eletro stimulation of lower esophageal sphincter on gerd treatment
DESCRIPTION
First in man Studies in a novel, unique and disruptive technology to surgicaly treat Reflux desease (GERD) without anatomical changes by laparoscopic implant of leads on the esophagi-gastric junction (EGJ) followed by stimulation of a pace=makerTRANSCRIPT
Leonardo Rodriguez, MD, Chile
Manoel Galvao Neto, MD, Brazil
VK Sharma, MD,USA
Edy Soffer, MD, USA
Shai Policker, USA
Treatment of GERD
ELECTROSTIMULATION OFLOWER ESOPHAGEAL ESPHINCTER
GASTROESOPHAGEAL REFLUX DISEASE (GERD)
What is GERD (acid reflux)?
Reflux of gastric contents from the stomach into the esophagus
CausesHypotensive LESTransient LES
Relaxation (tLESR)
Lower Esophageal Sphincter Open Allowing for Reflux
Esophagus
Stomach
Pylorus
LES Sphincter Closed
Diaphragm
Liquid
Castell et al. American Journal of Gastroenterology, 2002; 97-575
GASTROESOPHAGEAL REFLUX DISEASE (GERD)
Treatment of GERDLife style modificationAntacids and H-2
Blockers, PPIsNissen Fundoplication
SurgeryRelatively invasiveCan require continued
medications1
Hard to convert
Castell et al. American Journal of Gastroenterology, 2002; 97-575
Lower Esophageal Sphincter Open Allowing for Reflux
Esophagus
Stomach
Pylorus
LES Sphincter Closed
Diaphragm
Liquid
GERD Is Common
GERD is a commonly diagnosed GI disorder1
Prevalence in Brazil is 12%4
The prevalence of GERD in the US is estimated at 30 million2
1. Richter JE. Gastroesophageal reflux disease and its complications. In: Feldman M et al, eds.Gastrointestinal and Liver Disease. 8th ed. Philadelphia, Pa: Saunders; 2006:905-936.
2. Sandler RS et al. Gastroenterology. 2002;122:1500-1511.3. US Census Bureau. State and County QuickFacts. 2008.4. GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF GASTROESOPHAGEAL
REFLUX DISEASE: an evidence-based consensus, Arq Gastroenterol, v. 47 – no.1 – jan./mar. 2010
Epidemiology
People With GERD million2
30
Population of New York City million3
8.2
People With Refractory GERD 10million2
Nearly 40% of Patients on Once-Daily PPI Therapy Have Breakthrough Symptoms
Patient-Reported Symptoms on Once-DailyPPI Therapy (N=1064)
Proton Pump Inhibitor (PPI) Failure
American Gastroenterological Association. GERD Patient Study: Patients and Their Medications. Harris Interactive Inc; 2008.
No Breakthrough Symptoms
62% Breakthrough Symptoms
38%
New Studies highlight negative effects of long-term PPI
ElectroStimulation of LES
ANIMAL STUDIESLaparoscopic (2008) / Endoscopic
(2007)
LES Electrical StimulationAnimal Studies
Effect of electrical stimulation of the LES on LES pressure
Canine model
Sanmiguel, et al (Cedar) AJPGI 2008
LES Electrical StimulationAnimal Studies
An endoscopically implantable device stimulates the LES
on demand by remote control:
a study using a canine model
Clarke, et al (Hopkins) Endoscopy 2007
ENDOSTIM NEUROSTIMULATOR TECHNOLOGY
ENDOSTIM NEUROSTIMULATOR TECHNOLOGY
ENDOSTIM NEUROSTIMULATOR TECHNOLOGY
ENDOSTIM NEUROSTIMULATOR TECHNOLOGY
Source: El Mercurio - Chile
ElectroStimulation of LES
FIRST IN MAN ACUTE STUDYAcute Proof of Concept Study (2010)
“Off response”
“On response”
“Off response”
“On response”
How smooth muscle cells works in esophagus…..
ElectroStimulation of LES
FIRST IN MAN CHRONIC STUDYOpen Label Study (2011)
Twenty-four patients treated for 6m or longer
Primary Endpoints:
Safety: No device related AE
Functionality: 100% detection of supine and treatment delivery
Secondary Endpoints:
Clinically significant improvement in all parameters: LES pressure and esophageal function (evaluated using HRM) Esophageal acid exposure Esophagitis healing GERD HRQL / patient symptoms PPI usage
CE-Mark Study ResultsSingle Arm, Treatment only protocol
ENDOSTIM IMPLANT
ENDOSTIM IMPLANT
ENDOSTIM IMPLANT
Clinically Significant Increase in LES Pressure
* p<0.005 compared to baseline
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
0 12
N=24 *
N=24
Baseline Month 3
End Exp.
Pressure
mmHg
SUSTAINED INCREASE OF LES PRESSURE
CONFIDENTIAL
v. Interim results, not fully monitored
Time Post Implant (weeks)
SUSTAINED ENHANCEMENT IN LES PRESSURE
PRESERVED SWALLOW FUNCTION
Baseline On Treatment
SUSTAINED DECREASE IN ESOPHAGEAL ACID EXPOSURE
CONFIDENTIAL
p<0.001 vs. baseline (n=23)pH Analysis Results Following Blinded Audit Performed by an Independent Expert Reviewer
SUSTAINED DECREASE IN ESOPHAGEAL ACID EXPOSURE
CONFIDENTIAL
p<0.001 vs. baseline (n=23)pH Analysis Results Following Blinded Audit Performed by an Independent Expert Reviewer
24-h Esophageal Acid Exposure
Baseline % 24h pH<4.0 =13.8%
12 Weeks % 24h pH<4.0 =0.7%
CONFIDENTIAL
Sustained Improvement in symptoms
* Interim data not fully monitored.
Results at each time point are given as mean ± SE * p<0.001 vs. baseline; n=24 † p<0.005 vs. week 4, n=23
* †****
*
On PPI BaselineOff PPI Baseline
* Interim data not fully monitored.
Results at each time point are given as mean ± SE * p<0.001 vs. baseline; n=24 † p<0.005 vs. week 4, n=23
REDUCTION of REFLUX EVENTS
CONFIDENTIAL
55% reduction in the number of total reflux events52% drop in the number of long events (>5min), 57% drop in number of short events
All results are highly statistically significant (p<0.001)
* Interim data not fully monitored.
Clinically Significant Healing of Esophagitis
ElectroStimulation of LES
1 YEAR CHRONIC STUDYOpen Label Study (2012)
Lap Fundoplication
Endoscopic Stim
Lap Stim
Invasiveness
Leonardo Rodriguez, MD, Chile
VK Sharma, MD,USA
Edy Soffer, MD, USA
Shai Poliker, USA
Manoel Galvao Neto, MD, Brazil
Treatment of GERD
ELECTROSTIMULATION OFLOWER ESOPHAGEAL ESPHINCTER