Effect of Probiotic on the Innate and Adaptive Host Response to Rhinovirus (EPIARR)

• Sponsor: University of Virginia (Other)
• Overall Status: Completed
• CT.gov ID: NCT01669603
• Collaborator: DuPont Nutrition and Health (Industry)
• Enrollment: 789
• Location: 1
• Arms: 2
• Duration (Months): 46
• Patients Per Site Per Month: 17.2

Study Details

Study Description

Brief Summary

The study is designed to assess the effect of ingestion of a probiotic on innate and adaptive host responses to rhinovirus infection.

Condition or Disease	Intervention/Treatment	Phase
Common Cold	Dietary Supplement: Bifidobacterium lactis Bl-04; Dietary Supplement: Placebo; Biological: Rhinovirus	N/A

Detailed Description

The common cold is a ubiquitous illness of man that is associated with significant medical and socioeconomic consequences. Current treatments for the common cold that have proven efficacy are limited to pharmacologic agents that are directed at specific symptoms. These treatments- antihistamines, nasal decongestants and analgesics- have limited effectiveness, generally relieving the target symptom by 15-25% at the peak of activity, and are associated with bothersome side effects. There are no currently effective treatments for prevention of rhinovirus infections.

Probiotics have been defined by FAO/WHO as "Live microorganisms which when administered in adequate amount confer a health benefit on a host." The most common probiotics belong to Lactobacillus or Bifidobacterium genera. Bifidobacteria are natural human gut inhabitants that were discovered over a hundred years ago from the feces of breast-fed infants. The study product Bifidobacterium animalis subspecies (subsp.) lactis Bl-04 (Bl-04) has been genetically characterized as B. animalis subsp. lactis by 16S rRNA gene sequencing and full genome sequence comparison. Bl-04 has been deposited in the American Type Culture Collections safe deposit as SD5219.

This study will test the hypothesis that ingestion of a probiotic Bifidobacterium animalis subsp. lactis Bl-04 will alter the innate and adaptive host response to rhinovirus infection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 789 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Effect of Probiotic on the Innate and Adaptive Host Response to Rhinovirus (EPIARR)
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bifidobacterium animalis lactis Bl-04 Bifidobacterium animalis subspecies lactis Bl-04 as powder mixed into drink.	Dietary Supplement: Bifidobacterium lactis Bl-04; The study product will be a 2*109 cfus of probiotic Bifidobacterium lactis Bl-04 mixed with 1g of sucrose as a carrier.; Biological: Rhinovirus; rhinovirus for experimental challenge
Placebo Comparator: Placebo Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product.	Dietary Supplement: Placebo; Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product.; Biological: Rhinovirus; rhinovirus for experimental challenge

Outcome Measures

Primary Outcome Measures

1. Interleukin-8 (IL-8) [72 hours]

   Nasal lavage will be performed to collect and measure IL-8.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

AT ENROLLMENT:

• Subject must be 18-60 years of age.

• Subject must read and sign a copy of the approved Consent Form

• Female subjects must be using an effective birth control method.

INCLUSION CRITERIA AT DAY -28

• Subject must read and sign a copy of the approved Consent Form

AT CHALLENGE:

• Female subjects must be using an effective birth control method.

• Subject must have a serum neutralizing antibody titer of less than or equal to 1:4 to rhinovirus type 39

Exclusion Criteria:

AT ENROLLMENT:

• Current cancer diagnosis or immunosuppressive therapy in the last 6 months

• Any clinically significant abnormalities of the upper respiratory tract

• Any clinically significant acute or chronic respiratory illness

• Any clinically significant bleeding tendency by history

• Hypertension that requires treatment with antihypertensive medications

• History of angina or other clinically significant cardiac disease

• Any medical condition that in the opinion of the Principal Investigator is cause for exclusion from the study

• History of regular use (more than 3 days in 7) of tobacco products within the preceding two weeks

• History of drug or alcohol abuse in the 6 months preceding the study

EXCLUSION CRITERIA AT DAY -28

• Antibiotic use within 3 months prior to study start

• Female subjects with a positive urine pregnancy screen.

• History of use of probiotics in the preceding 2 weeks.

EXCLUSION CRITERIA AT CHALLENGE:

• Any upper respiratory infection or allergic rhinitis in the two weeks prior to the start of the study

• Any medical condition that in the opinion of the Principal Investigator is cause for exclusion from the study

• Use of any anti-inflammatory (steroids or NSAIDs) or cough/cold preparation in the two weeks prior to the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Virginia	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• University of Virginia
• DuPont Nutrition and Health

Investigators

• Principal Investigator: Ronald Turner, MD, University of Virginia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ronald Turner, MD, Principal Investigator, University of Virginia
• ClinicalTrials.gov Identifier: NCT01669603
• Other Study ID Numbers: 16241
• First Posted: Aug 21, 2012
• Last Update Posted: Apr 25, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Ronald Turner, MD, Principal Investigator, University of Virginia: Common cold
• Additional relevant MeSH terms: Common Cold

Study Results

Participant Flow

Pre-assignment Detail	789 subjects were screened for participation. 190 subjects met all study criteria for randomization to study intervention.

Arm/Group Title	Bifidobacterium Animalis Lactis Bl-04	Placebo
Arm/Group Description	Bifidobacterium animalis subspecies lactis Bl-04 as powder mixed into drink. Bifidobacterium lactis Bl-04: The study product will be a 2*109 cfus of probiotic Bifidobacterium lactis Bl-04 mixed with 1g of sucrose as a carrier.	Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product. Placebo: Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product.
Period Title: Overall Study
STARTED	95	95
COMPLETED	58	57
NOT COMPLETED	37	38

Baseline Characteristics

Arm/Group Title	Bifidobacterium Animalis Lactis Bl-04	Placebo	Total
Arm/Group Description	Bifidobacterium animalis subspecies lactis Bl-04 as powder mixed into drink. Bifidobacterium lactis Bl-04: The study product will be a 2*109 cfus of probiotic Bifidobacterium lactis Bl-04 mixed with 1g of sucrose as a carrier.	Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product. Placebo: Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product.	Total of all reporting groups
Overall Participants	95	95	190
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	58 61.1%	57 60%	115 60.5%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22 (6)	23 (7)	23 (7)
Sex: Female, Male (Count of Participants)
Female	39 41.1%	33 34.7%	72 37.9%
Male	19 20%	24 25.3%	43 22.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 3.2%	4 4.2%	7 3.7%
Not Hispanic or Latino	54 56.8%	52 54.7%	106 55.8%
Unknown or Not Reported	1 1.1%	1 1.1%	2 1.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2.1%	8 8.4%	10 5.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 3.2%	2 2.1%	5 2.6%
White	52 54.7%	46 48.4%	98 51.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.1%	1 1.1%	2 1.1%
Region of Enrollment (participants) [Number]
United States	95 100%	95 100%	190 100%

Outcome Measures

1. Primary Outcome

Title	Interleukin-8 (IL-8)
Description	Nasal lavage will be performed to collect and measure IL-8.
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

analysis cohort was those volunteers who were susceptible to RV-A39 by neutralizing antibody titer, had no virus detected in the nasal lavage on day 0, and who were infected and completed the study

Arm/Group Title	Bifidobacterium Animalis Lactis Bl-04	Placebo
Arm/Group Description	Bifidobacterium animalis subspecies lactis Bl-04 as powder mixed into drink. Bifidobacterium lactis Bl-04: The study product will be a 2*109 cfus of probiotic Bifidobacterium lactis Bl-04 mixed with 1g of sucrose as a carrier.	Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product. Placebo: Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product.
Measure Participants	58	57
Geometric Mean (Standard Deviation) [pg/ml]	133 (2.5)	122 (2.9)

Adverse Events

Time Frame	7 weeks
Arm/Group Title	Bifidobacterium Animalis Lactis Bl-04		Placebo
Arm/Group Description	Bifidobacterium animalis subspecies lactis Bl-04 as powder mixed into drink. Bifidobacterium lactis Bl-04: The study product will be a 2*109 cfus of probiotic Bifidobacterium lactis Bl-04 mixed with 1g of sucrose as a carrier.		Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product. Placebo: Placebo will be 1g of sucrose that has identical appearance, smell, and taste with the study product.
All Cause Mortality
	Bifidobacterium Animalis Lactis Bl-04		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bifidobacterium Animalis Lactis Bl-04		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/95 (0%)		0/95 (0%)
Other (Not Including Serious) Adverse Events
	Bifidobacterium Animalis Lactis Bl-04		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/95 (4.2%)		1/95 (1.1%)
Gastrointestinal disorders
gastrointestinal	4/95 (4.2%)	4	0/95 (0%)	0
Respiratory, thoracic and mediastinal disorders
respiratory	0/95 (0%)	0	1/95 (1.1%)	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.