Use of Probiotics as Adjunctive Treatment for Chronic Rhinosinusitis

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT00396162
• Collaborator: Institut Rosell (Other)
• Enrollment: 77
• Arms: 2
• Duration (Months): 15

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Rhinosinusitis	Drug: probiotic containing L.rhamnosus R0011 strain; Other: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Use of Probiotics as Adjunctive Treatment for Chronic Rhinosinusitis
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo pill Placebo pills on same schedule as active intervention.	Other: Placebo; Placebo pill
Active Comparator: Probiotic L. rhamnosus R0011 strain	Drug: probiotic containing L.rhamnosus R0011 strain; 500 million active cells of L rhamnosus R0011 strain per tablet bid for 4 weeks; Other Names: L rhamnosus R0011

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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)

3. Mean Number of Days of Steroid Spray Use for Each Group [8 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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):

1. More than 12 consecutive weeks of symptomatic nasal obstruction and, B. More than 12 weeks of symptomatic nasal discharge.

1. An Otolaryngologist evaluation and diagnosis of chronic inflammatory rhinosinusitis (hyperplastic mucosa, polyps in absence of overt bacterial infection)

2. 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Michigan
• Institut Rosell

Investigators

• Principal Investigator: Jeffrey E Terrell, MD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeffrey E. Terrell, M.D., Professor of Otolaryngology, University of Michigan
• ClinicalTrials.gov Identifier: NCT00396162
• Other Study ID Numbers: HUM00006212
• First Posted: Nov 6, 2006
• Last Update Posted: Sep 20, 2016
• Last Verified: Aug 1, 2016

• Additional relevant MeSH terms: Sinusitis

Study Results

Participant Flow

Recruitment Details	82 participants were screened . 77 enrolled.

Arm/Group Title	Probiotic	Placebo
Arm/Group Description	The study protocol scheduled daily oral supplementation of either the probiotic or the placebo twice daily for four weeks. The probiotic product was a chewable tablet containing 500 million active cells of L rhamnosus R0011 strain per tablet. Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.	Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.
Period Title: Overall Study
STARTED	39	38
COMPLETED	37	35
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Probiotic	Placebo Pill	Total
Arm/Group Description	drug probiotic containing L.rhamnosus R0011 strain: 500 million active cells of L rhamnosus R0011 strain per tablet bid for 4 weeks	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	Total of all reporting groups
Overall Participants	39	38	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.4 (12.6)	49.6 (8.6)	49.5 (10)
Sex: Female, Male (Count of Participants)
Female	19 48.7%	25 65.8%	44 57.1%
Male	20 51.3%	13 34.2%	33 42.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.1%	3 7.9%	5 6.5%
Not Hispanic or Latino	37 94.9%	35 92.1%	72 93.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
asthma (participants) [Number]
No asthma	14 35.9%	14 36.8%	28 36.4%
intermittent and mild asthma	13 33.3%	10 26.3%	23 29.9%
moderate-severe asthma	12 30.8%	14 36.8%	26 33.8%
aspirin sensitivity (participants) [Number]
Aspirin Sensitivity	12 30.8%	12 31.6%	24 31.2%
No aspirin sensitivity	27 69.2%	26 68.4%	53 68.8%
SinoNasal Outcome Test Score (SNOT-20) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	36.4 (16.2)	39.5 (19.8)	37.9 (17.9)

Outcome Measures

1. Primary Outcome

Title	Mean Reduction in SNOT-20 Scores
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Probiotic	Placebo
Arm/Group Description	The study protocol scheduled daily oral supplementation of either the probiotic or the placebo twice daily for four weeks. The probiotic product was a chewable tablet containing 500 million active cells of L rhamnosus R0011 strain per tablet. Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.	Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.
Measure Participants	37	35
Mean (Standard Deviation) [units on a scale]	1.8 (12)	5.5 (14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotic, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Side Effect Summary
Description	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

Outcome Measure Data

Analysis Population Description

The sample size on the placebo side is reduced due to some study participants not reporting their 8 week survey

Arm/Group Title	Placebo Pill	Probiotic
Arm/Group Description	Placebo pills on same schedule as active intervention. Placebo: Placebo pill	L. rhamnosus R0011 strain probiotic containing L.rhamnosus R0011 strain: 500 million active cells of L rhamnosus R0011 strain per tablet bid for 4 weeks
Measure Participants	35	37
Number [participants]	17 43.6%	14 36.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotic, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.31
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Mean Number of Days of Antibiotic Use During the Study Period (0-8 Weeks)
Description	Mean number of days that antibiotics were used in the subgroup (placebo vs Probiotic arm)
Time Frame	At 8 weeks after baseline measures

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active Intervention
Arm/Group Description	Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.	The study protocol scheduled daily oral supplementation of either the probiotic or the placebo twice daily for four weeks. The probiotic product was a chewable tablet containing 500 million active cells of L rhamnosus R0011 strain per tablet. Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.
Measure Participants	35	37
Mean (Standard Deviation) [days]	1.9 (5.5)	0.8 (2.7)

4. Secondary Outcome

Title	Mean Number of Days of Steroid Spray Use for Each Group
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Probiotic	Placebo
Arm/Group Description	The study protocol scheduled daily oral supplementation of either the probiotic or the placebo twice daily for four weeks. The probiotic product was a chewable tablet containing 500 million active cells of L rhamnosus R0011 strain per tablet. Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.	Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.
Measure Participants	37	35
Mean (Standard Deviation) [days]	2.8 (7.4)	0.4 (2.2)

Adverse Events

Arm/Group Title	Active Intervention		Placebo
Arm/Group Description	The study protocol scheduled daily oral supplementation of either the probiotic or the placebo twice daily for four weeks. The probiotic product was a chewable tablet containing 500 million active cells of L rhamnosus R0011 strain per tablet. Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.		Placebo tablets comparable to the probiotic in color, weight, texture, and flavor were also available.
All Cause Mortality
	Active Intervention		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active Intervention		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Active Intervention		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/39 (35.9%)		17/38 (44.7%)
Gastrointestinal disorders
bloating	7/39 (17.9%)		9/38 (23.7%)
diarrhea	8/39 (20.5%)		10/38 (26.3%)
abdominal pain	7/39 (17.9%)		7/38 (18.4%)
loose stools	9/39 (23.1%)		8/38 (21.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.