Clinical trial NCT01574339: Effect of Long-Term Electrical Stimulation on LES Pressure and Esophageal Acid Exposure in Patients With GERD
Official title: An Investigation of the Effect of Long-Term Electrical Stimulation on Lower Esophageal Sphincter (LES) Pressure and Esophageal Acid Exposure in Patients With Gastroesophageal Reflux Disease (GERD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastroesophageal Reflux Disease
Keywords: GERD
LES Pressure
Electrical Stimulation
Lead sponsor: EndoStim Inc.
Sponsor class: INDUSTRY
First posted: 2012-04-10
Enrollment: 42
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All enrolled subjects will receive a functioning device and have stimulation delivered throughout the study.
Primary purpose: TREATMENT

Brief summary: The EndoStim LES Stimulation System is an investigational device intended to improve the LES pressure and restore Lower Esophageal Sphincter (LES) function in individuals suffering from Gastroesophageal Reflux Disease (GERD).

Detailed description: EndoStim has developed an investigational medical device specifically designed to deliver electrical stimulation to the LES and has completed two clinical feasibility studies using an external version of the EndoStim stimulation system in fifteen subjects. In these two short-term studies, electrical stimulation resulted in significant increases in LES pressure.

This study will further evaluate the safety of the procedure and its feasibility for use in this group of patients.

Eligibility criteria: Inclusion Criteria:

* Subject is between 21 - 70 years of age.
* Subject has a history of heartburn, regurgitation or both for \> 12 month prompting physician recommendation of continual daily use of PPI before study entry.
* Baseline GERD HRQL heartburn score following 10-14 days off PPI which is ≥ 20 and at least 10 points higher than the on PPI score
* Subject who are on standard medical therapy for 12 months or longer and experience discomfort or who are otherwise dissatisfied with GERD symptoms
* Subjects with a GERD condition that in the opinion of the PI justifies a minimally invasive reversible procedure prior to attempting anatomical change such as Nissen fundoplication
* Subject has an American Society of Anesthesiologists (ASA) Physical Status Classification I or II (or comparable local classification if any).
* Subject has exhibited excessive lower esophageal acid exposure during 24-hour pHmetry of antisecretory therapy performed within 6 months of screening visit; pH \< 4 for \> 5% of total time.
* Subject has a resting LES end expiratory pressure \> 5mm Hg and \< 15 mm Hg on a high resolution manometry within 6 months of enrollment.
* Subject has esophagitis ≤ Grade C (LA classification) on upper endoscopy within 6 months of enrollment.
* Subject has esophageal body contraction amplitude \> 30 mmHg for \> 50% of swallows and \> 50% peristaltic contractions on high resolution manometry.
* Subject has signed the informed consent form and is able to adhere to study visit schedule.

Exclusion Criteria:

* Subject has any non-GERD esophageal motility disorders.
* Subject has gastroparesis.
* Subject has any significant multisystem diseases.
* Subject has an autoimmune or a connective tissue disorder (e.g. scleroderma, dermatomyositis, Calcinosis-Raynaud's-Esophagus, Sclerodactyly Syndrome (CREST), Sjogren's Syndrome, Sharp's Syndrome), requiring therapy in the preceding 2 years.
* Subject has Barrett's epithelium (\> M2; \> C1) or any grade of dysplasia.
* Subject has a hiatal hernia larger than 3 cm.
* Subject has a body mass index (BMI) greater than 35 kg/m2.
* Subject has Type 1 diabetes mellitus
* Subject has uncontrolled Type 2 diabetes mellitus (T2DM) defined as HbA1c \> 9.5 in the previous 6 months, or has T2DM for \> 10 years.
* Subject has a history of suspected or confirmed esophageal or gastric cancer.
* Subject has esophageal or gastric varices.
* Subject has significant cardiac arrhythmia or ectopy or significant cardiovascular disease.
* Subject has an existing implanted electrical stimulator (e.g., pacemaker, AICD).
* Subject requires chronic anticoagulant therapy.
* Subject has dysphagia or esophageal peptic stricture, excluding Schatzki's ring.
* Subject of child-bearing potential who is pregnant or intends to become pregnant during the trial period.
* Subject is currently enrolled in other potentially confounding research.
* History of any malignancy in the last 2 years.
* History of previous esophageal or gastric surgery, including nissen fundoplication.
* Subject has any condition that, at the discretion of the investigator or sponsor, would preclude participation in the trial.

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: 24 months
Secondary outcomes:
measure: Change in GERD-HRQL
timeFrame: Change in GERD-HRQL and RDQ questionnaire score when available from baseline (as measured off PPI) to 1, 3, 6, 12, 18 and 24 months. Heartburn and regurgitation scores will be calculated separately.
measure: Change in GERD symptoms
timeFrame: Changes in GERD symptoms as measured by the SF-12 questionnaire will be compared between baseline assessments and post-implant measures at 6, 12, and 24 months.
measure: Change in GERD symptoms
timeFrame: Changes in GERD symptoms as measured by the patient daily symptom-diary at 3, 6, 12, 18 and 24 months Vs. baseline.
measure: Change in LES pressure
timeFrame: Baseline LES end expiratory pressure (LESPpre) will be compared with the end expiratory pressure (LESPpost) at 3 and 6 months.
measure: Change in GI symptoms
timeFrame: Symptoms will be compared between baseline (as measured while on and off PPI) to 1, 3, 6, 12, 18 and 24 months.
measure: Change in esophageal acid exposure
timeFrame: pH will be compared between baseline and 3, 6, 12 and 24 months.
measure: Change in esophageal acid exposure
timeFrame: Number of reflux events >1 minute will be compared between baseline and 3, 6, 12 and 24 months.
measure: Change in esophageal acid exposure
timeFrame: Number of reflux events >5 minutes will be compared between baseline and 3, 6, 12 and 24 months.
measure: Change in medication usage
timeFrame: The use of antisecretory medication will be compared between baseline and 3, 6, 12, 18 and 24 months.
measure: Change in sleep-related quality of life
timeFrame: Baseline and 6, 12, and 24 months scores of Sleep quality questionnaire.
measure: Change in work productivity
timeFrame: Baseline and 6, 12, and 24 months scores of Sleep quality and Work productivity questionnaires
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Hospital Clinico de la Pontificia Universidad Catolica de Chile
city: Bogota
country: Colombia
facility: San Ignacio
city: Hong Kong
country: Hong Kong
facility: Chinese University of Hong Kong (CUHK) / Prince of Whales
city: Hyderabad
country: India
facility: Asian Institute of Gastroenterology
city: Mexico City
country: Mexico
facility: . Zalvador Zubiran National Institute of Medical Science and Nutrition
city: Amsterdam
country: Netherlands
facility: AMC Amsterdam
city: Maastricht
country: Netherlands
facility: UMC Maastrcht
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Auckland
country: New Zealand
facility: North Shore Hospital
state: Takapuna
city: London
country: United Kingdom
facility: St. Thomas Hospital
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: A. J. Bredenoord, Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Stadtkrankenhaus Schwabach, Schwabach, Germany
name: T. Horbach, PD. Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinico de la Pontificia Universidad Catolica de Chile, Santiago, Chile
name: A. Escalona, Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Asian Institute of Gastroenterology
name: Nageshwar Reddy, M.D.,
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sidhu AS, Triadafilopoulos G. Neuro-regulation of lower esophageal sphincter function as treatment for gastroesophageal reflux disease. World J Gastroenterol. 2008 Feb 21;14(7):985-90. doi: 10.3748/wjg.14.985.
citation: Sanmiguel CP, Hagiike M, Mintchev MP, Cruz RD, Phillips EH, Cunneen SA, Conklin JL, Soffer EE. Effect of electrical stimulation of the LES on LES pressure in a canine model. Am J Physiol Gastrointest Liver Physiol. 2008 Aug;295(2):G389-94. doi: 10.1152/ajpgi.90201.2008.
citation: Kappelle WF, Bredenoord AJ, Conchillo JM, Ruurda JP, Bouvy ND, van Berge Henegouwen MI, Chiu PW, Booth M, Hani A, Reddy DN, Bogte A, Smout AJ, Wu JC, Escalona A, Valdovinos MA, Torres-Villalobos G, Siersema PD. Electrical stimulation therapy of the lower oesophageal sphincter for refractory gastro-oesophageal reflux disease - interim results of an international multicentre trial. Aliment Pharmacol Ther. 2015 Sep;42(5):614-25. doi: 10.1111/apt.13306. Epub 2015 Jul 8.