Topical Irrigation Therapy for CRS

NCT02630472 | Terminated Phase 1 Results

• 1 other identifier: 821731
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the physiologic response of quinine-saline irrigations for acute exacerbation of uncomplicated chronic rhinosinusitis following endoscopic sinus surgery. Subjects who have previously had functional endoscopic sinus surgery with acute exacerbation of chronic rhinosinusitis will be randomized to either a quinine-saline or saline-placebo arm. The investigators will measure baseline and follow-up clinical and quality-of-life outcomes for both arms, and then compare the groups at the end of the study period. The investigators' hypothesis is that the participants in the quinine sulfate arm will perform better on all measures as compared to the control arm.

Conditions

Rhinitis; Sinusitis

Outcome Measures

Primary Outcomes (1)

• Change in Microbiome Profile

  Pre and post treatment endoscopically-obtained sinonasal microbiologic cultures.

  Baseline, Week 2, and Week 10

Secondary Outcomes (3)

• Change in Lund-Kennedy Endoscope Score

  Baseline, Week 2, and Week 10

• Change in the 22-item Sinonasal Outcomes Test Score

  Baseline, Week 2, and Week 10

• Change in Sniffin' Stick-12 Score

  Baseline, Week 2 and Week 10

Other Outcomes (1)

• Rescue Antibiotics

  Week 2 and Week 10

Study Arms (2)

Quinine Sulfate

EXPERIMENTAL

Each study participant randomized into the experimental arm will receive 28 tubes with 1mg/ml (6 mls total) of quinine sulfate, as well as 28 3cc syringes with the mucosal atomizing devices. The solutions will be supplied in light-protected tubes. Patients will apply 3 mls of quinine sulfate to each nostril twice per day. Thus the patients will be exposed to a maximum of 12mls or 12.0 mg of quinine per day. The Investigational Drug Service (IDS) will prepare and record the distribution of the irrigant. The Clinical Research Coordinator or Clinical Research Nurse will pick up the solutions and will demonstrate the application to the subject. The application of the solution is exactly the same as if the study subject were to irrigate with regular saline as part of their daily regimen for chronic rhinosinusitis.

Drug: Quinine Sulfate

Placebo

PLACEBO COMPARATOR

The placebo arm will be spiked with Sucrose Octaacetate which has a bitter taste, but does not stimulate sinonasal nitric oxide production. Each study participant will receive 28 tubes with 0.5mg/ml sucrose octaacetate, as well as 28 3cc syringes with the mucosal atomizing devices. The solutions will be supplied in light-protected tubes. The placebo arm will mirror the experimental arm exactly, except for the treatment solution contained in the vials.

Drug: Placebo

Interventions

Quinine Sulfate DRUG

Our plan is to first study quinine against saline to determine efficacy and safety. The vast majority of patients with rhinosinusitis utilize low pressure / high volume (240mls) sinonasal lavage to cleanse the sinonasal cavity. The patients will be exposed to a maximum of 12mls or 12.0 mg of quinine. In standard tonic water, quinine is 8.3mg/100mls and thus an 8oz glass of Canada Dry tonic water has 19.6mg of quinine. Thus, the maximum systemic exposure in our study (assuming ingestion of the total nasal administration) is less than drinking one glass of tonic water / day. To put this in context, the therapeutic range of quinine to treat malaria is 10mg/kg true ileal digestibility (TID) (2100mg for a 70kg individual) nearly 200 X the dose the investigators are proposing.

Quinine Sulfate

Placebo DRUG

In order to blind the participants to which arm they have been randomized into, the placebo arm will contain saline solution spiked with 0.5 mg/ml sucrose octaacetate. This solution will produce a bitter flavor similar to the one produced by quinine. There is no evidence that sucrose octaacetate produces nitric oxide production in the sinonasal cavity, nor is there evidence that it has any side effects (it is used to wean babies off of pacifiers) so the investigators feel it is an effective and safe option for a placebo.

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients who have undergone Functional Endoscopic Sinus Surgery (FESS)
• Purulent drainage on nasal endoscopy
• Male or female subjects, 18 years of age or older
• Patients seen at the Dept. of Otorhinolaryngology clinic at Hospital of the University of Pennsylvania (HUP), a tertiary care clinic

You may not qualify if:

• Pregnant women
• Immunocompromised patients
• Granulomatous diseases with rhinologic manifestations (Wegner's, Sarcoid, Churg-Strauss)
• Primary ciliary dyskinesia

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Rhinitis; Sinusitis

Interventions

Quinine

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases

Intervention Hierarchy (Ancestors)

Cinchona Alkaloids; Alkaloids; Heterocyclic Compounds; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Nithin D. Adappa, Principal Investigator
• Organization: UPenn

Nithin.Adappa@uphs.upenn.edu

215-662-2360

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: December 15, 2015
• Study Start: October 1, 2015
• Primary Completion: May 4, 2017
• Study Completion: May 4, 2017
• Last Updated: March 13, 2019
• Results First Posted: March 13, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)