U.S. patent application number 10/358093 was filed with the patent office on 2004-09-02 for method and apparatus for treatment of gastro-esophageal reflux disease (gerd).
Invention is credited to Conrad, Timothy R., Evnin, Luke B., Knudson, Mark B., Tweden, Katherine S..
Application Number | 20040172084 10/358093 |
Document ID | / |
Family ID | 32907599 |
Filed Date | 2004-09-02 |
United States Patent
Application |
20040172084 |
Kind Code |
A1 |
Knudson, Mark B. ; et
al. |
September 2, 2004 |
Method and apparatus for treatment of gastro-esophageal reflux
disease (GERD)
Abstract
GERD is treated through a method and apparatus of stimulating
the body organ to accelerate a discharge of contents from the
duodenum of the patient to thereby encourage discharge of contents
from the stomach of the patient across the pyloric valve and into
the duodenum.
Inventors: |
Knudson, Mark B.;
(Shoreview, MN) ; Conrad, Timothy R.; (Eden
Prairie, MN) ; Evnin, Luke B.; (San Francisco,
CA) ; Tweden, Katherine S.; (Mahtomedi, MN) |
Correspondence
Address: |
MERCHANT & GOULD PC
P.O. BOX 2903
MINNEAPOLIS
MN
55402-0903
US
|
Family ID: |
32907599 |
Appl. No.: |
10/358093 |
Filed: |
February 3, 2003 |
Current U.S.
Class: |
607/40 |
Current CPC
Class: |
A61N 1/0551 20130101;
A61N 1/36007 20130101; A61N 1/05 20130101; A61N 1/3606 20130101;
A61N 1/36053 20130101; A61N 1/321 20130101; A61N 1/36071
20130101 |
Class at
Publication: |
607/040 |
International
Class: |
A61N 001/18 |
Claims
What is claimed is:
1. A method for treating gastro-esophageal reflux disease (GERD) of
a patient comprising: treating a body organ to accelerate a
discharge of contents through at least a portion of a small
intestine of the patient to thereby encourage discharge of contents
from a stomach of the patient across a pyloric valve of the patient
and into said small intestine.
2. A method according to claim 1 wherein said portion is a duodenum
of said patient.
3. A method according to claim 1 wherein said treating is a
stimulation selected to increase a pH of said contents of said
portion of said small intestine.
4. A method according to claim 1 wherein said treating is a
stimulation selected to decrease an osmolality of said contents of
said portion of said small intestine.
5. A method according to claim 1 wherein said organ is a pancreas
of said patient and said treating is a stimulation of said organ
selected to stimulate delivery of an exocrine secretion from said
pancreas to said portion of said small intestine.
6. A method according to claim 5 wherein said pancreas is
stimulated directly.
7. A method according to claim 5 wherein said pancreas is
indirectly stimulated by stimulating at least a nerve of said
pancreas.
8. A method according to claim 5 wherein said stimulation is
initiated by said patient.
9. A method according to claim 5 wherein said stimulation is
initiated by a controller operatively connected to stimulating
electrodes and having an input operatively connected to a
sensor.
10. A method according to claim 9 wherein said sensor senses a pH
level of said portion of said small intestine.
11. A method according to claim 9 wherein said sensor senses a
degree of filling of said portion of said small intestine.
12. A method according to claim 9 wherein said sensor senses a
degree of osmolality within said portion of said small
intestine.
13. A method according to claim 9 wherein said sensor senses a
degree of motility within said portion of said small intestine.
14. A method according to claim 1 wherein said treatment includes
delivery of a paralyzing agent to said pyloric valve.
15. A method according to claim 14 wherein said delivery is done in
conjunction with agents to manage acidity of a content of said
portion of said small intestine.
16. A method according to claim 15 wherein said agents are selected
from a group including H.sub.2 antagonists and PPI's.
17. A method according to claim 5 wherein said stimulation is an
electrical stimulation.
18. A method according to claim 17 wherein said stimulation is at a
frequency selected to encourage exocrine secretion without excess
endocrine secretion.
19. A method according to claim 1 wherein said treating is a
stimulation selected to encourage bile delivery to the portion of
said small intestine.
20. A method according to claim 1, wherein the body organ is a
duodenum of said patient.
21. An apparatus for treating gastro-esophageal reflux disease
(GERD) of a patient comprising: a generator for generating a
stimulation signal; a conductor for electrically connecting said
signal generator to a body organ to accelerate a discharge of
contents from a portion of said small intestine of the patient to
thereby encourage discharge of contents from a stomach of the
patient across a pyloric valve of the patient and into said portion
of said small intestine.
22. An apparatus according to claim 21 wherein said conductor is
selected to engage and stimulate a pancreas to produce and deliver
exocrine secretion to said portion of said small intestine.
23. An apparatus according to claim 21 wherein said conductor is
selected to engage and stimulate a pancreas to produce and deliver
endocrine digestive compounds to the blood of said patient.
24. An apparatus according to claim 21 comprising a controller to
initiate said signal generator.
25. An apparatus according to claim 24 wherein said controller is a
patient operated controller.
26. An apparatus according to claim 24 wherein said controller is
an automatic controller having sensors connected to body organs to
sense initiating events and to send a signal to said controller in
response to said events.
27. An apparatus according to claim 22 wherein said stimulation is
at a frequency selected to encourage exocrine secretion without
excess endocrine secretion.
28. An apparatus according to claim 21 wherein said conductor is
selected to stimulate delivery of bile to said portion of said
small intestine.
Description
I. BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] This invention pertains to the field of treatment of
gastro-esophageal reflux disease (GERD).
[0003] 2. Description of the Prior Art
[0004] Gastro-esophageal reflux is a physical condition in which
stomach acids reflux, or flow back from the stomach into the
esophagus. Frequent reflux episodes may result in a more severe
problem known as gastro-esophageal reflux disease (GERD). GERD is
the most common form of dyspepsia, being present in approximately
40% of adults in the United States on an intermittent basis and
some 10% on a daily basis as described in U.S. Pat. No. 6,098,629
Johnson et al., dated Aug. 8, 2000.
[0005] As indicated in Johnson et al., dyspepsia, or heartburn is
defined as a burning sensation or discomfort behind the breastbone
or sternum and is the most common symptom of GERD. Other symptoms
of GERD include dysphasia, odynophagia, hemorrhage, water brash and
pulmonary manifestations such as asthma, coughing, or intermittent
wheezing due to acid aspiration.
[0006] GERD is generally considered to be the result of a motility
disorder which permits the abnormal and prolonged exposure of the
esophageal lumen to acidic gastric contents. Hunt, "The
Relationship between the Control of pH and Healing and Symptom
Relief in Gastro-Oesophageal Reflux Disease", Ailment Pharmacol
Ther., 9 (Suppl. 1) pp. 3-7 (1995). Many factors are believed to
contribute to the onset of GERD. These include transient lower
esophageal sphincter (LES) relaxations, decreased LES resting tone,
delayed stomach emptying and an ineffective esophageal
clearance.
[0007] Treatments for GERD include lifestyle changes such as weight
loss, avoidance of certain foods (e.g., coffee, caffeine, alcohol,
chocolate) that exacerbate the symptoms of GERD and avoidance of
excessive bending. Elevation of the head of a patient's bed helps
prevent nocturnal reflux. While these avoidance strategies may be
helpful there is relatively little data pointing to the efficacy of
lifestyle modification for the treatment of GERD.
[0008] Certain medications used for treatment of GERD have been
administered for years with varying success. Conventional antacids
such as Tums.RTM. and Rolaids.RTM. may, in some patients, produce
short-term relief but often have side effects including diarrhea
and constipation.
[0009] Other drugs have been more effective at controlling GERD but
fail to treat underlying causes of the disease and have been proven
to be extremely expensive and not readily available to all patients
due to such expense. Examples of such drugs are H.sub.2-receptor
antagonists (which control gastric acid secretion in the basal
state) and proton pump inhibitors (which control meal-stimulated
acid secretion). Hunt, id. Both classes of drugs can raise
intragastric pH to or about 4 for varying durations. Hunt,
supra.
[0010] Surgery treatments are also known for the treatment of GERD
and include techniques for bulking the lower esophageal sphincter
such as techniques described in U.S. Pat. No. 6,098,629 Johnson et
al, Aug. 8, 2000. Other surgical techniques include placement of
pacemakers for stimulating muscle contractions in the esophageal
sphincter, the stomach muscles or in the pyloric valve. U.S. Pat.
No. 6,104,955 to Bourgeois, U.S. Pat. No. 5,861,014 to
Familoni.
[0011] A summary of GERD treatments can be found in DeVault, et
al., "Updated Guidelines for the Diagnosis and Treatment of
Gastroesophageal Reflux Disease", Amer. J. of Gastroenterology,
Vol. 94, No. 6, pp. 1434-1442 (1999).
[0012] Notwithstanding multiple attempts at various types of
treatment, GERD continues to be a serious disease proving to be
difficult to treat by any of the foregoing prior art techniques. In
view of the foregoing and notwithstanding various efforts
exemplified in the prior art, there remains a need for an effective
treatment for GERD. It is an object of the present invention to
provide a novel treatment and novel apparatus for the treatment of
GERD.
II. SUMMARY OF THE INVENTION
[0013] One inventive aspect of the present disclosure relates to
methods and devices for treating GERD by stimulating the duodenum
of a patient to accelerate gastric emptying.
[0014] According to a preferred embodiment of the present
invention, a method and apparatus are disclosed for treating
gastro-esophageal reflux disease of a patient. The method includes
stimulating a body organ to accelerate a discharge of contents from
a duodenum of a patient to thereby encourage discharge of contents
from a stomach of the patient across a pyloric valve of the patient
and into the duodenum. The apparatus of the invention includes a
signal generator for generating a stimulation signal. A conductor
electrically connects the signal generator to the body organ to
accelerate a discharge of contents from the duodenum of the patient
to encourage gastric emptying.
III. BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is a schematic representation of a gastric-emptying
feedback loop with a patient-controlled stimulator for stimulating
an organ of the loop; and
[0016] FIG. 2 is a view similar to FIG. 1 with an automatic
controller replacing the patient-controller of FIG. 1 and with
feedback circuits to the automatic controller schematically
represented.
IV. DESCRIPTION OF THE PREFERRED EMBODIMENT
[0017] With reference now to the various drawing figures in which
identical elements are numbered identically throughout, a
description of the preferred embodiment of the present invention
will now be described.
[0018] With initial reference to FIG. 1, a gastric emptying
feedback loop is shown schematically for ease of illustration. The
feedback loop illustrates a patient's stomach S which is provided
with food from the esophagus E. A lower esophageal sphincter LES is
shown positioned between the esophagus E and the stomach S. The
lower esophageal sphincter normally provides control of reflux of
stomach contents into the esophagus E.
[0019] On a proximal or lower end of the stomach S the stomach
discharges into the superior duodenum D which is an upper portion
of the intestines. The superior duodenum D and the stomach S are
separated by a pyloric valve PV which opens to permit gastric
emptying from the stomach into the duodenum D.
[0020] Also schematically illustrated in FIG. 1 are nerve paths N
providing signal flow paths from both the superior duodenum D and
the stomach S to the brain B. An efferent Vagal nerve VN connects
the brain B to the pancreas P of the patient. A conduit (pancreatic
duct PD) extends from the pancreas P and discharges into the
superior duodenum D.
[0021] The presence of food contents within the duodenum D (such
contents being referred to as "chyme") may prevent passage of
gastric content of the stomach S past the pyloric valve PV into the
duodenum D. As long as such gastric contents cannot be passed into
the duodenum D, such contents can be forced retrograde past the
lower esophageal sphincter LES and into the esophagus E creating
the symptoms and discomfort of GERD. The contents discharging from
the stomach S into the duodenum D are acidic (and high osmolality)
and reside in the duodenum D until pH is elevated (close to a
neutral pH of 6-7) and osmolality is normalized.
[0022] The elevation of pH and reduction of osmolality of chyme in
the duodenum D results from exocrine secretion being administered
from the pancreas P and from bile from the liver into the duodenum
D. This raises the pH and lowers the osmolality of the duodenum D
content permitting discharge from the duodenum D and thereby
permitting gastric emptying across the pyloric valve PV.
[0023] According to the present invention, gastro-esophageal reflux
disease (GERD) results from a derangement of the feedback loops
involved in upper GI digestion and motility control. This problem
encompasses receptors and reflexes that regulate the propulsive
contractions of the stomach, upper duodenum and biliary tree and
the secretions of the exocrine pancreas. The interaction of these
receptors and reflexes control gastric emptying (by coordinating
gastric propulsive contractions and sphincter [primarily pyloric]
tone) and regulate the pH and osmolality of the chyme in the
duodenum. This chemo-regulation is mediated through control of bile
delivery and stimulation of secretion by the exocrine pancreas of
fluid delivered to the superior duodenum. Chey et al., "Neural
Hormonal Regulation of Exocrine Pancreatic Secretion",
Pancreatology, pp. 320-335 (2001).
[0024] Normally, ingestate delivered to the stomach is mixed by low
intensity gastric mixing contractions with the enzymatic, ionic,
including hydrogen ion (H.sup.+), and water secretions of the
glands of the stomach. When the material is adequately reduced in
size and is a smooth consistency, the fluid, now called chyme, is
delivered to the ampulla of the small intestine by the much
stronger propulsive, or emptying, contractions of the stomach
coupled with transitory relaxation of the pyloric sphincter. This
material is at a very low pH (about 2) and high osmolality, which
activates receptors, including those for H.sup.+ and osmotic
pressure, which are abundant in the wall of the ampulla. This
receptor activation initiates the series of reflexes that cause
pancreatic exocrine secretion to be delivered into the superior
duodenum and ampulla. This fluid contains digestive enzymes, water
and buffering compounds to raise the pH, and reduce the osmolality,
of the chyme.
[0025] Once a neutral pH and physiological osmolality are achieved,
then propulsive contractions in the superior duodenum move the
chyme out of the superior portion into the length of the duodenum;
At which point the stretch and baro-receptors in the ampulla allow
the pyloric sphincter to relax and another bolus of gastric
contents is delivered into the ampulla by the peristaltic gastric
emptying contractions. This material, at a very low pH (less than
2), activates hydrogen ion (H.sup.+) on receptors of the ampulla
(upper most portion of the duodenum) causing the pancreatic fluids
to be delivered to the material in the ampulla restarting the cycle
as described above. Chapter 3, "The Stomach", Gastrointestinal
System, 2.sup.nd Ed., M. S. Long editor, Mosby Publisher, London
(2002).
[0026] If the control system is down regulated by, for example, by
increased pH of gastric contents entering the ampulla, feedback may
thereby be reduced from the H.sup.+ receptors in the duodenum that
stimulate pancreatic exocrine secretion and bile delivery to the
duodenum, then movement of chyme from the superior duodenum is
delayed, causing delay of gastric emptying. Mabayo, et al.,
"Inhibition of Food Passage by Osmeprazole in the Chicken",
European J. of Pharmacology, pp. 161-165 (1995).
[0027] In GERD, this reflex is inhibited in such a way that the
stomach empties more slowly so that the gastric emptying
contractions force gastric contents to flow retrograde into the
esophagus. This is a result of the situation in which the gastric
emptying contractions are vigorous but must operate against a
contracted pyloric sphincter. These vigorous peristaltic
contractions eventually begin to force gastric contents to flow
retrograde into the esophagus because of the inherent imbalance
between a very strong pyloric sphincter and a much weaker
gastro-esophageal sphincter. The delay in gastric emptying is
directly related to a slow down in the transport of chyme out of
the ampulla and superior duodenum. The drugs used to treat this
disease raise pH further dampening the hydrogen-receptor-pancreatic
secretion loop, further delaying gastric emptying. Benini, "Gastric
Emptying and Dyspeptic Symptoms in Patients with Gastroesophageal
Reflux", Amer. J. of Gastroenterology, pp. 1351-1354 (1996).
[0028] The present invention is directed towards reestablishing the
link between gastric emptying and pancreatic secretion delivery,
thereby addressing the main pathology of this disease by shortening
chyme residence time in the superior duodenum so that intestinal
contents move into the distal digestive tract in a more normal
manner. According to a first embodiment, this is done by
stimulating the H+ ion receptors or by stimulation of the pancreas
directly or via its parasympathetic innervation (pre-ganglionic
Vagal nerves). Stimulation of pancreatic exocrine secretion has
been shown by direct stimulation of the thoracic vagus nerves in
dogs. Kaminski et al., "The Effect of Electrical Vagal Stimulation
on Canine Pancreatic Exocrine Function", Surgery, pp. 545-552
(1975). This results in a more rapid (normal) neutralization of
chyme in the ampulla, allowing it move down the duodenum more
quickly so that gastric emptying is returned to a more normal
pace.
[0029] Acidity (pH) can be assessed by measuring bicarbonate. It
will be understood that references to -H includes such indirect
measurements. Also, effects of the therapy described herein can be
assessed and/or controlled by measuring an indication of pancreatic
exocrine secretion or bile (e.g., HCO.sub.3.sup.-).
[0030] An alternative embodiment uses gastrocopic delivery of a
paralyzing agent (e.g. botulism toxin) to the pyloric valve along
with use of H.sub.2 antagonists or PPI's to manage the acidity of
the chyme reaching the duodenum.
[0031] As an additional alternative to pancreatic stimulation, the
gall bladder can be stimulated to encourage bile movement into the
duodenum. Shown schematically in the figures, the gall bladder GB
resides below the liver L. The gall bladder is connected to the
small intestine (specifically the duodenum D) via a bile duct BD.
The bile duct BD can discharge directly into the duodenum D or via
the pancreatic duct PD as shown. The bile can normalize the chyme
to accelerate duodenal emptying. Bile consists of bile acids
(detergents that emulsify lipids), cholesterol, phospholipids,
electrolytes such as (Na.sup.+, K.sup.+, Ca.sup.+2, Cl.sup.-,
HCO.sub.3.sup.') and H.sub.2O. Chapter 4, "The Liver and Biliary
Tract", Gastrointestinal System, 2.sup.nd Ed., M. S. Long editor,
Mosby Publisher, London (2002). The gall bladder GB or bile duct
can be stimulated indirectly via stimulation of the vagal nerve VN
or directly stimulated by an electrode or other stimulator.
[0032] As illustrated in the figures, an electrical stimulator 10,
20 which may be implanted is provided which alternatively may be
directly connected to the Vagal nerve VN (e.g., via stimulation
pathway 13) or the pancreas P (e.g., via stimulation pathway 111
shown in dashed line) to stimulate the pancreas directly or
indirectly to excrete exocrine into the duodenum D (or more
distally into the small intestine--e.g., into the jejunum) and
increase the pH of chyme in the duodenum D as described.
Alternatively, the same can be done to promote bile release by
stimulating the bile duct BD or the gall bladder GB either directly
(e.g., via stimulation pathway 11) or indirectly (e.g., by
stimulating Vagal nerve VN via stimulation pathway 13). In other
embodiments, the duodenum D can be stimulated directly (e.g., via
one or more electrodes or other stimulators as indicated by pathway
11) to cause propulsive contractions that accelerate duodenum
emptying. The frequency may be varied to maximize the response and
selectively stimulate exocrine instead of endocrine secretions.
Rosch et al., "Frequency-Dependent Secretion of Pancreatic Amylase,
Lipase, Trypsin, and Chymotrypsin During Vagal Stimulation in
Rats", Pancreas, pp. 499-506 (1990). See, also, Berthoud et al.,
"Characteristics of Gastric and Pancreatic Reponses to Vagal
Stimulation with Varied Frequencies: Evidence for Different Fiber
Calibers?", J. Auto. Nervous Sys., pp. 77-84 (1987) (showed
frequency-response relationship with insulin, i.e., significantly
less insulin was released at lower frequencies -2 Hz v. 8 Hz--also,
frequency-response curves evidenced distinctly different profiles
for gastric, pancreatic and cardiovascular responses.) Slight
insulin release can maximize pancreatic exocrine secretion. Chey et
al., "Neural Hormonal Regulation of Exocrine Pancreatic Secretion",
Pancreatology, pp. 320-335 (2001).
[0033] With a patient control stimulation as shown in FIG. 1, the
patient may activate the stimulator 10 by remote transmitter to
stimulate an electrical charge either after eating (e.g., about 60
to 90 minutes after eating) or on onset of GERD symptoms. It will
be appreciated that there are a wide variety of nerve stimulators
and organ stimulators available for implantation and are
commercially available and which include connectors for connecting
directly to nerves.
[0034] FIG. 2 illustrates an additional embodiment where the
patient activated loop is replaced with an automatic loop having a
programmable stimulator 20 which receives as an input signals from
sensors in the duodenum to measure pH, osmolality or strain (e.g.,
from baro-sensors) on the duodenum indicating filling or may
measure acidity in the esophagus or strain on the lower esophageal
sphincter LES or stomach S all of which may be provided to the
implantable controller 20 which can be provided with desirable
software to process the incoming signals and generate a stimulating
signal to either the Vagal nerve, the pancreas P, the gall bladder
GB, the bile duct BD or the duodenum D (or jejunum) directly in
response to such received signals. It will be appreciated that
stimulators and controllers are well within the skill of the art.
U.S. Pat. No. 5,540,730, which is hereby incorporated by reference
in its entirety, teaches a neurostimulator to stimulate a vagus
nerve to treat a motility disorder. U.S. Pat. No. 5,292,344, which
is hereby incorporated by reference in its entirety, teaches
gastrointestinal sensors including pH sensors.
[0035] With the foregoing detailed description of the present
invention, it has been shown how the objects of the invention have
been attained in a preferred manner. Modifications and equivalents
of disclosed concepts such as those which might readily occur to
one skilled in the art, are intended to be included in the scope of
the claims which are appended hereto.
* * * * *