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RhinosinusitisPhase 1/2CRSNCT02403479

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

A Phase 1/2 study testing Silver Colloid and Saline in people with Rhinosinusitis, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rhinosinusitis
What is being tested?
Silver Colloid and Saline
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
2 sitesCanada
Study dates
10 Dec 2015to 8 Apr 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

Canada2 sites
  • Saint Joseph's Health Care

    London, Ontario, N6A 4V2

  • St. Joseph's Health Care

    London, Ontario

Other trials in Canada

About this study

Official title: Phase 2 Study Examining the Effects of Topical Intranasal Silver Colloid in Patients With Recalcitrant Chronic Rhinosinusitis

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.

Read the 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.

Conditions
Rhinosinusitis
Being tested
Silver Colloid, Saline
Medical subject headings
Rhinosinusitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Silver ColloidDrug

    Also called Silver Hydrosyl by Sovereign Silver

    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.

  • SalineOther

    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 groups in NCT02403479
Study groupRoleWhat they receive
Saline then Silver ColloidExperimentalEach 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)
Receives: Drug: Silver Colloid; Other: Saline
Silver Colloid then SalineExperimentalEach 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).
Receives: Drug: Silver Colloid; Other: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Sino-nasal Outcome Test-22 Score Between Baseline and 6 Weeks, Then 6 Weeks to 12 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.

    Measured: 6 weeks

  2. Change in Endoscopic Lund-Kennedy Score From Baseline to 6 Weeks, Then 6 Weeks to 12 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.

    Measured: 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2015 (estimated)
  2. Study start10 Dec 2015
  3. Primary completion6 Mar 2016
  4. Study completion8 Apr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02403479
Sponsor's protocol ID
106309
Acronym
CRS
Status last verified
Oct 2019
First submitted
1 Mar 2015
Last updated
15 Nov 2019
Data monitoring committee
No
Individual data sharing
No

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.

    PubMed 29178954

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Silver Colloid and Saline in people with Rhinosinusitis, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Sino-nasal Outcome Test-22 Score Between Baseline and 6 Weeks, Then 6 Weeks to 12 Weeks. (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02403479, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2019.

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