Transoral Incisionless Fundoplication (TIF) for Laryngopharyngeal Reflux (LPR) Patients

Study Overview
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Brief Summary
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In this research study the investigators want to learn more about the effectiveness of an endoscopic procedure (an endoscope is a lighted tube that is placed down the participants esophagus, through the participants mouth) which uses a device that allows the doctor to repair or recreate the body's natural barrier to reflux. It uses preloaded forceps (tweezers) and fasteners and requires no incision to tighten the connection between the participants esophagus and stomach. This procedure is performed to aid in the treatment of symptoms of Gastroesophageal Reflux disease (GERD) in patients with diagnosed Laryngopharyngeal reflux (LPR). LPR is a condition resulting from backflow of stomach contents into the laryngopharynx (connection point in the participants throat through which food, water, and air pass) resulting in symptoms that can be referred to larynx/hypopharynx. The device the investigators will use to perform the transoral incisionless fundoplication procedure (TIF) is called the EsophyX device. The participants have been asked to participate because they have been diagnosed with LPR and have either failed medical therapy (taking prescription proton pump inhibitors (PPI) to reduce stomach acid production or do not want to be on long-term medical treatment.

Detailed Description
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To date, more than one-third of the motility patients that the investigators see in practice at Brigham and Women's Hospital have LPR. There is currently limited literature available addressing LPR as a primary indication for the TIF procedure moreover there is no single therapy that has proved its efficacy over the years against LPR. The investigators propose a pilot study to investigate the efficacy of TIF with the EsophyX device (EndoGastric Solutions, Inc., Redmond WA, USA) in patients with LPR. The study design would include up to 25 patients to receive the TIF procedure and will take 12 months to complete it. The investigators will compare objective and subjective outcomes at baseline and 3 months post TIF procedure to assess its efficacy against LPR. The investigators will submit the proposal to EndoGastric solutions, anticipating that they will cover part of the funding required to conduct our Pilot Study. In conclusion, LPR lacks an effective therapy despite posing a significant healthcare burden. Medical therapy with PPI has a variable response, and more invasive Laparoscopic fundoplication is associated with a high risk of unwanted long-term side effects. TIF can potentially bridge this gap between medical and more invasive approaches for the patient population suffering from this condition. It has the potential to prove to be a less invasive and safe treatment indication for patients with chronic or refractory LPR who have either failed medical therapy or do not want to be on long-term medical treatment.

Official Title
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Transoral Incisionless Fundoplication (TIF) for Laryngopharyngeal Reflux (LPR) Patients

Conditions
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Motility Disorder, Gastroesophageal Reflux Disease (GERD), Laryngopharyngeal Reflux (LPR), Reflux Disease, Gastro-Esophageal

Intervention / Treatment
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* Device: Transoral Incisionless Fundoplication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any adult with a confirmed diagnosis of LPR with HEMII-pH (≥2 LPR events in 24 hr period), Esophageal manometry and Laryngoscopy. Having daily bothersome symptoms of LPR. Willing and able to cognitively sign a consent form for Surgical treatment of LPR with the TIF. Willing and available for follow up visit and repeat testing (HEMII-pH, Esophageal manometry and laryngoscopy) at 3 months post procedure. Exclusion Criteria: Unable or unwilling to provide informed consent Unable or unwilling to comply with study procedures Body Mass Index >35. Hiatal hernia>2cm in axial height and >2cm in greatest transverse dimension. Esophagitis grade C and D Barrett's esophagus>2cm Esophageal ulcer Fixed esophageal stricture or narrowing Portal hypertension and/or varices Active gastro-duodenal ulcer disease; Gastric outlet obstruction or stenosis Gastroparesis Coagulation disorders History of any of the following: resective gastric or esophageal surgery, anti-reflux surgery with anatomy unsuitable for TIF procedure per physician judgment, cervical spine fusion, Zenker's diverticulum, esophageal epiphrenic diverticulum, achalasia, scleroderma or dermatomyositis, eosinophilic esophagitis, or cirrhosis Pregnancy or plans of pregnancy in the next 12 months Enrollment in another device or drug study that may confound the results. Acute or chronic illness or history of illness which in the opinion of the investigator could pose a threat or harm to the subject or obscure interpretation of laboratory test results or interpretation of study data, such as frequent angina, Class III or IV congestive heart failure, moderate impairment of renal or hepatic function, poorly controlled diabetes (HbA1c >12%), etc. Any clinically significant abnormalities on physical examination or laboratory abnormalities identified in the medical record, as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LPR Patients<br>Adults with a confirmed diagnosis of LPR with HEMII-pH (≥2 LPR events in 24 hr period), Esophageal manometry and Laryngoscopy undergoing endoscopic transoral incisionless fundoplication (TIF). | Device: Transoral Incisionless Fundoplication<br>* Transoral incisionless fundoplication (TIF) is a minimally invasive, endoscopic fundoplication technique. Transoral Incisionless Fundoplication (TIF) is an FDA approved endoluminal fundoplication technique which utilizes EsophyX device to restore the valve at the gastroesophageal junction. The EsophyX device (EndoGastric Solutions, Redmond, Wash, USA) is an FDA approved procedure for chronic of refractory GERD.<br>* Other names: TIF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LPR Symptoms | Number of participants reporting LPR symptom elimination or clinically significant improvement evaluated by RSI (Reflux Symptom Index) and GERD-HRQL Questionnaire. | Baseline and 3 months post-procedure | 
| LPR Events | Number of participants with reduced LPR events as evaluated by HEMII-pH | Baseline and 3 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GERD Symptoms | Elimination of Daily bothersome GERD symptoms evaluated by GERD-HRQL Questionnaire | Baseline and 3 months post-procedure | 
| Patient Satisfaction | Patients Satisfaction evaluated by GERD-HRQL Questionnaire | Baseline and 3 months post-procedure | 
| Lower Esophageal Sphincter Tone | Change in Lower esophageal sphincter tone evaluated by Esophageal manometry | Baseline and 3 months post-procedure | 
| Laryngopharyngeal anatomy | Change in Laryngopharyngeal anatomy evaluated by Laryngoscopy | Baseline and 3 months post-procedure | 
| PPI Discontinuation | Discontinuation of PPI's | Baseline and 3 months post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GERD-HRQL, Transoral Incisionless Fundoplication (TIF), Fundoplication, Nissen Fundoplication, Proton Pump Inhibitor, Esophageal Manometry, Laryngoscopy, HEMII-pH, Reflux Symptom Index (RSI)