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The Effectiveness of Topical Silver Colloid in Treating Patients With Recalcitrant Chronic Rhinosinusitis (CRS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02403479
Recruitment Status : Completed
First Posted : March 31, 2015
Results First Posted : November 15, 2019
Last Update Posted : November 15, 2019
Sponsor:
Information provided by (Responsible Party):
Leigh Sowerby, Lawson Health Research Institute

Tracking Information
First Submitted Date  ICMJE March 1, 2015
First Posted Date  ICMJE March 31, 2015
Results First Submitted Date  ICMJE April 11, 2017
Results First Posted Date  ICMJE November 15, 2019
Last Update Posted Date November 15, 2019
Actual Study Start Date  ICMJE December 10, 2015
Actual Primary Completion Date March 6, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2019)
  • Change in Sino-nasal Outcome Test-22 Score Between Baseline and 6 Weeks, Then 6 Weeks to 12 Weeks. [ Time Frame: 6 weeks ]
    The Sinonasal Outcome Test-22 is a quality of life questionnaire examining the social and emotional distress of CRS. The scores range from 0 to 110 with higher scores representing more severe disease. Total score is reported. Higher values are a worse outcome.
  • Change in Endoscopic Lund-Kennedy Score From Baseline to 6 Weeks, Then 6 Weeks to 12 Weeks [ Time Frame: 6 weeks ]
    Endoscopic evaluation of the individual paranasal sinuses (left and right) and the degree of obstruction of the osteomeatal unit. Scores range from 0 to 24 with a higher number representing more severe disease.
Original Primary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
Number of participants with clinical improvement of sinonasal symptoms as a measure of post treatment changes in SNOT-22, Lund Kennedy and SIT test scores [ Time Frame: Three months ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
The reduction of overall cost of treatment of recalcitrant CRS as a comparable measure between the price of silver colloid and standard therapies [ Time Frame: Three months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effectiveness of Topical Silver Colloid in Treating Patients With Recalcitrant Chronic Rhinosinusitis
Official Title  ICMJE Phase 2 Study Examining the Effects of Topical Intranasal Silver Colloid in Patients With Recalcitrant Chronic Rhinosinusitis
Brief Summary Chronic rhinosinusitis without polyposis (CRSsP) is a very common condition that occurs when the lining of the sinuses becomes persistently irritated. Standard management options include topical steroids, antibiotics and surgery, but treatment-resistant CRSsP is frequently encountered. Bacterial biofilms are routinely detected within the nasal mucosa of CRSsP patients and are now thought to play an important role in the protracted nature of the disease. Colloidal silver is a widely used naturopathic agent that has recently been shown to eliminate bacteria, and in particular in vitro sinusitis biofilms, in laboratory studies. Although silver is currently used in a variety of chronic wound therapies, it has not yet been formally studied in people with CRSsP. It is our intention with this project to determine whether colloidal silver is a useful treatment strategy for patients with refractory CRS.
Detailed Description

The paranasal sinuses are within the bones of the face and head. Six paired sinuses are present in humans, and although their exact function is a topic for debate, they appear to play several roles ranging from cushioning the brain during trauma to increasing resonance of the voice and releasing nitric oxide to help with lung physiology. The sinuses are lined with a layer of respiratory epithelium that normally secretes a small amount of mucus to keep the sinuses lubricated and contains cilia to help sweep away debris. Rhinosinusitis occurs when this lining gets infected or irritated which can lead to excessive mucus production and impaired mucus drainage. It is a very prevalent condition affecting up to 16% of the population and is the fifth most common diagnosis generating an antibiotic prescription1,2.

Chronic rhinosinusitis without polyposis (CRSsP) is characterized by persistent symptoms of nasal congestion, mucus discharge from the nose, facial pain or anosmia for at least three months. Unlike acute rhinosinusitis, which is usually caused by infection, CRSsP can have more elusive causes and can be profoundly more complicated.3 Due to the challenging nature of CRS, physicians often use a variety of treatment strategies against it.3 Potential treatments for CRSsP include lifestyle modifications (quitting smoking, reduce allergen exposure, etc.), nasal saline irrigations, nasal corticosteroid spray or irrigations, antibiotics and surgery. Typically, there is a stepwise fashion to the therapy offered to patients whereby the more aggressive or invasive modalities are reserved for those who did not benefit from simpler approaches. Even despite all these regimens there is a small subset of patients who continue to fare poorly. One thought toward the reason for this centers on the frequent presence of biofilms within the sinuses of recalcitrant CRSsP patients.4

Biofilms have been reported in CRS populations for a decade now by a number of authors.4,5 Furthermore, their presence has been linked to more severe disease both pre and post-operatively. Using fluorescence in situ hybridization investigators have been able to identify staphylococcus aureus (S. aureus) and Haemophilus influenza (H. influenza) as the most common biofilm-forming organisms.5 In fact, H. influenza biofilms seem to be more common in milder patterns of CRS, whereas S. aureus biofilms are present in more severe, refractory forms of the disease.5 A very recently published study demonstrated colloidal silver directly attenuating S. aureus biofilms in vitro and herein lays the premise of our study.6

Interest in colloidal silver, a commercially available naturopathic product, was sparked after clinical improvements were seen in a number of recalcitrant CRS patients who sprayed the agent intranasally. Silver has long been used for its bactericidal properties, as it is one of the most toxic elements to microorganisms.7 Silver-impregnated dressings and catheters are currently used in the treatment of burns, ulcers and chronic wounds. Clear advantages of silver over modern antibiotics include broad spectrum activity against Gram-positive and Gram-negative organisms, fungi, protozoa and some viruses as well as the general absence of resistance developing in a number of bacterial species.7,8 In addition, silver has been shown to have activity against Pseudomonas aeruginosa biofilm development.9

The main reasons colloidal silver fell out of use as an antiseptic are due in large part to the advent of antibiotics, uncertain safety, and the production of argyria on ingestion10. Although it is not yet known which dose of silver is required to cause argyria, all case reports to date are following excessive daily consumption of the element over a period of years10,11. Topical application of silver has been reported to cause localized argyria whereas systemic toxicity is generally the result of longstanding oral intake12. Argyria is more or less a benign condition characterized by a slate-grey metallic appearance of the skin. Apart from skin discoloration, extreme cases of systemic silver toxicity can be associated with thrombocytopenia, abnormal clotting, renal impairment, proteinuria, and neurological symptoms such as seizures, loss of coordination and sensory loss12. All of these possible side effects are exceedingly rare and are not expected to be an issue in this study. There is, however, a possibility that there might be localized pigmentation of the nasal mucosa, of which there are no significant consequences13.

Our goal with this project is to test whether topical silver colloid is a feasible treatment option for patients with refractory CRS. With the recent publication of a proof of mechanism study6, the investigators are looking to extend the same notion into a proof of concept investigation. The investigators propose taking twenty volunteer patients with recalcitrant CRS and trial randomized to a course of daily intranasal silver colloid for 6 weeks followed by saline, or vice versa. Pre and post-treatment measurements will be taken using validated scoring systems for CRS patients14-16. These include the Sino-Nasal Outcome Test (SNOT-22)14, Lund-Kennedy score15 and the Smell Identification Test16, which examine quality of life indices, endoscopic assessments and sense of smell, respectively. Should the results of this preliminary study be in favor of silver colloid use in CRS patients the investigator should look into arranging a formal Randomized-Controlled Clinical Trial.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Rhinosinusitis
Intervention  ICMJE
  • Drug: Silver Colloid
    Topical silver colloid will be administered for 6 weeks. This will either occur before topical saline nasal spray. Participants are randomized as to the order of sprays. The commercially available silver colloid product, Sovereign Silver Mineral Supplement, will be used.
    Other Name: Silver Hydrosyl by Sovereign Silver
  • Other: Saline
    Topical saline will be administered for 6 weeks. This will occur before the topical silver colloidal nasal spray. Participants are randomized as to the order of sprays.
Study Arms  ICMJE
  • Experimental: Saline then Silver Colloid
    Each participant uses 6 weeks of Saline first (Frequency= 2 sprays twice daily; Route= topical intra-nasal spray; Duration= 6 weeks) followed by 6 weeks of silver colloid (Dose= 6.7mcg silver daily; Frequency= 2 sprays twice daily; Route= Topical intra-nasal spray; Duration= 6 weeks)
    Interventions:
    • Drug: Silver Colloid
    • Other: Saline
  • Experimental: Silver Colloid then Saline
    Each participant uses 6 weeks of Silver Colloid first (Dose= 6.7mcg silver daily; Frequency= 2 sprays twice daily; Route= Topical intra-nasal spray; Duration= 6 weeks) followed by 6 weeks of saline (Frequency= 2 sprays twice daily; Route= topical intra-nasal spray; Duration= 6 weeks).
    Interventions:
    • Drug: Silver Colloid
    • Other: Saline
Publications * Scott JR, Krishnan R, Rotenberg BW, Sowerby LJ. The effectiveness of topical colloidal silver in recalcitrant chronic rhinosinusitis: a randomized crossover control trial. J Otolaryngol Head Neck Surg. 2017 Nov 25;46(1):64. doi: 10.1186/s40463-017-0241-z.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 25, 2019)
22
Original Estimated Enrollment  ICMJE
 (submitted: March 30, 2015)
20
Actual Study Completion Date  ICMJE April 8, 2017
Actual Primary Completion Date March 6, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • A history of twelve or more weeks with at least 2 of the following:

    • Nasal congestion
    • Mucus discharge from the nose or mucus that drips down the back of the throat
    • Facial pain or pressure
    • A decrease sense of smell
  • A history of at least 2 of the following

    • One or more failed functional endoscopic sinus surgeries for CRS
    • Failed oral, culture-directed antibiotic therapy for CRS
    • Failed oral or topical steroid therapy for CRS
    • Failed baby shampoo nasal irrigation therapy for CRS
    • Failed topical mupirocin therapy for CRS
    • Failed Manuka honey irrigations for CRS
    • Failed budesonide irrigations for CRS

Exclusion Criteria:

  • Patients with nasal polyposis
  • Patients with existing autoimmune disorders
  • Patients with an allergy to silver
  • Patients with diabetes
  • Patients that have previously used colloidal silver as a naturopathic remedy
  • Patients that are pregnant, attempting/planning to become pregnant or breastfeeding
  • Patients below the age of 18 years
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02403479
Other Study ID Numbers  ICMJE 106309
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Leigh Sowerby, Lawson Health Research Institute
Study Sponsor  ICMJE Lawson Health Research Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Leigh Sowerby, MD Schulich School of Medicine and Dentistry/Otolaryngology
PRS Account Lawson Health Research Institute
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP