Trial Outcomes & Findings for Impact of Probiotics for Reducing Infections in Veterans: The IMPROVE Study (NCT NCT01321606)
NCT ID: NCT01321606
Last Updated: 2018-08-03
Results Overview
Participants in the final outcome may be colonized at both GI and Extra-GI sites, thus the total numbers from the outcome cells can be greater than the overall number of participants analyzed.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
113 participants
Primary outcome timeframe
4 weeks
Results posted on
2018-08-03
Participant Flow
Participant milestones
| Measure |
Arm 1a: Extra-GI Probiotic
Subjects with Extra-GI colonization at initial screening who were randomized to probiotic treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks.
|
Arm 2a: Extra-GI Placebo
Subjects with Extra-GI colonization at initial screening who were randomized to placebo treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
Arm 1b: GI Probiotic
Subjects with GI colonization at initial screening who were randomized to probiotic treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
|
Arm 2b: GI Placebo
Subjects with GI colonization at initial screening who were randomized to placebo treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
18
|
32
|
34
|
29
|
|
Overall Study
COMPLETED
|
18
|
32
|
34
|
28
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Arm 1a: Extra-GI Probiotic
Subjects with Extra-GI colonization at initial screening who were randomized to probiotic treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks.
|
Arm 2a: Extra-GI Placebo
Subjects with Extra-GI colonization at initial screening who were randomized to placebo treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
Arm 1b: GI Probiotic
Subjects with GI colonization at initial screening who were randomized to probiotic treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
|
Arm 2b: GI Placebo
Subjects with GI colonization at initial screening who were randomized to placebo treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Impact of Probiotics for Reducing Infections in Veterans: The IMPROVE Study
Baseline characteristics by cohort
| Measure |
Arm 1: Probiotic
n=52 Participants
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
Lactobacillus rhamnosus HN001: Subjects will be given a pill formulation of a probiotic L. rhamnosus HN001 to be taken once a day, at a dose of 1 x 10\^10 organisms
|
Arm 2: Placebo
n=61 Participants
Placebo composed of identical inactive components to the active product, to be taken once daily for 4 weeks.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
Total
n=113 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.4 years
STANDARD_DEVIATION 14.7 • n=5 Participants
|
62.9 years
STANDARD_DEVIATION 12.6 • n=7 Participants
|
63.6 years
STANDARD_DEVIATION 13.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
49 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
105 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 4 weeksParticipants in the final outcome may be colonized at both GI and Extra-GI sites, thus the total numbers from the outcome cells can be greater than the overall number of participants analyzed.
Outcome measures
| Measure |
Arm 1a: Extra-GI Probiotic
n=18 Participants
Subjects with Extra-GI colonization at initial screening who were randomized to probiotic treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
|
Arm 2a: Extra-GI Placebo
n=32 Participants
Subjects with Extra-GI colonization at initial screening who were randomized to placebo treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
Arm 1b: GI Probiotic
n=34 Participants
Subjects with GI colonization at initial screening who were randomized to probiotic treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
|
Arm 2b: GI Placebo
n=29 Participants
Subjects with GI colonization at initial screening who were randomized to placebo treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
|---|---|---|---|---|
|
Oral L. Rhamnosus HN001 Therapy Compared to Placebo on Gastrointestinal and Extra-gastrointestinal Colonization of S. Aureus.
Endpoint GI colonization
|
9 Participants
|
17 Participants
|
25 Participants
|
24 Participants
|
|
Oral L. Rhamnosus HN001 Therapy Compared to Placebo on Gastrointestinal and Extra-gastrointestinal Colonization of S. Aureus.
Endpoint Extra-GI colonization
|
16 Participants
|
22 Participants
|
20 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Some participants were excluded from this analysis due to lack of sample collection, or unusable results because tests did not meet acceptability criteria.
This outcome is the mean difference in the % of granulocytes that phagocytized E. coli, from blood samples taken at the beginning and end of the trial. Percent of granulocytes phagocytizing E. coli at baseline is subtracted by percent of granulocytes phagocytizing E. coli at the end of the trial. The mean and standard error are calculated and reported for each study arm. This result
Outcome measures
| Measure |
Arm 1a: Extra-GI Probiotic
n=15 Participants
Subjects with Extra-GI colonization at initial screening who were randomized to probiotic treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
|
Arm 2a: Extra-GI Placebo
n=25 Participants
Subjects with Extra-GI colonization at initial screening who were randomized to placebo treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
Arm 1b: GI Probiotic
n=27 Participants
Subjects with GI colonization at initial screening who were randomized to probiotic treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
|
Arm 2b: GI Placebo
n=21 Participants
Subjects with GI colonization at initial screening who were randomized to placebo treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
|---|---|---|---|---|
|
Oral L. Rhamnosus HN001 Therapy Compared With Placebo on Phagocytic Functioning of Polymorphonuclear (PMN) and Monocyte Cells
|
-0.29 Difference in % POS of Granulocytes
Standard Error 2.43
|
-1.38 Difference in % POS of Granulocytes
Standard Error 2.65
|
1.23 Difference in % POS of Granulocytes
Standard Error 2.42
|
2.61 Difference in % POS of Granulocytes
Standard Error 2.83
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Some participants were excluded from this analysis due to lack of sample collection, or unusable results because tests did not meet acceptability criteria.
This outcome is the mean difference in the % of monocytes that phagocytized E. coli, from blood samples taken at the beginning and end of the trial. Percent of monocytes phagocytizing E. coli at baseline is subtracted by percent of monocytes phagocytizing E. coli at the end of the trial. The mean and standard error are calculated and reported for each study arm.
Outcome measures
| Measure |
Arm 1a: Extra-GI Probiotic
n=15 Participants
Subjects with Extra-GI colonization at initial screening who were randomized to probiotic treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
|
Arm 2a: Extra-GI Placebo
n=25 Participants
Subjects with Extra-GI colonization at initial screening who were randomized to placebo treatment.
Extra-GI colonization was defined as a positive PCR result for S. aureus from any swab of the nares, axillae or wound, with no positive result from swabs of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
Arm 1b: GI Probiotic
n=27 Participants
Subjects with GI colonization at initial screening who were randomized to probiotic treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
|
Arm 2b: GI Placebo
n=21 Participants
Subjects with GI colonization at initial screening who were randomized to placebo treatment.
GI colonization was defined as a positive PCR result for S. aureus from any swab of the oropharynx, or peri-rectum.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
|---|---|---|---|---|
|
Oral L. Rhamnosus HN001 Therapy Compared With Placebo on Phagocytic Functioning of Polymorphonuclear (PMN) and Monocyte Cells
|
-0.54 Difference in % POS of Monocytes
Standard Error 0.29
|
0.59 Difference in % POS of Monocytes
Standard Error 0.32
|
0.07 Difference in % POS of Monocytes
Standard Error 0.33
|
0.15 Difference in % POS of Monocytes
Standard Error 0.36
|
Adverse Events
Arm 1: Extra-GI Probiotic
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Arm 2: Extra-GI Placebo
Serious events: 2 serious events
Other events: 17 other events
Deaths: 0 deaths
Arm 3: GI Probiotic
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Arm 4: GI Placebo
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm 1: Extra-GI Probiotic
n=18 participants at risk
Subjects with Extra-GI colonization at initial screening who were randomized to probiotic treatment. Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
Lactobacillus rhamnosus HN001: Subjects will be given a pill formulation of a probiotic L. rhamnosus HN001 to be taken once a day, at a dose of 1 x 10\^10 organisms
|
Arm 2: Extra-GI Placebo
n=32 participants at risk
Subjects with Extra-GI colonization at initial screening who were randomized to placebo treatment. Placebo composed of identical inactive components to the active product, to be taken once daily for 4 weeks.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
Arm 3: GI Probiotic
n=34 participants at risk
Subjects with GI colonization at initial screening who were randomized to probiotic treatment. Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
Lactobacillus rhamnosus HN001: Subjects will be given a pill formulation of a probiotic L. rhamnosus HN001 to be taken once a day, at a dose of 1 x 10\^10 organisms
|
Arm 4: GI Placebo
n=29 participants at risk
Subjects with GI colonization at initial screening who were randomized to placebo treatment. Placebo composed of identical inactive components to the active product, to be taken once daily for 4 weeks.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
|---|---|---|---|---|
|
Cardiac disorders
Cardiovascular event
|
0.00%
0/18 • 4 weeks
|
6.2%
2/32 • Number of events 2 • 4 weeks
|
0.00%
0/34 • 4 weeks
|
0.00%
0/29 • 4 weeks
|
Other adverse events
| Measure |
Arm 1: Extra-GI Probiotic
n=18 participants at risk
Subjects with Extra-GI colonization at initial screening who were randomized to probiotic treatment. Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
Lactobacillus rhamnosus HN001: Subjects will be given a pill formulation of a probiotic L. rhamnosus HN001 to be taken once a day, at a dose of 1 x 10\^10 organisms
|
Arm 2: Extra-GI Placebo
n=32 participants at risk
Subjects with Extra-GI colonization at initial screening who were randomized to placebo treatment. Placebo composed of identical inactive components to the active product, to be taken once daily for 4 weeks.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
Arm 3: GI Probiotic
n=34 participants at risk
Subjects with GI colonization at initial screening who were randomized to probiotic treatment. Subjects were given a capsule formulation of a 1x10\^10 colony-forming units of probiotic L. rhamnosus HN001 to be taken once a day, for 4 weeks
Lactobacillus rhamnosus HN001: Subjects will be given a pill formulation of a probiotic L. rhamnosus HN001 to be taken once a day, at a dose of 1 x 10\^10 organisms
|
Arm 4: GI Placebo
n=29 participants at risk
Subjects with GI colonization at initial screening who were randomized to placebo treatment. Placebo composed of identical inactive components to the active product, to be taken once daily for 4 weeks.
Placebo pill: composed of identical inactive components to the active product, given to be taken once daily for 4 weeks.
|
|---|---|---|---|---|
|
General disorders
Fever
|
0.00%
0/18 • 4 weeks
|
6.2%
2/32 • 4 weeks
|
2.9%
1/34 • 4 weeks
|
3.4%
1/29 • 4 weeks
|
|
Gastrointestinal disorders
Nausea/Vomiting
|
16.7%
3/18 • 4 weeks
|
15.6%
5/32 • 4 weeks
|
11.8%
4/34 • 4 weeks
|
6.9%
2/29 • 4 weeks
|
|
Gastrointestinal disorders
Constipation
|
22.2%
4/18 • 4 weeks
|
6.2%
2/32 • 4 weeks
|
0.00%
0/34 • 4 weeks
|
3.4%
1/29 • 4 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough/Cold/Congestion
|
5.6%
1/18 • 4 weeks
|
15.6%
5/32 • 4 weeks
|
8.8%
3/34 • 4 weeks
|
20.7%
6/29 • 4 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle Pain/Cramp/Spasm
|
16.7%
3/18 • 4 weeks
|
15.6%
5/32 • 4 weeks
|
32.4%
11/34 • 4 weeks
|
13.8%
4/29 • 4 weeks
|
|
Gastrointestinal disorders
Upset Stomach/Heartburn
|
5.6%
1/18 • 4 weeks
|
3.1%
1/32 • 4 weeks
|
2.9%
1/34 • 4 weeks
|
3.4%
1/29 • 4 weeks
|
|
Gastrointestinal disorders
Gas/Bloating
|
11.1%
2/18 • 4 weeks
|
3.1%
1/32 • 4 weeks
|
2.9%
1/34 • 4 weeks
|
3.4%
1/29 • 4 weeks
|
|
Gastrointestinal disorders
Unusual Stool
|
11.1%
2/18 • 4 weeks
|
25.0%
8/32 • 4 weeks
|
20.6%
7/34 • 4 weeks
|
17.2%
5/29 • 4 weeks
|
|
General disorders
Bad Taste
|
0.00%
0/18 • 4 weeks
|
6.2%
2/32 • 4 weeks
|
0.00%
0/34 • 4 weeks
|
3.4%
1/29 • 4 weeks
|
|
Skin and subcutaneous tissue disorders
Itchiness
|
0.00%
0/18 • 4 weeks
|
0.00%
0/32 • 4 weeks
|
0.00%
0/34 • 4 weeks
|
6.9%
2/29 • 4 weeks
|
Additional Information
Dr. Nasia Sardar
William S. Middleton Memorial Veterans Affairs Medical Center
Phone: 608-256-1901
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place