The Mechanism Versus PPI Trial

This research study is being conducted to compare the efficacy between usual care and a novel mechanism guided strategy for adults with chronic throat (laryngeal) symptoms undergoing evaluation for laryngopharyngeal reflux (LPR).

Usual care strategy is used clinically and is known to reduce chronic throat symptoms. The mechanism guided strategy is a new treatment that personalizes the application of acid suppression medication and voice therapy to the patient. The mechanism guided strategy is being evaluated for how well it works in patients with these throat symptoms.

Participants who are undergoing clinical evaluation for laryngopharyngeal reflux (LPR) inclusive of an upper endoscopy with ambulatory pH monitoring (reflux testing) will be recruited for participation in this study.

Participants will undergo screening to confirm eligibility. Once informed consent is administered and signed, participants will be asked about their demographic background, current symptoms, brief medical history, and current medications. Screening takes place within 30 days of a participant's scheduled clinical upper endoscopy with reflux testing.

After completing the clinical upper endoscopy and reflux testing, they will be scheduled for their first intervention visit, about 1 week later.

Participants will be randomized to 1 of 2 arms with of the study: 1) Mechanism Guided Strategy or 2) Usual Care Strategy. Randomization is 1:1 based on permuted block randomization in REDCap to mechanism guided or usual care strategy with stratification by concomitant esophageal + laryngeal symptoms versus isolated laryngeal symptoms.

Participants will then attend 3 in person treatment visits at UC San Diego Health's Research Clinic.

Participants will undergo measures at these visits included: 1) acoustics, 2) aerodynamics, 3) patient reported outcomes measuring symptom burden and quality of life, 4) Fasting saliva samples for pepsin and bile acid analysis, and 5) physiologic measures. The study team will also collect height, weight, current medications, and adverse events. Participants will be dispensed an oral capsule (omeprazole 40mg or placebo) based on their randomly assigned strategy. The participants in the mechanism guided strategy will receive omeprazole 40mg daily if their clinical upper endoscopy and reflux testing are conclusive with GERD. They will receive placebo if their upper endoscopy and reflux testing are not conclusive with GERD. The participants in the usual care strategy will receive omeprazole 40mg daily regardless of the results of their upper endoscopy and reflux testing.

Participants will meet with a study provider who will administer treatment according to assigned arm and provide recommended lifestyle modifications.

Participants will complete an online survey weekly to indicate if they have taken their oral capsule daily and if they have incorporated recommended lifestyle modifications.

Intervention visits will take place during week 1, week 4, and week 8. After the week 8 intervention visit is complete, participants will be told which strategy they were assigned to, if they are taking omeprazole 40mg or placebo, and be transitioned back to clinical care.

The most common risks or discomforts of this study are emotional upset during symptom reflection and side effects of omeprazole. The most serious risks include side effects of omeprazole which include generally mild side effects: headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence.

Inclusion criteria

• 18-89 years of age
• >8 weeks of laryngeal symptoms (cough, throat clearing, dysphonia)
• Standard evaluation for LPR, undergoing EGD (with endoscopic evaluation of the hypopharynx) and reflux monitoring off acid suppression
• Off acid suppression therapy for at least 2 weeks prior to randomization.

Exclusion criteria

• PPI intolerance and/or known hypersensitivity to the formulation or substituted benzimidazoles
• History of foregut surgery
• Known diagnosis of achalasia
• Inability to fast for 4 hours (no food or drink)
• Active tobacco use
• Pregnant or breastfeeding
• Unable to consent in English or Spanish
• Unable to provide consent without a legal guardian or representative
• Imprisoned
• Endoscopic findings conclusive with esophageal mucosal abnormalities
• Unable to proceed with reflux monitoring
• Use of acid suppression during the reflux monitoring and/or before the study medication (omeprazole or placebo) is dispensed
• Prior LRT for reflux related symptoms
• History of major psychiatric comorbidity
• Unable to attend in person study visits at UCSD