rise in the prevalence of severe
obesity (Class II and III, BMI *35)2. Rates of severe obesity among US adults
more than tripled between 1986 and 2000, and by 2008 an estimated 33 million US
adults or 14.3% of the adult population were severely obese.
Obesity is associated with higher rates of disability and all-cause mortality,
and the obese have increased incidences of type II diabetes, cardiovascular
disease, musculoskeletal disorders, sleep apnea, fatty liver disease and
certain cancers4. Obesity and its co-morbidities are estimated to claim more
than 100,000 lives5 and add $147 billion to health care costs annually in the
US alone6. The health consequences of obesity increase with BMI, concentrating
most of the disease and cost burden of obesity among the severely obese.
Severely obese adults have all-cause mortality rates nearly twice as high as
normal weight individuals7, and are 5.5 times as likely to have type II
diabetes, three times more likely to require anti-hypertensive medications, and
1.7 times more likely to be diagnosed with heart disease8. While annual health
care expenditures for US adults with Class I obesity (30* BMI<35) have been
estimated to be 25% greater than for normal weight adults, this excess in
health care cost over normal weight adults doubles to 50% for adults with Class
II obesity (35*BMI<40), and quadruples to 100% for the Class III obese
(BMI*40)9.
Even though many severely obese patients achieve weight loss through behavioral
treatments focused on diet and exercise, only a small minority of these
patients succeed in maintaining their losses. As a result, the expected weight
loss efficacy of these interventions declines to near zero within five years
from the start of treatment.
Available pharmacotherapy options for obesity are limited. The lipase inhibitor
orlistat is currently the only anti-obesity drug approved for long term use in
the US. This agent has, at best, modest efficacy that is only sustained as long
as patients continue taking the drug. More than 90% of patients who try
orlistat cease taking it within one year. This rapid attrition in usage, which
is in part driven by the adverse gastrointestinal side effects of the drug,
makes the expected long term efficacy orlistat minimal. At present, prospects
for more effective new pharmacotherapies appear poor. Recent years have seen
several candidate anti-obesity drugs fail to obtain regulatory approval due to
inadequate efficacy, adverse side effects, or both.
The only treatments for severe obesity that have demonstrated sustained long
term efficacy are bariatric surgeries, with the two dominant procedures being
adjustable gastric banding (AGB) and Roux-en-Y gastric bypass (RYGB). These two
procedures account for over 80% of the more than 350,000 bariatric surgeries
performed annually worldwide. In a recent systematic review of weight loss
outcomes in comparative studies of these procedures, AGB and RYGB patients lost
averages of 31-55% and 51-76% of their excess body weight at one year,
respectively. These weight losses were accompanied by resolution of type II
diabetes in 40-77% and 72-100% of diabetic AGB and RYGB patients, and
resolution of hypertension in 27-70% and 61-81% of hypertensive AGB and RYGB
patients at one year post-surgery. In the longer term, both AGB and RYGB
patients regain, on average, a portion of their maximal weight loss, with this
regain tending to be greater in the case of AGB. Long term follow-up of a large
cohort of bariatric surgery patients in the Swedish Obese Subjects study,
however, found that gastric banding and bypass patients maintained an average
of 68% and 77% of their one-year weight loss a decade after surgery, and that
this degree of sustained weight loss was sufficient to significantly reduce
their all-cause mortality relative to matched controls who did not undergo
bariatric surgery.
Compared to other widely used medical interventions, bariatric surgery has been
found to be a cost-effective means of extending longevity and improving quality
of life, and there is some evidence that the costs of bariatric surgery are
more than fully offset by the reductions in future medical costs associated
with the resolution or improvement of obesity-related comorbid conditions.
Despite growing evidence of the benefits of bariatric surgery and a rapid rise
in procedure volumes over the past two decades, only a small percentage of
obese patients who are candidates for bariatric surgery under the standard
criteria*(BMI *40, or 35* BMI <40 with an obesity-related comorbidity)*will
ever undergo bariatric surgery17. A likely reason for this is that patient
acceptance is limited by the of 10-20% rates of serious complications reported
for AGB and RYGB surgeries, the potential for permanent adverse side effects
(e.g., chronic vomiting, GERD, dumping syndrome, nutrient deficiencies), and
the fact that the alterations in anatomy associated with these procedures are
difficult or impossible to reverse in response to a poor outcome.
Study objective
The study is intended to provide insight into the clinical feasibility of the
Exilis* system as a therapy for obesity, including:
* Providing initial human safety data on the Exilis* system,
* Gaining an understanding of how to individually titrate stimulation amplitude
to a level that subjects will find comfortable under chronic daily treatment,
* Collecting data on acute gastrointestinal (GI) and feeding responses to GES
to confirm whether effects of GES observed in animal models can be replicated
in human subjects, and
* Characterize changes in physiologic parameters (e.g. weight, blood pressure)
with GES
Study design
Up to 20 obese (BMI 35-45) subjects, aged 21-64, will be implanted with the
Exilis* system in this study at up to three clinical sites in Europe and the
United States. Chronic daily GES treatment will be delivered in the context of
a single arm study design, with all subjects receiving active GES, 16 hours per
day, during waking hours. The chronic daily GES treatment settings will be
determined by a series of amplitude titration assessments. Data will be
collected at regular clinic visits for up to five years or more from implant.
All subjects will receive a Health and Wellness program consisting of six In
Person visits with a dietitian and 15 on-line educational lessons.
Study subjects will also complete a suite of gastrointestinal (GI) function
tests, and a solid meal satiety test. The tests will be repeated twice during a
pair of 6-7 hour clinic visits following the first month of daily GES treatment
as part of an acute response cross-over experiment. GES will be On during one
of these testing visits and Off during the other, in a randomly assigned order,
with subjects blinded to test day treatment assignments. Apart from during
these two visits, subjects as well as clinicians will be unblinded with respect
to GES delivery throughout the study. Each of these testing visits will be
preceded by a washout period, approximately one week in duration, during which
subjects will receive no GES treatment. As detailed in Section 6 of this
protocol, with the proposed sample size of 20 implanted subjects, this acute
cross-over experiment component of the study has ample statistical power to
detect clinically significant changes in gastric motility and solid meal
satiety test caloric intake across GES Off and GES On treatment days. Duration
between test visits will vary with those participating in the substudy.
Intervention
The medical intervention consists of the implantion of the exilis system using
a laprorascopic surgical procedure. Placement of two electrodes near the
pylorus and the remaining of the system in the abdominal area closely under the
skin.
Study burden and risks
The potential risks have been classified according to if the potential risk is
related to the Procedure, Device, or Therapy. The following are the identified
potential risks associated with the Exilis System and its intended use. There
may be additional risks related to study participation that are unknown at this
time.
There are procedural-related risks associated with the laparoscopic surgery,
including death. The risks associated with this surgery are risks that can
occur with other laparoscopic surgeries. Some of these risks, such as the risks
of general anesthesia, are increased for a person who is obese.
Subjects may benefit from their participation in the study through weight loss
and an improvement in its associated comorbidities and/or quality of life
indices.
Indirect benefits include: the knowledge that the subject is contributing to a
better understanding of the use of GES for Obesity.
Endepolsdomein 5
Maastricht 6229GW
NL
Endepolsdomein 5
Maastricht 6229GW
NL
Listed location countries
Age
Inclusion criteria
1. Subject is 21-64 years of age inclusive at time of screening;
2. Subject is willing to sign and date an informed consent and a data privacy authorization for their Participation;
3. Subject has a BMI of 40-45 kg/m 2 or 35-39.9 kg/m2 with at least one weight-related comorbidity diagnosed prior to screening; (e.g. , obstructive sleep apnea, nonalcoholic steatohepatitis, hypertension, dyslipidemia, gastroesophageal reflux disease, asthma, venous stasis disease, severe urinary incontinence, debilitating arthritis);
4. If subject is diagnosed with diabetes mellitus, must be Type 2 diabetes diagnosed within the last 7 years, currently treated with diet, exercise and /or oral agents only, and with a HbA1c of *8% without significant complications due to their diabetes in the judgment of the principal investigator;
5. Subject must be an acceptable candidate for laparoscopic implant under general anesthesia of the Exilis* system in the opinion a qualified surgeon performing the implant and can anatomically accommodate all implanted hardware which includes the ability to palpate the rib cage at the intended ICC implant location;
6. Subject reports failure at prior weight loss attempts using non-surgical approaches;
7. Subject reports their weight as being within 5% of their current body weight for at least one year;
8. Subject must, if female, be at least two years post-menopausal (defined as two years without menses), or surgically sterile (must be documented), or must agree to the use of effective contraception (devices, oral or implanted) for the duration they are enrolled in the study;
9. Subject must, if female, be non-lactating, and if of child-bearing potential, have a negative serum pregnancy test result prior to implant;
10. Subject must speak and understand English or Dutch with sufficient proficiency to read, comprehend, and sign the informed consent document and privacy statement, and to communicate with study staff;
11. Subject must have regular access to the internet running one of the following browsers: Internet Explorer 8+, Firefox 3+, Safari 4+, or Google chrome;
12. Subject reports having regular sleeping hours that do not frequently vary due to night shift worker regular long distance travel across four or more time zones;
13. Subject is willing to comply with daily recharging of device up to 90 minutes daily;
14. Subject is willing to fast overnight with no food, water only, for up to 12 hours;
15. Subject is willing to swallow a large rounded pill capsule, approximately 1.3 cm in diameter
16. Subject is willing to complete all scheduled study visits and procedures as defined in the Informed Consent;
Exclusion criteria
1. Subject has a history of medical, surgical, or psychiatric conditions that, in the opinion of the Investigator, would limit study participation;
2. Subject has presence of untreated or inadequately treated DMS-IV AXIS I (or greater) disorder and/or significant problematic eating behaviors that could interfere with long-term goals; unrealistic expectations or surgical results; might lack social support, understanding of surgery or have ineffective coping mechanism, upon completion of psychological analysis.
3. Subject has evidence of clinically significant ECG abnormalities, in the opinion of the Investigator at the Screening Visit;
4. Subject is currently taking, or has taken in the past 3 months, any prescription or over-the- counter medications that, in the Investigator's opinion could interfere with the subject*s suitability for participation in the study, including in particular any medications taken for the purpose of weight loss or that have been shown to affect GI motility;
5. Subject has been diagnosed with an eating disorder within the past five years;
6. Subject had prior GI surgery (e.g. bariatric surgery, fundoplication, gastric resection or major upper abdominal surgery);
7. Subject has a history of inflammatory disease (e.g. Crohn*s disease or ulcerative colitis) of the GI tract;
8. Subject has a history of functional and/or motility disease (e.g., gastroparesis) of the GI tract;
9. Subject has a history of pulmonary embolism or blood coagulation disorders;
10. Subject has a history of gastric bezoar, diverticulitis, disorders of swallowing, dysphagia to food or pills, suspected strictures, fistulas, or physiological obstruction in the GI tract;
11. Subject has an allergy or sensitivity to wheat, egg, soy, milk, tree nuts, or orange juice, all of which my be contained in the test meals consumed for the study gastric emptying or solid meal satiety tests;
12. Subject has a known genetic cause of obesity (e.g., Prader-Willi Syndrome);
13. Subject currently has active implantable medical devices or wears external stimulation and/or drug delivery medical devices;
14. Subject reports anticipating undergoing an MRI examination during the study duration; or subject reports anticipating undergoing diathermy (shortwave diathermy, microwave diathermy or therapeutic ultrasound diathermy) during the study duration;
15. Subject is currently participating in any investigational drug, device or biologic study; and
16. Subject has a history of heart disease (e.g. angina, history of myocardial infarction, previously documented arrhythmia) that may increase the risk of sudden cardiac death, in the opinion of the Investigator.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL41872.068.12 |
| Other | www.ClinicalTrails.gov |