Effect of Long-Term Electrical Stimulation on LES Pressure and Esophageal Acid Exposure in Patients With GERD

• ClinicalTrials.gov Identifier: NCT01574339
• Recruitment Status: Unknown
• First Posted: April 10, 2012
• Last Update Posted: March 18, 2015
• Sponsor: EndoStim Inc.
• Information provided by (Responsible Party): EndoStim Inc.

Tracking Information

• First Submitted Date: March 22, 2012
• First Posted Date: April 10, 2012
• Last Update Posted Date: March 18, 2015
• Study Start Date: August 2011
• Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 8, 2012)

Primary Safety Endpoint [ Time Frame: 6 months follow-up ]

Safety will be assessed by incidence and severity of adverse events through 6 months follow-up. Included in this assessment will be the proportion of subjects with any of the following outcomes between device implant and completion of the month 6 evaluation: (1) death, or (2) medical morbidity associated with the device and/or implantation procedure.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 8, 2012)

• Secondary Efficacy Endpoints [ Time Frame: 6 months follow-up ]
  Change in patient's GERD-HRQL from baseline to 6 months.
• Secondary Efficacy Endpoints [ Time Frame: 6 months follow-up ]
  Baseline pH values of % 24-hour esophageal pH< 4.0, and number of reflux events >1minute and >5 minute duration with the same on-stimulation pH parameters at 6 months.
• Secondary Efficacy Endpoints [ Time Frame: 6 months follow-up ]
  Change in symptoms frequency and severity at 6 months Vs. baseline as measured by patient symptom diary and patients quality of life measured by SF- 12.
• Secondary Efficacy Endpoints [ Time Frame: 6 months follow-up ]
  Change in antisecretory medication use as evaluated during the two weeks prior to the month 6 follow up compared to baseline.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gastroesophageal Reflux Disease

Intervention

Device: EndoStim LES Stimulation System

The EndoStim LES Stimulation System comprises three components: an electrical stimulation lead, an implantable pulse generator (IPG) and an external programmer.

The IPG and stimulation lead are to be implanted within the subject's body using conventional laparoscopy. The device programmer is to be used by the study investigator and/or a company technical representative.

Study Arms

Experimental: Treatment Arm

Intervention: Device: EndoStim LES Stimulation System

• Publications *: 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.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: March 17, 2015): 42
• Original Estimated Enrollment (submitted: April 8, 2012): 30
• Estimated Study Completion Date: July 2016
• Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Chile, Colombia, India, Mexico, Netherlands, New Zealand, United Kingdom
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT01574339
• Other Study ID Numbers: CS005
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: EndoStim Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: EndoStim Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: A. J. Bredenoord, Dr. med.; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Principal Investigator: T. Horbach, PD. Dr. med.; Stadtkrankenhaus Schwabach, Schwabach, Germany
• Principal Investigator: A. Escalona, Dr. med.; Hospital Clinico de la Pontificia Universidad Catolica de Chile, Santiago, Chile
• Principal Investigator: Nageshwar Reddy, M.D.,; Asian Institute of Gastroenterology

• PRS Account: EndoStim Inc.
• Verification Date: March 2015