Chronic Rhinosinusitis
Conditions
Brief summary
Chronic sinusitis is reported to be one of the most widespread disorders in the United States. It can be caused by a variety of reasons such as allergy, infection and/or defects in T-cells which help regulate immune function. Medication and other costs related to treatment of nasal and sinus infections are estimated to be more than $60 million annually putting a considerable strain on the economy of health care. Probiotics are live microorganisms that are normally present in the gut of a healthy individual. They are also known as friendly bacteria and have been used to help maintain the normal functioning of the immune system. They are safe and are commercially available in the form of yoghurt, sachets, chewable tablets or flavored capsules. Since a number of nasal and sinus disorders are related to allergy and improper functioning of the immune system, we hypothesize that regular use of probiotics may help improve chronic nasal and sinus symptoms by boosting immune responses. The project we propose is novel because it would be the first study evaluating the usefulness of probiotics for the larger population having chronic sinusitis rather than those having only allergic symptoms. We aim to assess whether regular use of probiotics will help improve symptoms of chronic sinusitis and will have a greater effect than placebo in this regard.
Detailed description
Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. They are a part of the normal gastrointestinal flora and have safely been used to boost immune responses in patients with perennial and seasonal allergic rhinitis. Their exact mechanism of benefit is unknown but they primarily help to regulate T-cell function which is important in maintaining immune tolerance. Chronic rhinosinusitis is widely prevalent and affects nearly 16 million people in the US alone each year. It puts a strain on the health resources of the nation in terms of costs related to medications and surgery. Chronic rhinosinusitis can be caused by a variety of reasons including allergy/hypersensitivity, infection, nasal anatomical variations and T-cell regulatory dysfunction. We hypothesize that regular use of probiotics in patients with chronic rhinosinusitis will result in substantial improvement in their symptoms by boosting their immunity and may also help decrease their medication usage. Our study will be a double-blinded, randomized, control trial. We hope to recruit 100 patients from the University Otolaryngology and Allergy Clinics. Fifty patients will be randomized to the treatment (active) arm and 50 patients to the placebo arm. Subjects will be followed for 2 months during their period of participation in the study. The main aim of our study is to determine whether regular use of probiotics in patients with chronic rhinosinusitis helps improve their quality of life. Our main outcome of interest is a change in the mean score of the Sino-Nasal Outcome Test (SNOT-20) form in the treatment group and a greater change in the mean score of the SNOT-20 in the treatment arm as compared to the placebo arm. If probiotics are found to be effective, they may be used as a cost-effective, adjunctive therapy for patients with chronic rhinosinusitis.
Interventions
500 million active cells of L rhamnosus R0011 strain per tablet bid for 4 weeks
OTHERPlacebo
Placebo pill
Sponsors
Institut Rosell
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥15 and ≤70 years. 2. The patient must be bothered by each of the two following symptoms(\>50% of days in the last 3 months): A. More than 12 consecutive weeks of symptomatic nasal obstruction and, B. More than 12 weeks of symptomatic nasal discharge. 3. An Otolaryngologist evaluation and diagnosis of chronic inflammatory rhinosinusitis (hyperplastic mucosa, polyps in absence of overt bacterial infection) 4. Access to telephone (home or person cell).
Exclusion criteria
1. Sinus surgery within the last 3 months 2. Acute illness within the last 2 weeks requiring antibiotics: including: otitis media, pharyngitis, bronchitis, or laryngitis. 3. Immunosuppression (due to medications including oral steroids, or due to autoimmune diseases, HIV infection, cystic fibrosis, immunodeficiency, malignancies, uncontrolled diabetes mellitus, chronic renal failure, etc.) 4. Patients with chronic or acute bacterial sinusitis.(Clinical diagnosis-to be decided by MD) 5. An allergic reaction to a probiotic dietary supplement in the past (such as symptoms of tightness in the chest, breathing difficulties, skin hives, rash or other clinical symptoms consistent with sensitivity or intolerance) 6. Inability to speak or read English. 7. Pregnancy and Lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Reduction in SNOT-20 Scores | 8 weeks | Mean reduction (and Standard deviation) in SNOT-20 scores, from baseline to 8 week measurements. SinoNasal Outcome Test measures symptom severity. It is a summary score, ranging from 0 to 100 with 100 indicating worse symptoms. Since 100 represents more severe symptoms, the changes represented here are reductions in SNOT-scores, even though they are not expressed as negative numbers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Side Effect Summary | 8 weeks | Totals of all side effects for placebo group and treatment group over the course of the eight week trial (including patients who dropped from the study after baseline measurement). Individual categories of side-effects are listed in Adverse events section. |
| Mean Number of Days of Antibiotic Use During the Study Period (0-8 Weeks) | At 8 weeks after baseline measures | Mean number of days that antibiotics were used in the subgroup (placebo vs Probiotic arm) |
| Mean Number of Days of Steroid Spray Use for Each Group | 8 weeks | — |
Participant flow
Recruitment details
82 participants were screened . 77 enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Probiotic drug
probiotic containing L.rhamnosus R0011 strain: 500 million active cells of L rhamnosus R0011 strain per tablet bid for 4 weeks | 39 |
| Placebo Pill Placebo pills on same schedule as active intervention.
probiotic containing L.rhamnosus R0011 strain: 500 million active cells of L rhamnosus R0011 strain per tablet bid for 4 weeks | 38 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Probiotic | Placebo Pill | Total |
|---|---|---|---|
| Age, Continuous | 49.4 years STANDARD_DEVIATION 12.6 | 49.6 years STANDARD_DEVIATION 8.6 | 49.5 years STANDARD_DEVIATION 10 |
| aspirin sensitivity Aspirin Sensitivity | 12 participants | 12 participants | 24 participants |
| aspirin sensitivity No aspirin sensitivity | 27 participants | 26 participants | 53 participants |
| asthma intermittent and mild asthma | 13 participants | 10 participants | 23 participants |
| asthma moderate-severe asthma | 12 participants | 14 participants | 26 participants |
| asthma No asthma | 14 participants | 14 participants | 28 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 35 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 25 Participants | 44 Participants |
| Sex: Female, Male Male | 20 Participants | 13 Participants | 33 Participants |
| SinoNasal Outcome Test Score (SNOT-20) | 36.4 units on a scale STANDARD_DEVIATION 16.2 | 39.5 units on a scale STANDARD_DEVIATION 19.8 | 37.9 units on a scale STANDARD_DEVIATION 17.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 39 | 17 / 38 |
| serious Total, serious adverse events | 0 / 39 | 0 / 38 |
Outcome results
Primary
Mean Reduction in SNOT-20 Scores
Mean reduction (and Standard deviation) in SNOT-20 scores, from baseline to 8 week measurements. SinoNasal Outcome Test measures symptom severity. It is a summary score, ranging from 0 to 100 with 100 indicating worse symptoms. Since 100 represents more severe symptoms, the changes represented here are reductions in SNOT-scores, even though they are not expressed as negative numbers.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Probiotic | Mean Reduction in SNOT-20 Scores | 1.8 units on a scale | Standard Deviation 12 |
| Placebo | Mean Reduction in SNOT-20 Scores | 5.5 units on a scale | Standard Deviation 14 |
p-value: 0.23t-test, 2 sided
Secondary
Mean Number of Days of Antibiotic Use During the Study Period (0-8 Weeks)
Mean number of days that antibiotics were used in the subgroup (placebo vs Probiotic arm)
Time frame: At 8 weeks after baseline measures
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Probiotic | Mean Number of Days of Antibiotic Use During the Study Period (0-8 Weeks) | 1.9 days | Standard Deviation 5.5 |
| Placebo | Mean Number of Days of Antibiotic Use During the Study Period (0-8 Weeks) | 0.8 days | Standard Deviation 2.7 |
Secondary
Mean Number of Days of Steroid Spray Use for Each Group
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Probiotic | Mean Number of Days of Steroid Spray Use for Each Group | 2.8 days | Standard Deviation 7.4 |
| Placebo | Mean Number of Days of Steroid Spray Use for Each Group | 0.4 days | Standard Deviation 2.2 |
Secondary
Side Effect Summary
Totals of all side effects for placebo group and treatment group over the course of the eight week trial (including patients who dropped from the study after baseline measurement). Individual categories of side-effects are listed in Adverse events section.
Time frame: 8 weeks
Population: The sample size on the placebo side is reduced due to some study participants not reporting their 8 week survey
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Probiotic | Side Effect Summary | 17 participants |
| Placebo | Side Effect Summary | 14 participants |
p-value: 0.31t-test, 2 sided