The Mechanism Versus PPI Trial

NCT06999577 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 807412R01DK139089
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if a mechanism guided strategy that utilizes a multidisciplinary approach to treat adults patients (age 18-89) with chronic throat symptoms who are undergoing clinical evaluation for laryngopharyngeal reflux (LPR) is more effective than the usual care strategy with proton pump inhibitor (PPI) therapy used in gastroenterology for these patients. The main question it aims to answer is: Will a greater proportion of the mechanism guided strategy participants achieve symptom response in comparison to the usual care strategy participants? If there is a comparison group: Researchers will compare the mechanism guided strategy to usual care strategy to see if treatment response differs between the groups. Participants will be be asked to do the following:

• participate in an 8-week blinded study phase where they will be randomized to either 1) Mechanism Guided Strategy or 2) Usual Care Strategy
• take an oral capsule daily (omeprazole 40mg or placebo)
• come to 3 in-person visits at UC San Diego Health for an intervention visit with a study provider
• consider incorporating recommended lifestyle modifications
• complete weekly surveys

Conditions

Laryngopharyngeal Reflux; Cough; Throat Clearing; Dysphonia; Reflux

Outcome Measures

Primary Outcomes (1)

• Symptom Response

  Proportion of subjects with symptom response measured by the reflux symptom index (RSI) score.

  5 years

Secondary Outcomes (1)

• Diagnostic Methods for LPR

  5 years

Study Arms (2)

Mechanism Guided Strategy

ACTIVE COMPARATOR

1\) 8-week course of double dose PPI or placebo; 2) Laryngeal Recalibration Therapy (LRT) with speech language pathologist (SLP). Subjects will receive PPI if their reflux monitoring is consistent with GERD and placebo if it is not consistent with GERD. SLP will administer LRT: LRT utilizes therapies that SLPs standardly utilize (mechanical and cognitive guidance) in combination specifically designed to treat laryngeal symptoms. 1. Mechanical Guidance: The SLP will guide subjects through laryngeal suppression, changing voice production, and improving breath coordination. 2. Cognitive Guidance: The SLP will guide subjects through relaxation and conceptualization changes. 3. Lifestyle Recommendations: In addition to receiving LRT, subjects will be counseled on typical lifestyle recommendations for GERD, detailed in the Usual Care Strategy below.

Drug: Omeprazole 40 MG; Behavioral: Laryngeal Recalibration Therapy; Behavioral: GERD Lifestyle Recommendations

Usual Care Strategy

ACTIVE COMPARATOR

1\) an 8-week course of double dose PPI and 2) lifestyle counseling. This represents the control group receiving usual care and will serve as the study's active control group. In order to maintain group concealment, subjects will receive counseling from a study investigator on standard lifestyle modifications recommended for GERD at intervals mirroring that of the mechanism guided strategy: week 1, week 4, and week 8 which is also reflective of standard recommended follow-up and counseling in GERD management.

Drug: Omeprazole 40 MG; Behavioral: GERD Lifestyle Recommendations

Interventions

Omeprazole 40 MG DRUG

8 week double dose therapy of proton pump inhibitor or placebo.

Also known as: Prilosec, NDA 21-229

Mechanism Guided Strategy; Usual Care Strategy

Laryngeal Recalibration Therapy BEHAVIORAL

LRT utilizes therapies that SLPs standardly utilize (mechanical and cognitive guidance) in combination specifically designed to treat laryngeal symptoms. Each session with the SLP will guide subjects through these therapies. The existing script-based LRT protocol consists of the following: 1) mechanical guidance (laryngeal suppression, voice production, breath coordination), 2) cognitive guidance (identification of thinking patterns, recalibration of thoughts about laryngeal sensations).

Also known as: LRT

Mechanism Guided Strategy

GERD Lifestyle Recommendations BEHAVIORAL

This is the typical lifestyle recommendations for GERD used clinically.

Mechanism Guided Strategy; Usual Care Strategy

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of California San Diego

San Deigo, California, 92093, United States

RECRUITING

MeSH Terms

Conditions

Laryngopharyngeal Reflux; Cough; Dysphonia; Gastroesophageal Reflux

Interventions

Omeprazole

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Voice Disorders; Otorhinolaryngologic Diseases; Neurologic Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Rena Yadlapati, MD

  UC San Diego Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorijane Robles

CONTACT

858-246-5236; esophagealresearch@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The participant will not know which strategy group they are randomized to and they will not know which daily oral capsule (omeprazole 40mg or placebo) they have been dispensed. The study provider they meet with during intervention visits will not know the results of their upper endoscopy and reflux testing.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: 8 week intervention with a daily oral capsule (omeprazole 40mg or placebo) and 3 intervention visits at week 1, 4, and 8.

Study Record Dates

• First Submitted: May 22, 2025
• First Posted: May 31, 2025
• Study Start: June 4, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: The dataset will be available at the time of publication; all other generated scientific data will be shared no later than the end of the award. The study data will be stored in the repository for at least 5 years.
• Access Criteria: To maximize the appropriate sharing of scientific data and protect research participants' privacy and confidentiality, reuse of this dataset should use the following Data Use Limitations (DULs) under Controlled Access that is made available by a data repository only after approval of the request by the UCSD Health review panel process. * Health/Medical/Biomedical - The dataset can only be used for studying health, medical, or biomedical conditions and does not include the study of population origins or ancestry. * IRB Approval Required (IRB) - The requesting institution's IRB or equivalent body must approve the requested use.

Locations

US (1)