Nocturnal Reflux White Paper

Now and Future: GERD
and Nocturnal Acid
Reflux Treatments
Aaron M. Clark
Amenity Health, Inc.
EXECUTIVE SUMMARY
With at least 10% of the US population suffering from gastroesophageal reflux disease (GERD)
and the majority (89%) of this population also suffering from nocturnal acid reflux, the treatment
of GERD and nocturnal acid reflux has become a major topic of discussion for the medical
community at large.
The dangers posed specifically by nocturnal acid reflux are particularly significant as prolonged
esophageal acid exposure has been linked to leading to serious health complications, such as erosive
esophagitis, peptic stricture, esophageal ulcerations, Barrett’s esophagus, and adenocarcinoma
of the esophagus. Additionally, patients who suffer from nocturnal acid reflux experience a
diminished health-related quality of life as sleep deprivation takes its toll health-wise and on
productivity in the workplace.
The current treatment options for GERD and nocturnal acid reflux include lifestyle changes,
medications, and surgery. While lifestyle changes are recommended, Proton Pump Inhibitor (PPI)
medications, have become the mainstay of treatment. However, this class of medication has been
linked by the FDA with serious health risks. Surgical procedures are often ineffective at providing
desired symptom relief and come with negative side effects.
Amenity Health developed the Medcline reflux relief system to address this need for nocturnal
acid reflux patients. Validated by a clinical study at the Medical University of South Carolina,
sleeping on Medcline has been proven to decrease patient esophageal acid exposure without the
side effects posed by PPIs and surgery.
TM
TM
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Now and Future: GERD and Nocturnal Acid Reflux Treatments
SYMPTOMS OF GERD AND
NOCTURNAL ACID REFLUX
At least 10% of Americans have been diagnosed with gastroesophageal reflux disease (GERD)1. While the most common
complaints from those suffering from GERD are of heartburn
and acid reflux, there are many less obvious symptoms such
as dysphagia (difficulty swallowing), chronic cough, asthma,
hoarseness, laryngitis, chronic sinusitis, headaches, and dental
erosions2. Symptoms are produced by the abnormal reflux of
gastric contents (stomach acid) from the stomach back up into
the esophagus3.
The majority of GERD sufferers also experience nocturnal
acid reflux. In fact, in a survey of 11,685 survey respondents
with GERD, 88.9% experienced nighttime symptoms, 68.3%
experienced sleep difficulties, 49.1% experienced difficulty
initiating sleep, and 58.2% experienced difficulty maintaining
sleep4. Symptoms specific to nocturnal acid reflux, include
nighttime awakenings caused by coughing or choking,
regurgitation of fluid or food, and an acidic/bitter taste.
DANGERS SPECIFIC TO NOCTURNAL ACID
REFLUX
Increased Esophageal Exposure
During sleep, the body’s natural defense mechanisms against
refluxed stomach contents, including saliva production and
swallowing, are greatly reduced5. Also, during the night,
though reflux episodes tend to be less frequent than during
the day, nighttime episodes are longer in duration6. Both of
these factors lead to increased nighttime acid exposure making
nocturnal acid reflux, in fact, more serious than daytime acid
reflux7.
Nocturnal acid reflux has been found to be an underlying risk
factor for developing more serious health complications, such
as erosive esophagitis, peptic stricture, esophageal ulcerations,
Barrett’s esophagus, and adenocarcinoma of the esophagus8.
In fact, while the risk of esophageal adenocarcinoma
increases eightfold for those suffering with daytime acid
reflux symptoms, the risk increases to 11-fold for those with
nighttime symptoms9. Esophageal adenocarcinoma is actually
the fastest growing cancer in terms of incidence in the United
States10.
Diminished Health-Related Quality of Life
Beyond esophageal damage, nighttime symptoms are very
disruptive to sleep, often leading to sleep deprivation. Over
time, sleep deprivation takes its toll resulting in a substantially
diminished health-related quality of life as compared to those
without nighttime symptoms11 .
Sleep deprivation causes difficulties in concentration; vision
disturbances; slower reaction times; lower capabilities and
efficiency of task performance; increased number of errors;
and slurred speech. Longer–term health consequences
include increased sensitivity to pain; changes in the immune
response and hormonal secretion patterns; increased risk of
obesity; diabetes; and increases in cardiovascular disease12. The
treatment of GERD itself and the secondary consequences of
nighttime symptoms as related to sleep deprivation result in a
marked economic burden on the healthcare system13.
• 30 million in US suffer from GERD
• 88.9% experience nighttime symptoms
• $75 billion in lost productivity each year
Lost Productive Time
There are also significant indirect costs to nocturnal acid reflux
and GERD in terms of lost productive time. A 2005 study
found a 10% reduction in productivity caused by nighttime
symptoms and the resultant sleep deprivation. When
extrapolated based on 2005 salary data, the study found that
based on the estimated 14.5 million people of working age
with GERD in the US, this 10% reduction in productivity
costs US employers up to $75 billion/year14.
TREATMENT OPTIONS
Currently within the medical community, there are three main
treatment protocols for nocturnal acid reflux and GERD.
Treatment aims to relieve symptoms, improve patient healthrelated quality of life, and reduce the potential for developing
serious complications from chronic damage to the esophagus.
Current treatments include one or more of the following: (a)
lifestyle changes, including changes to diet, weight loss, and
sleep positioning; (b) medications, including antacids, H2
blockers, PPIs; and/or (c) surgical procedures.
Lifestyle Changes
Diet and Weight Loss
When diagnosing GERD, many doctors will first look at
a patient’s diet to determine if there are any changes that
can be made to decrease symptoms. It has been found that
meals that are smaller and lower in fat tend to create less acid
exposure than meals that are larger and higher in fat15. It is
often recommended that patients avoid coffee, tea, carbonated
3
beverages, alcohol, citrus fruits, tomatoes, chocolate, mint or
peppermint, fatty or spicy foods, onions, and garlic. Because
individuals react so differently to food, patients are often asked
to pay attention to the foods that seem to trigger symptoms
and avoid them as much as possible. Weight loss is also
recommended as extra pressure around the abdomen increases
acid reflux.
Sleep Positioning
During sleep the body naturally produces less saliva and
swallowing decreases resulting in increased acid clearance time
in the esophagus5. Increased acid clearance time means that
refluxed stomach acid lingers in the esophagus potentially
causing serious erosion and long-term damage. Additionally,
when laying flat on the back at night (supine position) gravity
cannot help clear acid back to the stomach. Doctors often
recommend sleeping at an incline to help with acid clearance
time. Traditionally, there are two methods to sleep in an
inclined position – head of bed elevation (HOB) or sleeping
on a bed wedge.
HOB is typically achieved by putting blocks or risers under
the bed frame so that the entire head of the bed is elevated.
Studies have shown a reduction in nocturnal acid exposure,
acid clearance time, and symptom improvement16. Though
potentially effective, many who try HOB complain that sliding
down throughout the night is a consistent issue and/or their
sleep-mate is disturbed17.
Another traditional method of achieving elevated sleep
positioning is utilizing a bed wedge. Studies have shown that
while sleeping on a wedge does produce a decrease in distal
esophageal acid exposure, it does not decrease the number
of reflux episodes throughout the night17. Critics of this
technique site that wedges elevate only the head, rather than
the entire upper torso of the body, so it does not give any
advantage of gravity in clearing reflux and further may cause
neck pain18. As with HOB, patients also have a tendency to
slide down the wedge throughout the night.
Head of Bed Elevation (HOB)
Bed Wedge
In looking at both traditional methods, HOB and the use of
a bed wedge have been shown to provide similar, but limited,
levels of relief17.
4
Many studies have found that GERD patients are more
likely to reflux when lying flat on the right side and that
acid clearance time is slower when lying on the right side
so episodes last longer19. These findings suggest that GERD
patients should be advised to sleep on their left side to
decrease reflux episodes and the duration of those episodes.
Additionally, right-side episodes tend to be more distressing
and destructive as they are predominately liquid in nature20.
Medications
In addition to OTC antacids, there are two classes of
medications generally used to treat GERD, both of which act
to suppress gastric acid secretion - Proton Pump Inhibitors
(PPIs) and Histamine 2 Receptor Antagonist (H2 blockers).
Brand names for PPIs include Prilosec®(omeprazole),
Prevacid® (lansoprazole), AcipHex® (rabeprazole), Protonix®
(pantoprazole), Nexium® (esomeprazole); Zegarid®
(omeprazole). Brand names for H2 blockers include Tagamet®
(cimetidine), Pepcid® (famotidine), Axid® (nizatidine), and
Zantac® (ranitidine). Which medication, or combination
of medication used, varies based on severity and individual
response to each class of medication.
Antacids
OTC antacids, such as Tums® or Rolaids®, act to neutralize
acid in the esophagus but do not significantly alter overall
gastric pH levels21. Additionally, while antacids can provide
immediate symptom relief, they do not prevent subsequent
heartburn episodes and often offer short-lived relief.
Histamine 2 Receptor Antagonist (H2 blockers)
Histamine 2 Receptor Antagonist (H2 blockers) block the
action of histamine on acid producing cells, thus reducing
stomach acid production. H2 blockers have been found to
provide long-term symptom control in about 50% of GERD
patients, especially those with mild-to-moderate symptoms
and also promote esophageal healing in 44–58% of treated
patients22. H2 blockers are often prescribed to patients who
continue to be symptomatic on standard or double-dose
PPIs23. Also, over-the-counter H2 blockers are often used
as an on-demand solution because of their rapid effect on
symptoms1.
Though H2 blockers can provide symptom relief, tachyphylaxis
develops quickly, meaning that patients build up a resistance
over time so doses have to continue to increase. Patient’s built–
up resistance to H2 blockers limits their regular use in clinical
practice24.
Now and Future: GERD and Nocturnal Acid Reflux Treatments
Proton Pump Inhibitors (PPIs)
Proton pump inhibitors reduce the production of acid by
blocking the enzyme in the wall of the stomach that produces
acid. In 2009, more than 119 million PPI prescriptions were
written in the US. $13.5 billion is spent on PPIs in the US
annually, making them the second biggest-selling drug class
after cholesterol lowering agents25.
PPIs came onto the market in the 80s and quickly have
become the treatment of choice for GERD and nocturnal
Acid Reflux due to their profound and consistent inhibitory
effect on acid secretion1. Though PPIs do provide symptom
relief, they do not provide a long-term cure for GERD.
Additionally, recent population-based studies, along with
multiple FDA safety announcements, have suggested that
long-term PPI use may pose significant health risks to
patients.
As a result of the risks posed by long-term exposure to PPIs,
there is growing interest by patients and physicians alike to
discover non-PPI-related therapeutic strategies for GERD1.
Treating GERD with PPIs is also problematic in that up to
40% of those on a daily PPI are refractory, meaning they still
experience symptoms34.
Serious Health Complications with
Long-term PPI Use
•
Increased risk of contracting Clostridium Difficile, a
serious and potentially deadly bacterial infection26.
•
Increased risk of hip, wrist, and spine fractures with
high doses or long-term use of prescription PPIs27.
•
Possible connection to low serum magnesium levels
if taken for prolonged periods of time (in most
cases, longer than one year). In approximately onefourth of the cases reviewed, supplementation did
not improve low serum magnesium levels after the
PPI had to be discontinued28.
•
Possible cause of cardiovascular disease, which may
also increase the likelihood of a heart attack29.
•
Increased risk for vitamin B12 deficiency, which can
cause tiredness, weakness, constipation, and a loss
of appetite, and more seriously, balance problems,
memory difficulties, and nerve problems30.
•
Increased risk of developing community-acquired
pneumonia31.
•
Increased risk of acquiring microscopic colitis32
leading to chronic diarrhea.
•
Increased incidence of small intestinal bacterial
overgrowth (SIBO)33.
This ineffectiveness has also been found specifically in
nocturnal acid reflux patients as well. A survey of over 600
GERD patients on PPIs found that the majority of patients
continued to experience heartburn, with 83% experiencing
nocturnal symptoms and 32% reporting severe or very severe
nocturnal symptoms35. It has also been found that even when
doses of PPIs are increased, patients continue to experience
less than satisfactory symptomatic response36.
The estimated cost per person, per year of patients on a oncea-day PPI is $2,000 to $4,500 for brand name prescription
PPIs37.
Surgical Treatments for GERD
For patients who are unresponsive to lifestyle changes and
drug therapy, surgery is often explored. While other medical
procedures have been developed, such as Transoral Incisionless
Fundoplication (TIF), Radio-Frequency Ablation, and
Stretta® therapy, the most common surgery performed is
called Nissen Fundoplication.
Nissen Fundoplication
During this laparoscopic procedure, the surgeon wraps the
top part of the patient’s stomach around the lower part of
the esophagus attempting to tighten the lower esophagus to
prevent acid from refluxing from the stomach back into the
esophagus. The tightening of the lower esophagus, creating
what is often referred to as a “one way valve,” often leads to
unintended consequences. In fact, after the procedure, 60% of
patients developed new symptoms, such as dysphagia, choking,
epigastric pain, gas/bloating, inability to belch, nausea, and/or
diarrhea38.
Additionally problematic is that fact that follow up studies
have found that 40% of Nissen Fundoplication patients had
symptoms return, had esophagitis come back, needed medicine
for recurrent symptoms, and/or needed another operation after
seven years39.
The estimated cost of a Nissen Fundoplication procedure is
$18,000.
LINX® Reflux Management System
Another surgical option for patients who are unresponsive
to lifestyle changes and medications is the LINX® Reflux
Management System. The LINX® device (which consists of a
series of titanium beads, each with a magnetic core, connected
together with titanium wires to form a ring shape) is surgically
implanted around the lower end of the esophagus. The device
opens as food is digested down into the stomach, then tightens
up so that stomach contents cannot reflux back up into the
esophagus.
5
The average LINX® surgical procedure is $15,000 - $20,000.
AMENITY HEALTH OFFERS MEDCLINE™
TO TREAT NOCTURNAL ACID REFLUX
Medical research suggests that developing new therapeutic
strategies for GERD, in lieu of indefinite or high-dose PPI
treatments or invasive surgical procedures, should be a high
priority for pharmaceutical and medical device companies1.
Amenity Health developed Medcline™ to address this need.
Medcline™ is the much needed treatment alternative for
nocturnal acid reflux. The Medcline™ reflux relief system (see
Figure 1) leverages proven techniques for nighttime symptom
relief and protection against the serious health complications
associated with long-term esophageal acid exposure. Its
patented Cradle-Loc™ design places patients in an ideal
sleeping position with their entire torso elevated and gently
holds them on their left side for maximum results.
15-20˚
Figure 1: Medcline™ is comprised of an ergonomic incline base and
companion body pillow.
Under the direction of Donald O. Castell, MD, the Medical
University of South Carolina conducted a study to validate
the effectiveness of Medcline™. The study compared
Medcline™ to a traditional bed wedge and found that when
users slept on their left side, Medcline™ provides41:
• 87% reduction in esophageal acid exposure time
(see Figure 2)
• 38% reduction in nighttime acid reflux episodes
• 2x more comfort than a wedge
Medcline™ is a Class I Medical Device listed with the FDA
6
4%
3%
Percent Time pH < 4.0
The most common patient complaint following the LINX®
procedure include difficulty swallowing (76 events in 68
patients). The second most common complaint is pain (25
events in 24 patients)40. Additionally, patients who have the
LINX® device must not be exposed to, or undergo, Magnetic
Resonance Imaging (MRI) as this could cause serious injury to
the patient, as well as damage to the device.
2%
1%
0
Medcline™ Sleep
Assist Device
Bed Wedge
Figure 2: Medcline™ shows significantly less esophageal acid exposure
compared to a traditional bed wedge.
and cleared for patient use. Medcline™ also meets the IRS
Guidelines to be classified as an FSA/HSA-approved medical
expenditure. Patients can purchase Medcline™ directly from
Amenity Health.
Looking Ahead
Medcline™ is currently being utilized in a clinical study with
Cleveland Clinic. This study aims to quantify health-related
quality of life improvements when sleeping on Medcline™, as
well as accessing patients’ ability to decrease medication usage
over time.
In addition to patients with a GERD or nocturnal acid reflux
diagnosis, Amenity Health is continually researching new
applications for Medcline™, including thoracic patients for
lung transplants and idiopathic pulmonary fibrosis (IPF);
scleroderma patients; non-tuberculosis mycobacteria patients;
esophagectomy recovery patients; and silent reflux patients.
Now and Future: GERD and Nocturnal Acid Reflux Treatments
References
1 Hershcovici,Tiberiu, Fass, Ronnie. Gastro-oesophageal reflux disease,
beyond proton pump inhibitor therapy. Drugs 2011; 71 (18): 2381-2389.
2 Storr M, Meining A, Allescher HD. Pathophysiology and pharmacological
treatment of gastroesophageal reflux disease. Dig Dis Sci 2000; 18:
93–102.
3 DeVault, Kenneth R., Castell, Donald O. Updated guidelines for the
diagnosis and treatment of gastroesophageal reflux disease. American
Journal of Gastroenterology. 2005;100:190–200.
4 Mody, R., et al., Clinical Gastroenterol and Hepatol 2009;7:953-959.
5 Fass, Ronnie. PPI bashing’ drives use of alternatives. gastoendnews.com,
Sept. 2011.
6 Orr, WC, Johnson LF, Robinson MG. Effect of sleep on swallowing,
esophageal peristalsis, and acid clearance. Gastroenterology 1984; 86:
814-819.
7 Orr , William C., Management of nighttime gastroesophageal reflux disease,
Gastroenterology & Hepatology. 2007 August; 3(8): 605–606.
8 Lagergren, J, Bergstrom R, Lindgren A, et al. Sympomatic gastroesophageal
reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;
340: 825-831.
9 Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic GER
as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;
340:825–831.
10 Ashburn, Ted T, Gupta Meera S. The GERD market. Drug Discovery Vol .
5. April 2006. 277-278.
11 Farup, Kleinman, Sloan S, et al. The impact of nocturnal symptoms
associated with gastroesophageal reflux disease on health-related quality of
life. Arch Internal Med 2001; 161: 1448-1456.
12 Orzal-Gryglewska, Jolanta, Consequences of sleep deprivation.
International Journal of Occupational Medicine and Environmental
Health 2010; 23(1):95–114.
13 Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected
digestive diseases in the United States. Gastroenterology 2002 May; 122
(5): 1500-11.
14 Wahlqvist, P, Reilly ,MC, Barkun, A. Systematic review: the impact
of gastro-oesophageal reflux disease on work productivity, Aliment
Pharmacology & Therapeutics 24, 259–272.
15 Iwakiri et al., Dig Dis Sci 1996; 41:926.
16 Khan, Bashir A. et al. Journal of Gastroenterology and Hepatology,
Accepted article.
17 Hamilton, John W, et al. Sleeping on a wedge diminishes exposure of the
esophagus to refluxed acid. Digestive Diseases and Sciences, Vol. 33, No. 5
(May 1988), pp. 518-522.
18 Pope CE: Gastro esophageal reflux disease: Pathophysiology, diagnosis,
management. Philadelphia, WB Saunders 1983, 449-490.
19 Khoury, Ramez M. Influence of spontaneous sleep positions on nighttime
recumbent reflux in patients with Gastroesophageal Reflux Disease. The
American Journal of Gastroenterology. Vol. 94, No. 8, 1999.
20 Shay SS, Conwell DL, Mehindru V, et al. The effect of posture on
gastroesphageal reflux event frequency and composition during fasting.
Am J Gastroenterology. 1996; 91: 54-60.
21 McRorie JW Jr, Gibb RD, Miner PB Jr. Journal of American Assoc Nurse
Practice. 2014 May 13. doi: 10.1002/2327-6924.12133.
22 Galmiche JP, Letessier E, Scarpignato C. Treatment of gastro-oesophageal
reflux disease in adults. Br Med J 1998; 316:1720–1723.
23 Peghini PL, Katz PO, Castell, DO. Ranitidine controls nocturnal gastric
acid breakthrough on omeprazole: a controlled study in normal subjects.
Gastroenterology 1998; 115 (6): 1335-9.
24 Fackler WK, Ours TM, Vaezi MF, et al. Long-term effect of H2RA
therapy on nocturnal gastric acid breakthrough. Gastroenterology 2002;
122 (3): 625-32.
25 Heidelbaugh JJ, Goldberg KL, Inadomi JM. Overutilization of proton
pump inhibitors: a review of cost-effectiveness and risk[corrected] Am J
Gastroenterol. 2009;104 (Suppl 2):S27–S32.
26 Dial S, Alrasadi K,Manoukian C, et al. Risk of Clostridium difficile
diarrhea among hospital inpatients prescribed proton pump inhibitors:
cohort and case-control studies. CMAJ 2004 Jul 6; 171 (1): 33-8. AND
2.8.2012 FDA Safety Announcement.
27 Yang YX, Metz DC. Safety of proton pump inhibitor exposure.
Gastroenterology 2010 Oct; 139 (4): 1115-27 (and) 3.23.2011 FDA
Safety Announcement.
28 3.2.2011 FDA Safety Announcement.
29 Study conducted by researchers at Texas Methodist Hospital Research
Institute, Stanford University, and MRC Clinical Sciences Center,
Imperial College, London, UK, August 2013.
30 Study conducted by researchers at Kaiser Permanente, December 2013.
31 Laheij RJ, Sturkenboom MC, Hassing RJ, et al. Risk of communityacquired pneumonia and use of gastric acid suppressive drugs. JAMA 2004
Oct 27; 292 (16): 1955-60.
32 Keszthelyi D, Jansen SV, Schouten GA, et al. Proton pump inhibitor use
is associated with an increased risk for microscopic colitis: a case-control
study. Aliment Pharmacol Therapy. 2010 Nov; 32 (9): 1124-8.
33 Lombardo L, FotiM, Ruggia O, et al. Increased incidence of small
intestinal bacterial overgrowth during proton pump inhibitor therapy.
Clinical Gastroenterology & Hepatology 2010 Jun; 8 (6): 504-8.
34 Dickman, Ram, et al. Comparison of clinical characteristics of patients
with gastroesophageal reflux disease who failed proton pump inhibitor
therapy versus those who fully responded. J Neurogastroenterol Motil, Vol.
17 No. 4 October, 2011.
35 Chey WD , Mody RR , Wu EQ et al. Treatment patterns and symptom
control in patients with GERD: US community-based survey . Curr Med
Res Opin 2009 ; 25:1869–78.
36 Fass R, Murthy U, Hayden CW, et al. Omeprazole 40 mg once a day is
equally effective as lansoprazole 30 mg twice a day in symptom control of
patients with gastro-oesophageal reflux disease (GERD) who are resistant
to conventional-dose lansoprazole therapy-a prospective, randomized,
multi-centre study. Aliment Pharmacol Therapy 2000;14:1595-1603.
37 Monthly cost reflects nationwide retail average prices for March 2010,
rounded to the nearest dollar. Information derived by Consumer
Reports Best Buy Drugs from data provided by WoltersKluwer Health,
Pharmaceutical Audit Suite®. Average monthly cost is based on
recommended dosage of one pill daily. May, 2010.
38 Humphries, L.A., et al., Surg Endosc 2013;27:1537-1545.
39 Lundell, L. et al. (2007). Seven Year Follow-Up of a Randomized Clinical
Trial Comparing Proton-Pump Inhibition with Surgical Therapy for
Reflux Oesohpagitis. British Journal of Surgery, 94(2):198-203.
40 LINX™ Reflux Management System - P100049. http://www.
fda.gov/MedicalDevices/ProductsandMedicalProcedures/
DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm300790.
htm.
41 Person, EB, Rife CC, Castell DO, et al. A novel sleep-assist device
prevents gastroesophageal reflux: A randomized controlled trial. Am J
Gastroenterology 2013; 108:S1-S36.
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Copyright © 2014 Amenity Health, Inc. All rights reserved. Medcline™, and its affiliate brand names, is protected by US Patent No.8661586.
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