Clinical Trial: Trial of Topical Verapamil in Chronic Rhinosinusitis With Nasal Polyps

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase Ib/II Clinical Trial of Topical Verapamil Hydrochloride for Chronic Rhinosinusitis With Nasal Polyps

Brief Summary: Verapamil is an L-type calcium channel blocker(CCB) which has been shown to reduce inflammation in a variety of tissues. Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by eosinophilic inflammation as well as P-gp overexpression. A previous trial of oral Verapamil showed preliminary efficacy for the treatment of CRSwNP. The goal of this study is to evaluate the safety and efficacy of intranasal Verapamil in CRSwNP.

Detailed Summary:

CRSwNP is a prevalent disease associated with major direct and indirect costs. Acute and Chronic Rhinosinusitis are estimated to affect up to 16% of the US population. They account for approximately 11 million or 1% of all office visits per year in the US and are the most common cause for antibiotic prescriptions in the community. CRS alone impacts more than 30 million Americans resulting in $6.9 to $9.9 billion in annual healthcare expenditures and $12.8 billion in productivity costs. The subset of patients in Europe with CRSwNP has been estimated to be between 2 and 4.3% and is thought to be similar in the US. This population remains one of the most challenging subgroups of CRS to manage effectively.

Recent evidence has focused on the sinonasal epithelial cell as a primary driver of the local dysregulated immune response through secretion of type 2 helper T-cell(Th2) promoting cytokines. While these studies suggest that epithelial cells are capable of orchestrating a local immune response, the mechanisms responsible for regulating cytokine secretion are poorly understood and may be influenced by the efflux function of epithelial P-glycoprotein(P-gp). Studies by the investigator's group have demonstrated that P-gp is overexpressed in the mucosa of patients with Th2 skewed CRS endotypes including CRSwNP and is capable of regulating the secretion of Th2 polarizing cytokines. Together, these findings suggest that P-gp participates in the non-canonical regulation of cytokine secretion within CRSwNP and may thereby represent a druggable target.

The investigator's group therefore undertook a randomized, double-blind, placebo-controlled trial to test the efficacy of low dose oral Verapamil HCl, a known first generation P-gp inhibitor, for the treatment of CRSwNP. Our findings demonstrated significant efficacy in both of the prim
Sponsor: Benjamin Bleier

Current Primary Outcome:

• Dose Limiting Toxicity [ Time Frame: 1-8 weeks ]
  Dose Limiting Toxicity will be defined as a development of 2nd or 3rd degree heart block as measured by an EKG. (Phase Ib primary outcome)
• Sinonasal Outcomes Test (SNOT-22) [ Time Frame: 1-4 weeks ]
  The Sinonasal Outcomes Test is a validated 22 point symptom scale. It will be the primary outcome measure for Phase II.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Intermediate toxicity as defined by cardiac effects [ Time Frame: 1-8 weeks ]
  Intermediate toxicity will be defined as: a heart rate of <50, an asymptomatic BP reduction >30% from baseline or SBP <90mmHg, an asymptomatic AMP reduction >30% from baseline or MAP<55, an asymptomatic DBP reduction >30% from baseline, and a Meltzer Compliance Grade >4 (Phase Ib Secondary Outcome I)
• Mild toxicity as defined by Meltzer compliance grade [ Time Frame: 1-8 weeks ]
  Mild toxicity will be defined as a Meltzer Compliance Grade of 2-3. (Phase Ib Secondary Outcome II)
• Lund-Kennedy Score (LKS) [ Time Frame: 1-4 weeks ]
  Lund-Kennedy Score is an objective measure of the pathologic state of the sinuses. (Phase II Secondary Outcome)
• Subjective 10cm Visual Analog Scale [ Time Frame: 1-4 weeks ]
  The 10cm VAS is a subjective measure of overall symptom severity. (Phase II Secondary Outcome)
• Meltzer Satisfaction and Compliance Scores [ Time Frame: 1-4 weeks ]
  The Meltzer Satisfaction and Compliance Scores are a subjective measure of satisfaction with the nasal irrigation. (Phase II Secondary Outcome)

Original Secondary Outcome: Same as current

Information By: Massachusetts Eye and Ear Infirmary

Dates:
Date Received: February 14, 2017
Date Started: June 2017
Date Completion: July 2019
Last Updated: May 2, 2017
Last Verified: May 2017