Laryngopharyngeal Reflux (LPR) is a common condition that causes symptoms like chronic cough, throat clearing, hoarseness, and trouble swallowing. If not treated, LPR can lead to long-term throat damage and may increase the risk of throat cancer. More than 20% of the people in the United States are estimated to have LPR, yet there is no effective medication approved to treat it. Drugs called proton pump inhibitors (PPIs) are often used to treat LPR, even though they were designed for stomach acid problems. These medications reduce acid but do not stop reflux from happening, so they often do not help LPR patients. Despite poor results, PPIs are widely prescribed, are very costly, and can cause side effects. Research shows that a digestive enzyme called pepsin plays a key role in LPR. Pepsin can damage the throat and voice box even when acid is not present. Laboratory studies found that certain HIV medications can block damage caused by pepsin. People taking these medications for HIV appear to have a much lower rate of LPR. This study will test fosamprenavir, an FDA-approved HIV drug, as a treatment for LPR. We will conduct a 14-week, double-blind, placebo-controlled clinical trial in patients with LPR who did not improve with standard treatment. Participants will receive either fosamprenavir or placebo, randomly, and symptoms will be measured before and after treatment using standard questionnaires and daily symptom tracking. Because there is no effective medical treatment for LPR. this study aims to test a safe, existing drug that targets the underlying cause of the disease.
Laryngopharyngeal reflux (LPR) causes chronic cough, throat clearing, hoarseness, and dysphagia and if left untreated can promote the development of laryngeal cancer. More than 20% of the United Stated population suffer from LPR, yet there is no effective medical therapy. Proton pump inhibitors (PPIs), which inhibit gastric acid production but do not prevent reflux events, continue to be prescribed for LPR despite their poor efficacy for this patient population, high cost ($26 billion/year), and associated risks. Pepsin, detected in the airway of these patients and now known to cause laryngeal inflammation and promote disease independent of gastric acid, is a key therapeutic target. We report preclinical studies of select HIV inhibitors that bind to and inhibit pepsin and thus hold promise for the treatment of LPR. In support, a very low incidence of LPR was found in patients taking these drugs compared to the general population. HIV inhibitors are ideal drugs to repurpose because they target a foreign virus. Thus, a repurposing approach can be used to safely perform proof of concept testing of the efficacy of a pepsin inhibitor for LPR. The objective of this study is to evaluate the efficacy and safety of fosamprenavir (FOS), administered orally for improving symptoms of laryngopharyngeal reflux (LPR). The Specific Aim of this project is to perform a 12-week randomized, double-blind, placebo-controlled clinical trial to assess the efficacy of fosamprenavir pills for LPR. Fosamprenavir will be used at the FDA approved, manufacturers recommended dose for HIV for 12 weeks in medically refractory patients with clinically diagnosed moderate/severe LPR and combined multi-channel intraluminal impedance - pH (MII-pH) confirmed laryngeal reflux events. Routine clinical outcome measures for LPR (Reflux Symptom Index, Reflux Finding Score, Voice Handicap Index) will be documented pre- and post-treatment with Oral Fosamprenavir for LPR (n = 52) and placebo (n = 52). Additional research measures will include repeat administration of a newly created Daily Symptom Reflex Diary, as well as an intermittently distributed Patient Global Impression - Static \& Change scales. Participants for this study will be recruited from the Department of Otolaryngology (ENT) at Froedtert Hospital in Milwaukee, Wisconsin. Patients seen by Froedtert ENT laryngologists who receive a diagnosis of laryngopharyngeal reflux (LPR) during a standard-of-care visit will be informed about the study and offered additional information regarding participation. Individuals interested in participating will be invited to attend a separate screening and consent visit at the Adult Translational Research Unit (ATRU) on campus. The study consists of eight research visits, including the screening/consent visit, conducted over approximately 14 weeks. Up to two study visits may be completed remotely (Visit 2 and Visit 8). Data will be collected from participant medical charts for the 3 standard-of-care clinic visits; Clinic visit 1 \& 2 are for diagnosis of LPR, while clinic visit 3 is a follow-up that occurs 14 weeks after visit 1 \& 2.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
104
A repurposing approach, prospective, placebo-controlled clinical trial of Fosamprenavir (used at 1,400 mg fosamprenavir calcium, twice daily) for 12 weeks in medically refractory patients with clinically diagnosed moderate/severe LPR (RSI \> 13, RFS \> 7 and MII-pH confirmed laryngeal reflux event\[s\]).
Non-active placebo pill formulation
Froedtert Hospital
Milwaukee, Wisconsin, United States
RECRUITINGChange in Reflux Symptom Index (RSI)
The absolute change from baseline (i.e., Pretreatment) in symptom severity as indicated by RSI Score over time, with the primary treatment comparison at Week 12 (End of Treatment Visit)
Time frame: Baseline to 12-week post-treatment.
Change in Daily Symptom Reflux Diary (DRSD)
The absolute change from baseline (i.e., Pretreatment) in symptom severity as indicated by Weekly Total DRSD Score (WTDS) over time, with the primary treatment comparison at Week 12 (End of Treatment Visit)
Time frame: Baseline to 12-week post-treatment.
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