Probiotics and Infections in Conscripts in Military Service

• Sponsor: Helsinki University Central Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01651195
• Collaborator: University of Helsinki (Other), Finnish Defense Forces (Other), Finnish Institute for Health and Welfare (Other)
• Enrollment: 983
• Locations: 2
• Arms: 4
• Actual Duration (Months): 47
• Patients Per Site: 491.5
• Patients Per Site Per Month: 10.5

Study Details

Study Description

Brief Summary

The aim was to study whether probiotic intervention has an impact on seasonal occurrence of upper respiratory and gastrointestinal infections in two different conscript groups. In a randomised, double-blinded, placebo controlled study a total of 983 healthy adults were enrolled from two intakes of conscripts. Conscripts were randomised to receive either a probiotic combination of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis ssp. lactis BB12 (BB12) or a control chewing tablet twice daily for 150 days (recruits) or for 90 days (reserve officer candidates). Clinical examinations were carried out and daily symptom diaries were collected. Outcome measures were the number of days with respiratory and gastrointestinal symptoms and symptom incidence, number and duration of infection episodes, number of antibiotic treatments received and number of days out of service because of the infection. Statistically no significant differences were found between the intervention groups either in the risk of symptom incidence or duration. However, probiotic intervention was associated with reduction of specific respiratory infection symptoms in military recruits, but not in reserve officer candidates. Probiotics did not significantly reduce overall respiratory and gastrointestinal infection morbidity.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Tract Infections; Gastrointestinal Diseases; Asthma Exacerbations	Dietary Supplement: Probiotic; Other: Placebo	N/A

Detailed Description

Military conscripts are susceptible to respiratory and gastrointestinal tract infections. In previous studies probiotics have shown potency to reduce upper respiratory and gastrointestinal infections. The aim was to study whether probiotic intervention has an impact on seasonal occurrence of upper respiratory and gastrointestinal infections in two different conscript groups. In a randomised, double-blinded, placebo controlled study a total of 983 healthy adults were enrolled from two intakes of conscripts. Conscripts were randomised to receive either a probiotic combination of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis ssp. lactis BB12 (BB12) or a control chewing tablet twice daily for 150 days (recruits) or for 90 days (reserve officer candidates). Clinical examinations were carried out and daily symptom diaries were collected. Outcome measures were the number of days with respiratory and gastrointestinal symptoms and symptom incidence, number and duration of infection episodes, number of antibiotic treatments received and number of days out of service because of the infection. Statistically no significant differences were found between the intervention groups either in the risk of symptom incidence or duration. However, probiotic intervention was associated with reduction of specific respiratory infection symptoms in military recruits, but not in reserve officer candidates. Probiotics did not significantly reduce overall respiratory and gastrointestinal infection morbidity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 983 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Probiotic and Respiratory and Gastrointestinal Tract Infections in Finnish Military Conscripts - a Randomized and Placebo-controlled Double-blinded Study
• Actual Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Probiotic tablet (military recruits) Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks	Dietary Supplement: Probiotic; Other: Placebo
Placebo Comparator: Placebo tablet (military recruits) Crystalline cellulose 2 x 2, 3 weeks	Dietary Supplement: Probiotic; Other: Placebo
Active Comparator: Probiotic tablet (reserve officer candidates) Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks	Dietary Supplement: Probiotic; Other: Placebo
Placebo Comparator: Placebo tablet (reserve officer candidates) Crystalline cellulose 2 x 2, 3 weeks	Dietary Supplement: Probiotic; Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Sick Days [Through study completion, an average of 4 months]

   The number of sick days with respiratory and gastrointestinal symptoms and symptom incidence. Other outcome measures were the number and duration of infection episodes, the number of antibiotic treatments received, and the number of days out of service due to an infection. Respiratory infection episodes and symptomatic days were counted by the basis of respiratory infection symptoms recorded into the symptom diary and from the medical visits to health care centers. If the conscript showed minimum of two RTI symptoms for a period of one day or one RTI symptom for a period of two days a RTI episode was considered to be present. Between two episodes a minimum of seven days of non-symptomatic period should be experienced if to be considered as two separate infections. If there were less non-symptomatic days, it was considered to be a continuation of the same infection episode. Symptomatic days were days when at least one symptom was experienced.

Secondary Outcome Measures

1. Number and Duration of Infection Episodes [Through study completion, an average of 4 months]

   Respiratory infection episodes and symptomatic days were counted by the basis of respiratory infection symptoms recorded into the symptom diary and from the medical visits to health care centers.

2. Number of Antibiotic Treatments Received [Through study completion, an average of 4 months]

   Number of antibiotic treatments received were collected during the medical visits.

3. Number of Days Out of Service Due to an Infection [Through study completion, an average of 4 months]

   If the conscript showed minimum of two RTI symptoms for a period of one day or one RTI symptom for a period of two days a RTI episode was considered to be present. Between two episodes a minimum of seven days of non-symptomatic period should be experienced if to be considered as two separate infections. If there were less non-symptomatic days, it was considered to be a continuation of the same infection episode. Symptomatic days were days when at least one symptom was experienced. Gastrointestinal tract infection episodes and symptom days were calculated in the same fashion except 14 non symptomatic days should be in between the two to be considered as two different episodes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy adults attending military service in July 2012 and healthy adults attending reserve office school in October 2012

Exclusion Criteria:

• Regular use of oral corticosteroids

• Regular consumption (over 3 times a week) of probiotic bacteria containing products 3 weeks before intervention

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Finnish Defence Forces	Hamina		Finland
2	The Finnish Defence Forces	Upinniemi		Finland

Sponsors and Collaborators

• Helsinki University Central Hospital
• University of Helsinki
• Finnish Defense Forces
• Finnish Institute for Health and Welfare

Investigators

• Principal Investigator: Anne I Pitkäranta, md, Chief Physician

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anne pitkäranta, Professor/Chief Physician at Hospital District of Helsinki and Uusimaa, Helsinki University Central Hospital
• ClinicalTrials.gov Identifier: NCT01651195
• Other Study ID Numbers: 189/13/03/00/11
• First Posted: Jul 26, 2012
• Last Update Posted: Jun 14, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections; Communicable Diseases; Respiratory Tract Infections; Gastrointestinal Diseases; Digestive System Diseases

Study Results

Participant Flow

Pre-assignment Detail

Sample size was calculated on the assumption that the use of probiotic would result in a 17% reduction in the number of sick days estimated that, with a power of 85% and at a significance level of 0.05 (Power 0.85, ß=0.15000 and α=0.05), we needed 300 conscripts per group to show a 17% difference between the groups. Each conscript was randomly allocated to the probiotic or the control group according to a computer generated, 8-blocked randomization list.

Arm/Group Title	Probiotic Tablet (Military Recruits)	Placebo Tablet (Military Recruits)	Probiotic Tablet (Reserve Officer Candidates)	Placebo Tablet (Reserve Officer Candidates)
Arm/Group Description	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Chrystalline celluloce 2 x 2, 3 weeks Placebo	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Chrystalline celluloce 2 x 2, 3 weeks Placebo
Period Title: Overall Study
STARTED	284	284	204	211
COMPLETED	63	73	121	103
NOT COMPLETED	221	211	83	108

Baseline Characteristics

Arm/Group Title	Probiotic Tablet (Military Recruits)	Placebo Tablet (Military Recruits)	Probiotic Tablet (Reserve Officer Candidates)	Placebo Tablet (Reserve Officer Candidates)	Total
Arm/Group Description	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Chrystalline celluloce 2 x 2, 3 weeks Placebo	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Chrystalline celluloce 2 x 2, 3 weeks Placebo	Total of all reporting groups
Overall Participants	284	284	204	211	983
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	284 100%	284 100%	204 100%	211 100%	983 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	284 100%	284 100%	204 100%	211 100%	983 100%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Finland	284 100%	284 100%	204 100%	211 100%	983 100%

Outcome Measures

1. Primary Outcome

Title	Number of Sick Days
Description	The number of sick days with respiratory and gastrointestinal symptoms and symptom incidence. Other outcome measures were the number and duration of infection episodes, the number of antibiotic treatments received, and the number of days out of service due to an infection. Respiratory infection episodes and symptomatic days were counted by the basis of respiratory infection symptoms recorded into the symptom diary and from the medical visits to health care centers. If the conscript showed minimum of two RTI symptoms for a period of one day or one RTI symptom for a period of two days a RTI episode was considered to be present. Between two episodes a minimum of seven days of non-symptomatic period should be experienced if to be considered as two separate infections. If there were less non-symptomatic days, it was considered to be a continuation of the same infection episode. Symptomatic days were days when at least one symptom was experienced.
Time Frame	Through study completion, an average of 4 months

Outcome Measure Data

Analysis Population Description

According to the study nurse, the file containing number of sick days data of this particular study is no more available.

Arm/Group Title	Probiotic Tablet (Military Recruits)	Placebo Tablet (Military Recruits)	Probiotic Tablet (Reserve Officer Candidates)	Placebo Tablet (Reserve Officer Candidates)
Arm/Group Description	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks	Crystalline cellulose 2 x 2, 3 weeks	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks	Crystalline cellulose 2 x 2, 3 weeks
Measure Participants	0	0	0	0
Measure Days	0	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotic Tablet (Military Recruits), Placebo Tablet (Military Recruits), Probiotic Tablet (Reserve Officer Candidates), Placebo Tablet (Reserve Officer Candidates)
	Comments
	Type of Statistical Test	Superiority
	Comments	We estimated that, with a power of 85% and at a significance level of 0.05 (Power 0.85, ß=0.14990 and α=0.05), we needed 467 conscripts per group to show a 17% difference between the groups. Each conscript was randomly allocated to the probiotic or the control group according to a computer generated, 8-blocked randomization list.
Statistical Test of Hypothesis	p-Value	< 0.05
	Comments
	Method	Fisher Exact
	Comments
Other Statistical Analysis		Result variables were analyzed according to "intention to treat" (ITT) principle. Missing data was handled by statistic modeling. Data on symptom diaries were calculated as follows: the incidence and duration of individual infection symptoms and respiratory episodes were analyzed between the intervention groups using time to event analysis (cox model for hazard) and duration analysis (gamma regression model). The results are expressed as a hazard ratio (incidence rate ratio) of symptoms and the mean duration of symptoms (days) with 95% confidence intervals or standard deviations. The sums of respiratory and gastrointestinal symptoms were calculated with gamma regression analysis.

2. Secondary Outcome

Title	Number and Duration of Infection Episodes
Description	Respiratory infection episodes and symptomatic days were counted by the basis of respiratory infection symptoms recorded into the symptom diary and from the medical visits to health care centers.
Time Frame	Through study completion, an average of 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Probiotic Tablet (Military Recruits)	Placebo Tablet (Military Recruits)	Probiotic Tablet (Reserve Officer Candidates)	Placebo Tablet (Reserve Officer Candidates)
Arm/Group Description	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Crystalline cellulose 2 x 2, 3 weeks Placebo	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Crystalline cellulose 2 x 2, 3 weeks Placebo
Measure Participants	284	284	204	211
Measure Episodes	411	402	56	101
Count of Units [Episodes]	33	35	30	29

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotic Tablet (Military Recruits), Placebo Tablet (Military Recruits), Probiotic Tablet (Reserve Officer Candidates), Placebo Tablet (Reserve Officer Candidates)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.05
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Number of Antibiotic Treatments Received
Description	Number of antibiotic treatments received were collected during the medical visits.
Time Frame	Through study completion, an average of 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Probiotic Tablet (Military Recruits)	Placebo Tablet (Military Recruits)	Probiotic Tablet (Reserve Officer Candidates)	Placebo Tablet (Reserve Officer Candidates)
Arm/Group Description	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Crystalline cellulose 2 x 2, 3 weeks Placebo	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Crystalline cellulose 2 x 2, 3 weeks Placebo
Measure Participants	284	284	204	211
Measure Treatments	91	88	17	31
Count of Units [Treatments]	15	23	2	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotic Tablet (Military Recruits), Placebo Tablet (Military Recruits), Probiotic Tablet (Reserve Officer Candidates), Placebo Tablet (Reserve Officer Candidates)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.05
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Number of Days Out of Service Due to an Infection
Description	If the conscript showed minimum of two RTI symptoms for a period of one day or one RTI symptom for a period of two days a RTI episode was considered to be present. Between two episodes a minimum of seven days of non-symptomatic period should be experienced if to be considered as two separate infections. If there were less non-symptomatic days, it was considered to be a continuation of the same infection episode. Symptomatic days were days when at least one symptom was experienced. Gastrointestinal tract infection episodes and symptom days were calculated in the same fashion except 14 non symptomatic days should be in between the two to be considered as two different episodes.
Time Frame	Through study completion, an average of 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Probiotic Tablet (Military Recruits)	Placebo Tablet (Military Recruits)	Probiotic Tablet (Reserve Officer Candidates)	Placebo Tablet (Reserve Officer Candidates)
Arm/Group Description	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Crystalline cellulose 2 x 2, 3 weeks Placebo	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic	Crystalline cellulose 2 x 2, 3 weeks Placebo
Measure Participants	284	284	204	211
Measure Days	150	150	90	90
Count of Units [Days]	44	41	4	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotic Tablet (Military Recruits), Placebo Tablet (Military Recruits), Probiotic Tablet (Reserve Officer Candidates), Placebo Tablet (Reserve Officer Candidates)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.05
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Arm/Group Title	Probiotic Tablet (Military Recruits)		Placebo Tablet (Military Recruits)		Probiotic Tablet (Reserve Officer Candidates)		Placebo Tablet (Reserve Officer Candidates)
Arm/Group Description	Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic		Chrystalline celluloce 2 x 2, 3 weeks Placebo		Lactobacillus rhamnosus 8-9 x 10 -9 2 x 2 3 weeks Probiotic		Chrystalline celluloce 2 x 2, 3 weeks Placebo
All Cause Mortality
	Probiotic Tablet (Military Recruits)		Placebo Tablet (Military Recruits)		Probiotic Tablet (Reserve Officer Candidates)		Placebo Tablet (Reserve Officer Candidates)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/284 (0%)		0/284 (0%)		0/204 (0%)		0/211 (0%)
Serious Adverse Events
	Probiotic Tablet (Military Recruits)		Placebo Tablet (Military Recruits)		Probiotic Tablet (Reserve Officer Candidates)		Placebo Tablet (Reserve Officer Candidates)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/284 (0%)		0/284 (0%)		0/204 (0%)		0/211 (0%)
Other (Not Including Serious) Adverse Events
	Probiotic Tablet (Military Recruits)		Placebo Tablet (Military Recruits)		Probiotic Tablet (Reserve Officer Candidates)		Placebo Tablet (Reserve Officer Candidates)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/284 (0%)		0/284 (0%)		0/204 (0%)		0/211 (0%)

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.