NCT02454608

Brief Summary

Verapamil is an L-type calcium channel blocker(CCB) which has been shown to reduce inflammation in a variety of tissues. Verapamil has also been shown to improve eosinophilic inflammation in an animal model of asthma and also functions as a P-glycoprotein(P-gp) inhibitor. A major subtype of chronic rhinosinusitis(CRS) is characterized by eosinophilic inflammation as well as P-gp overexpression. The goal of this study is to therefore see whether Verapamil may be used to treat CRS.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
29

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started May 2015

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2015

Completed
10 days until next milestone

First Submitted

Initial submission to the registry

May 11, 2015

Completed
16 days until next milestone

First Posted

Study publicly available on registry

May 27, 2015

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2016

Completed
10 months until next milestone

Results Posted

Study results publicly available

December 28, 2016

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2017

Completed
Last Updated

June 14, 2018

Status Verified

May 1, 2018

Enrollment Period

10 months

First QC Date

May 11, 2015

Results QC Date

August 29, 2016

Last Update Submit

May 16, 2018

Conditions

SinusitisNasal Polyps

Outcome Measures

Primary Outcomes (4)

  • Subjective Sinonasal Symptoms on Sinonasal Outcomes Test-22(SNOT-22)

    Minimum Score: 0 Maximum Score: 110 A higher score indicates a worse outcome

    baseline to week 8

  • Subjective Sinonasal Symptoms on 10cm Visual Analogue Scale(VAS)

    Minimum Score: 0 Maximum Score: 100 A higher score indicates a worse outcome.

    baseline to week 8

  • Subjective Sinonasal Symptoms on Sinonasal Outcomes Test-22(SNOT-22)

    Minimum Score: 0 Maximum Score: 110 A higher score indicates a worse outcome

    baseline to week 56

  • Subjective Sinonasal Symptoms on 10cm Visual Analogue Scale(VAS)

    Minimum Score: 0 Maximum Score: 100 A higher score indicates a worse outcome.

    baseline to week 56

Secondary Outcomes (2)

  • Objective Sinonasal Symptoms on Lund-Kennedy Score(LKS)

    baseline to week 8

  • Objective Sinonasal Symptoms on Lund-McKay Score(LMS)

    Week 8

Other Outcomes (3)

  • Heart Rate

    Mean change between baseline and week 8 measurements.

  • Systolic Blood Pressure

    Mean change between baseline and week 8 measurements

  • Diastolic Blood Pressure

    Mean change between baseline and week 8 measurements

Study Arms (3)

Treatment

EXPERIMENTAL

Verapamil HCl, capsules for oral administration, 80mg, TID, for 8 weeks

Drug: Verapamil HCl

Control

PLACEBO COMPARATOR

Placebo, capsules for oral administration, TID, for 8 weeks

Other: Placebo

Open Label

EXPERIMENTAL

Verapamil HCl, capsules for oral administration, 80mg, TID, for 1 year

Drug: Verapamil HCl

Interventions

Verapamil HClDRUG

Verapamil represents a calcium channel blocker which binds to the alpha subunit of L-type voltage dependent calcium (Cav1) channels thereby blocking the influx of calcium ions into the host cell. While Verapamil is classically used to promote the relaxation of cardiac and smooth muscle cells, recent evidence has suggested that it may also function as an immunomodulator in astrocytes, hepatocytes, and T-cells. Further research has demonstrated that Verapamil is capable of specifically reducing Th2 associated inflammation in asthma. These findings raise the provocative question as to whether Verapamil could also be effective in reducing inflammation in chronic rhinosinusitis with nasal polyps.

Also known as: Verapamil
Open LabelTreatment
PlaceboOTHER

Capsule with the same characteristics (size, color, smell) as Verapamil HCl.

Control

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients presenting to the Massachusetts Eye and Ear Sinus Center
  • Age 18-80 yrs old
  • Diagnosed with Chronic Rhinosinusitis with Nasal Polyps according to the EPOS 2012 consensus criteria

You may not qualify if:

  • Patients with the following comorbidities:
  • GI Hypomotility
  • Heart Failure
  • Liver Failure
  • Kidney Disease
  • Muscular Dystrophy
  • Pregnant or Nursing Females
  • Steroid Dependency
  • Patients taking the following medications:
  • Aspirin
  • Beta-blockers
  • Cimetidine(Tagamet)
  • Clarithromycin(Biaxin)
  • Cyclosporin
  • Digoxin
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Related Publications (12)

  • Chin D, Harvey RJ. Nasal polyposis: an inflammatory condition requiring effective anti-inflammatory treatment. Curr Opin Otolaryngol Head Neck Surg. 2013 Feb;21(1):23-30. doi: 10.1097/MOO.0b013e32835bc3f9.

    PMID: 23172039BACKGROUND

  • Poetker DM, Jakubowski LA, Lal D, Hwang PH, Wright ED, Smith TL. Oral corticosteroids in the management of adult chronic rhinosinusitis with and without nasal polyps: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013 Feb;3(2):104-20. doi: 10.1002/alr.21072. Epub 2012 Aug 7.

    PMID: 22887970BACKGROUND

  • Khakzad MR, Mirsadraee M, Mohammadpour A, Ghafarzadegan K, Hadi R, Saghari M, Meshkat M. Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals. Pulm Pharmacol Ther. 2012 Apr;25(2):163-8. doi: 10.1016/j.pupt.2011.11.001. Epub 2011 Nov 25.

    PMID: 22133887BACKGROUND

  • Matsumori A, Nishio R, Nose Y. Calcium channel blockers differentially modulate cytokine production by peripheral blood mononuclear cells. Circ J. 2010 Mar;74(3):567-71. doi: 10.1253/circj.cj-09-0467. Epub 2010 Jan 30.

    PMID: 20118567BACKGROUND

  • Hashioka S, Klegeris A, McGeer PL. Inhibition of human astrocyte and microglia neurotoxicity by calcium channel blockers. Neuropharmacology. 2012 Sep;63(4):685-91. doi: 10.1016/j.neuropharm.2012.05.033. Epub 2012 May 30.

    PMID: 22659089BACKGROUND

  • Li G, Qi XP, Wu XY, Liu FK, Xu Z, Chen C, Yang XD, Sun Z, Li JS. Verapamil modulates LPS-induced cytokine production via inhibition of NF-kappa B activation in the liver. Inflamm Res. 2006 Mar;55(3):108-13. doi: 10.1007/s00011-005-0060-y.

    PMID: 16673153BACKGROUND

  • Bacon KB, Westwick J, Camp RD. Potent and specific inhibition of IL-8-, IL-1 alpha- and IL-1 beta-induced in vitro human lymphocyte migration by calcium channel antagonists. Biochem Biophys Res Commun. 1989 Nov 30;165(1):349-54. doi: 10.1016/0006-291x(89)91076-0.

    PMID: 2686646BACKGROUND

  • Becker WJ. Cluster headache: conventional pharmacological management. Headache. 2013 Jul-Aug;53(7):1191-6. doi: 10.1111/head.12145. Epub 2013 Jun 14.

    PMID: 23773141BACKGROUND

  • Cohen AS, Matharu MS, Goadsby PJ. Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology. 2007 Aug 14;69(7):668-75. doi: 10.1212/01.wnl.0000267319.18123.d3.

    PMID: 17698788BACKGROUND

  • Lanteri-Minet M, Silhol F, Piano V, Donnet A. Cardiac safety in cluster headache patients using the very high dose of verapamil (>/=720 mg/day). J Headache Pain. 2011 Apr;12(2):173-6. doi: 10.1007/s10194-010-0289-x. Epub 2011 Jan 22.

    PMID: 21258839BACKGROUND

  • Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl. 2012 Mar;23:3 p preceding table of contents, 1-298.

    PMID: 22764607BACKGROUND

  • Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009 Oct;34(5):447-54. doi: 10.1111/j.1749-4486.2009.01995.x.

    PMID: 19793277BACKGROUND

MeSH Terms

Conditions

SinusitisNasal Polyps

Interventions

Verapamil

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsParanasal Sinus DiseasesNose DiseasesRespiratory Tract DiseasesOtorhinolaryngologic DiseasesPolypsPathological Conditions, AnatomicalPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PhenethylaminesEthylaminesAminesOrganic Chemicals

Results Point of Contact

Title
Benjamin Bleier
Organization
Massachusetts Eye and Ear Infirmary
Benjamin_Bleier@MEEI.HARVARD.EDU
(617) 573-6966

Study Officials

  • Benjamin S Bleier, MD

    Massachusetts Eye and Ear Infirmary

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

May 11, 2015

First Posted

May 27, 2015

Study Start

May 1, 2015

Primary Completion

March 1, 2016

Study Completion

May 1, 2017

Last Updated

June 14, 2018

Results First Posted

December 28, 2016

Record last verified: 2018-05

Data Sharing

IPD Sharing
Will not share

Locations

US(1)