The Mechanism Versus PPI Trial (MVP)

University of California San Diego

Status and phase: Enrolling; Phase 4

Conditions: Throat Clearing; Cough; Dysphonia; Laryngopharyngeal Reflux; Reflux

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06999577

807412

R01DK139089 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 160 estimated patients

Sex: All

Ages: 18 to 89 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 18-89 years of age
2. >8 weeks of laryngeal symptoms (cough, throat clearing, dysphonia)
3. Standard evaluation for LPR, undergoing EGD (with endoscopic evaluation of the hypopharynx) and reflux monitoring off acid suppression
4. Off acid suppression therapy for at least 2 weeks prior to randomization.

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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160 participants in 2 patient groups

Mechanism Guided Strategy

Active Comparator group

Description:

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.

Treatment:

Behavioral: Laryngeal Recalibration Therapy

Drug: Omeprazole 40 MG

Behavioral: GERD Lifestyle Recommendations

Usual Care Strategy

Active Comparator group

Description:

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.

Treatment:

Drug: Omeprazole 40 MG

Behavioral: GERD Lifestyle Recommendations