Use of Probiotics as Adjunctive Treatment for Chronic Rhinosinusitis

• ClinicalTrials.gov Identifier: NCT00396162
• Recruitment Status: Completed
• First Posted: November 6, 2006
• Results First Posted: August 4, 2016
• Last Update Posted: September 20, 2016
• Sponsor: University of Michigan
• Collaborator: Institut Rosell
• Information provided by (Responsible Party): Jeffrey E. Terrell, M.D., University of Michigan

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Chronic Rhinosinusitis
• Interventions: Drug: probiotic containing L.rhamnosus R0011 strain; Other: Placebo
• Enrollment: 77

Participant Flow

Recruitment Details	82 participants were screened . 77 enrolled.
Pre-assignment Details

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
Reason Not Completed
Withdrawal by Subject	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 Number of Baseline Participants		39	38	77
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	39 participants	38 participants	77 participants
		49.4 (12.6)	49.6 (8.6)	49.5 (10)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	39 participants	38 participants	77 participants
	Female	19 48.7%	25 65.8%	44 57.1%
	Male	20 51.3%	13 34.2%	33 42.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	39 participants	38 participants	77 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%	0 0.0%
asthma; Measure Type: Number; Unit of measure: Participants	Number Analyzed	39 participants	38 participants	77 participants
No asthma		14	14	28
intermittent and mild asthma		13	10	23
moderate-severe asthma		12	14	26
aspirin sensitivity; Measure Type: Number; Unit of measure: Participants	Number Analyzed	39 participants	38 participants	77 participants
Aspirin Sensitivity		12	12	24
No aspirin sensitivity		27	26	53
SinoNasal Outcome Test Score (SNOT-20) [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	39 participants	38 participants	77 participants
		36.4 (16.2)	39.5 (19.8)	37.9 (17.9)
		[1] Measure Description: SinoNasal Outcome Test measures symptom severity. It is a summary score, ranging from 0 to 100 with 100 indicating worse symptoms.

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.
Overall Number of Participants Analyzed	37	35
Mean (Standard Deviation); Unit of Measure: units on a scale
	1.8 (12)	5.5 (14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotic, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.23
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	35	37
Measure Type: Number; Unit of Measure: participants
	17	14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Pill, Probiotic
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.31
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	35	37
Mean (Standard Deviation); Unit of Measure: days
	1.9 (5.5)	0.8 (2.7)

4. Secondary Outcome

Title	Mean Number of Days of Steroid Spray Use for Each Group
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	37	35
Mean (Standard Deviation); Unit of Measure: days
	2.8 (7.4)	0.4 (2.2)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
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 (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Active Intervention	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/39 (0.00%)	0/38 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Active Intervention	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	14/39 (35.90%)	17/38 (44.74%)
Gastrointestinal disorders
bloating †	7/39 (17.95%)	9/38 (23.68%)
diarrhea †	8/39 (20.51%)	10/38 (26.32%)
abdominal pain †	7/39 (17.95%)	7/38 (18.42%)
loose stools †	9/39 (23.08%)	8/38 (21.05%)
† Indicates events were collected by systematic assessment

Limitations and 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.

Results Point of Contact

• Name/Title: Jeffrey E. Terrell
• Organization: University of Michigan
• Phone: 734 936 7633
• EMail: terrelj@umich.edu

• Responsible Party: Jeffrey E. Terrell, M.D., University of Michigan
• ClinicalTrials.gov Identifier: NCT00396162
• Other Study ID Numbers: HUM00006212
• First Submitted: November 2, 2006
• First Posted: November 6, 2006
• Results First Submitted: May 28, 2015
• Results First Posted: August 4, 2016
• Last Update Posted: September 20, 2016