Use of a Novel Synbiotic to Change Human Gut Bacteria and Improve Health in Obese Adults
Sponsor
Rush University Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT02355210
Collaborator
University of Nebraska Lincoln (Other), University of Alberta (Other)
151
1
6
28
5.4
Study Details
Study Description
Brief Summary
This study evaluates the effect of a dietary supplement to improve gut health. The participants will take one of six dietary treatments for three weeks, and the gut bacteria and the gut intestinal barrier will be assessed to determine if these dietary treatments beneficially change these markers of gut health.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
In this study, we intend to test the ecological and therapeutic functionality of a synbiotic combination of a Bifidobacterium adolescentis strain and the prebiotic galactooligosaccharide (GOS) in a human clinical trial. The synbiotic combination was selected based on a novel in vivo selection; specifically, the strain (BD1) is an human autochthonous gut organism that was enriched in an individual by GOS. Our experiments will test the efficacy of this synbiotic compared to a conventional synbiotic. We hypothesize this rationally selected synbiotic will improve intestinal barrier function in obese adult subjects, thereby preventing endotoxemia and metabolic inflammation, physiologically relevant functions that are increased in obese individuals. Our objectives are to: (1) compare the ability of the test and control synbiotic preparations to alter the gut microbiota in obese individuals; (2) test if GOS supports colonization and metabolic activity of test and control strains in the human gut; (3) compare the ability of the two synbiotic preparations to improve intestinal permeability and endotoxemia in obese subjects; and (4) assess associations between the gut microbiota and the test strain with biomarkers for translocation and endotoxemia.
Study Design
Study Type:
Interventional
Actual Enrollment
:
151 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Application of a Novel Synbiotic to Modulate the Human Gut Microbiota and Improve Health
Study Start Date
:
Jun 1, 2013
Actual Primary Completion Date
:
Aug 1, 2015
Actual Study Completion Date
:
Oct 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo 5 g lactose given as a placebo |
Dietary Supplement: Placebo
lactose powder, 5 grams
|
| Experimental: Probiotic 1 Bifidobacteria adolescentis BD1, 10^9 |
Dietary Supplement: Bifidobacteria adolescentis BD1
packet containing 10^9 cells of Bifidobacteria adolescentis BD1
|
| Experimental: Probiotic 2 Bifidobacteria animalis subsp. lactis BB-12, 10^9 |
Dietary Supplement: Bifidobacteria animalis subsp. lactis BB-12
packet containing 10^9 cells of Bifidobacteria animalis subsp. lactis BB-12
|
| Experimental: Prebiotic galactooligosaccaride, 5 g |
Dietary Supplement: galactooligosaccharide
5 g galactooligosaccharide
|
| Experimental: Synbiotic 1 galacto-oligosaccharide (5 g) and Bifidobacteria adolescentis BD1 (10^9) |
Dietary Supplement: Bifidobacteria adolescentis BD1 and galactooligosaccharide
packet containing 10^9 cells Bifidobacteria adolescentis BD1 and 5 g galactooligosaccharide
|
| Experimental: Synbiotic 2 galacto-oligosaccharide (5 g) and Bifidobacteria animalis subsp. lactis BB-12 (10^9) |
Dietary Supplement: Bifidobacteria animalis subsp. lactis BB-12 and galactooligosaccharide
packet containing 10^9 cells B animalis subsp. lactis BB-12 and 5 g galactooligosaccharide
|
Outcome Measures
Primary Outcome Measures
- Change in Microbiota, as Measured by Change in Microbiota Composition, Including Presence of B. Adolescentis BD1 and B. Animalis Supsp Lactis BB-12 [baseline and three weeks]
change in microbiota composition, including presence of B. adolescentis BD1 and B. animalis supsp lactis BB-12
- Change in Intestinal Permeability as Measured by Change in Percent Sugars in Urine [baseline and three weeks]
Change in intestinal permeability as measured by change in percent sugars in urine
Secondary Outcome Measures
- Endotoxemia, as Measured by Change in Circulating Endotoxin by Lipopolysaccharide and Lipopolysaccharide-binding Protein [baseline and three weeks]
Endotoxemia, as measured by change in circulating endotoxin by lipopolysaccharide and lipopolysaccharide-binding protein
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
- 18-65 yrs, obese (30 kg/m2 and greater)
Exclusion Criteria:
- (1) prior intestinal resection, (2) patient history of GI diseases except for hiatal hernia, GERD, hemorrhoids, (3) severe renal disease defined by creatinine more than twice normal, (4) markedly abnormal liver function defined by ALT/AST over 4 times normal levels or elevated bilirubin (5) antibiotic use within the last 12 weeks prior to enrollment, (6) lean or overweight (BMI < 30 kg/m2), (7) intolerant to aspirin, (8) regular use of aspirin, (9) excessive alcohol intake (>2 drinks for men, 1 drink for women daily), (10) presence of uncontrolled chronic metabolic disease (cardiovascular disease, insulin requiring diabetes or uncontrolled diabetes, cancer, etc, (11) a plan to have a major change in dietary habit during the following 6 months, (12) consumption of probiotics, prebiotics or synbiotics without an appropriate 4 week washout period, (13) lactose intolerance or malabsorption; (14) subjects younger than 18 or older than 65, (15) unwillingness to consent to the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
Sponsors and Collaborators
- Rush University Medical Center
- University of Nebraska Lincoln
- University of Alberta
Investigators
- Principal Investigator: Robert Hutkins, PhD, University of Nebraska Lincoln
- Principal Investigator: Jens Walter, PhD, University of Alberta
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Rush University Medical Center
ClinicalTrials.gov Identifier:
NCT02355210
Other Study ID Numbers:
- USDA-NIFA-AFRI-003397
First Posted:
Feb 4, 2015
Last Update Posted:
Nov 23, 2021
Last Verified:
Nov 1, 2021
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 151 subjects enrolled. Of these, 37 subjects discontinued trial prior to treatment randomization due to loss to follow-up (n=12), subject no longer interested (n=9), laboratory values outside range (n=5), and other (n=11). |
| Arm/Group Title | Placebo | Probiotic 1 | Probiotic 2 | Synbiotic 1 | Synbiotic 2 | Prebiotic |
|---|---|---|---|---|---|---|
| Arm/Group Description | 5 g lactose given as a placebo | Bifidobacteria adolescentis BD1, 10^9 | Bifidobacteria animalis subsp. lactis BB-12, 10^9 | galacto-oligosaccharide (5 g) and Bifidobacteria adolescentis BD1 (10^9) | galacto-oligosaccharide (5 g) and Bifidobacteria animalis subsp. lactis BB-12 (10^9) | galactooligosaccharide, 5 g |
| Period Title: Overall Study | ||||||
| STARTED | 19 | 18 | 16 | 17 | 19 | 18 |
| COMPLETED | 19 | 18 | 16 | 17 | 19 | 18 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo | Probiotic 1 | Probiotic 2 | Synbiotic 1 | Synbiotic 2 | Prebiotic | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 5 g lactose given as a placebo | Bifidobacteria adolescentis BD1, 10^9 | Bifidobacteria animalis subsp. lactis BB-12, 10^9 | galacto-oligosaccharide (5 g) and Bifidobacteria adolescentis BD1 (10^9) | galacto-oligosaccharide (5 g) and Bifidobacteria animalis subsp. lactis BB-12 (10^9) | galactooligosaccaride, 5 g | Total of all reporting groups |
| Overall Participants | 17 | 14 | 14 | 16 | 17 | 16 | 94 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
43.9
(8.8)
|
44.7
(13.3)
|
43.9
(12.5)
|
44.2
(11.8)
|
43.1
(12.7)
|
45.9
(9.6)
|
44.3
(11.2)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
13
76.5%
|
9
64.3%
|
12
85.7%
|
11
68.8%
|
12
70.6%
|
12
75%
|
69
73.4%
|
| Male |
4
23.5%
|
5
35.7%
|
2
14.3%
|
5
31.3%
|
5
29.4%
|
4
25%
|
25
26.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||
| Hispanic or Latino |
0
0%
|
2
14.3%
|
2
14.3%
|
2
12.5%
|
2
11.8%
|
1
6.3%
|
9
9.6%
|
| Not Hispanic or Latino |
17
100%
|
12
85.7%
|
12
85.7%
|
14
87.5%
|
15
88.2%
|
15
93.8%
|
85
90.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||
| White |
5
29.4%
|
8
57.1%
|
4
28.6%
|
3
18.8%
|
6
35.3%
|
5
31.3%
|
31
33%
|
| African American |
10
58.8%
|
6
42.9%
|
7
50%
|
13
81.3%
|
11
64.7%
|
11
68.8%
|
58
61.7%
|
| Other |
2
11.8%
|
0
0%
|
3
21.4%
|
0
0%
|
0
0%
|
0
0%
|
5
5.3%
|
| Region of Enrollment (participants) [Number] | |||||||
| United States |
17
100%
|
14
100%
|
14
100%
|
16
100%
|
17
100%
|
16
100%
|
94
100%
|
| Education (Count of Participants) | |||||||
| Less than or equal to 12 years |
3
17.6%
|
1
7.1%
|
2
14.3%
|
6
37.5%
|
2
11.8%
|
6
37.5%
|
20
21.3%
|
| Greater than 12 years |
14
82.4%
|
13
92.9%
|
12
85.7%
|
10
62.5%
|
15
88.2%
|
10
62.5%
|
74
78.7%
|
Outcome Measures
| Title | Change in Microbiota, as Measured by Change in Microbiota Composition, Including Presence of B. Adolescentis BD1 and B. Animalis Supsp Lactis BB-12 |
|---|---|
| Description | change in microbiota composition, including presence of B. adolescentis BD1 and B. animalis supsp lactis BB-12 |
| Time Frame | baseline and three weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Mann-Whitney-Wilcoxon matched pair tests |
| Arm/Group Title | Placebo | Probiotic 1 | Probiotic 2 | Synbiotic 1 | Synbiotic 2 | Prebiotic |
|---|---|---|---|---|---|---|
| Arm/Group Description | 5 g lactose given as a placebo | Bifidobacteria adolescentis BD1, 10^9 | Bifidobacteria animalis subsp. lactis BB-12, 10^9 | galacto-oligosaccharide (5 g) and Bifidobacteria adolescentis BD1 (10^9) | galacto-oligosaccharide (5 g) and Bifidobacteria animalis subsp. lactis BB-12 (10^9) | galactooligosaccharide, 5 g |
| Measure Participants | 17 | 14 | 14 | 16 | 17 | 16 |
| Bifidobacterium Baseline |
7.9
(8.1)
|
9.1
(5.3)
|
8.8
(5.7)
|
6.0
(5.9)
|
8.7
(6.2)
|
11.3
(10.5)
|
| Bifidobacterium Treatment End |
12.0
(8.0)
|
14.6
(6.9)
|
9.5
(8.4)
|
14.7
(7.4)
|
15.9
(8.0)
|
17.4
(11.4)
|
| OTU_1 (B adolescentis) Baseline |
1.2
(1.9)
|
1.2
(4.2)
|
1.2
(2.5)
|
2.5
(4.5)
|
3.1
(4.5)
|
3.8
(7.5)
|
| OTU_1 (B adolescentis) Treatment End |
2.6
(4.1)
|
3.4
(5.1)
|
1.1
(1.6)
|
7.3
(7.0)
|
6.8
(9.6)
|
6.6
(8.8)
|
| OTU_167 (B. animalis subsp. lactis) Baseline |
0.0
(0.0)
|
0.0
(0.0)
|
0.0
(0.0)
|
0.0
(0.0)
|
0.0
(0.0)
|
0.0
(0.0)
|
| OTU_167 (B. animalis subsp. lactis) Treatment End |
0.0
(0.1)
|
0.0
(0.0)
|
0.1
(0.1)
|
0.0
(0.0)
|
0.1
(0.2)
|
0.2
(0.9)
|
| Title | Change in Intestinal Permeability as Measured by Change in Percent Sugars in Urine |
|---|---|
| Description | Change in intestinal permeability as measured by change in percent sugars in urine |
| Time Frame | baseline and three weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Probiotic 1 | Probiotic 2 | Synbiotic 1 | Synbiotic 2 | Prebiotic |
|---|---|---|---|---|---|---|
| Arm/Group Description | 5 g lactose given as a placebo | Bifidobacteria adolescentis BD1, 10^9 | Bifidobacteria animalis subsp. lactis BB-12, 10^9 | galacto-oligosaccharide (5 g) and Bifidobacteria adolescentis BD1 (10^9) | galacto-oligosaccharide (5 g) and Bifidobacteria animalis subsp. lactis BB-12 (10^9) | galactooligosaccharide, 5 g |
| Measure Participants | 17 | 14 | 14 | 16 | 17 | 16 |
| Sucralose:Lactulose with aspirin Baseline |
0.32
(0.20)
|
0.34
(0.21)
|
0.34
(0.30)
|
0.32
(0.23)
|
0.36
(0.19)
|
0.37
(0.19)
|
| Sucralose:Lactulose with aspirin Treatment End |
0.36
(0.25)
|
0.20
(0.16)
|
0.26
(0.18)
|
0.20
(0.16)
|
0.29
(0.16)
|
0.23
(0.15)
|
| Title | Endotoxemia, as Measured by Change in Circulating Endotoxin by Lipopolysaccharide and Lipopolysaccharide-binding Protein |
|---|---|
| Description | Endotoxemia, as measured by change in circulating endotoxin by lipopolysaccharide and lipopolysaccharide-binding protein |
| Time Frame | baseline and three weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Probiotic 1 | Probiotic 2 | Synbiotic 1 | Synbiotic 2 | Prebiotic |
|---|---|---|---|---|---|---|
| Arm/Group Description | 5 g lactose given as a placebo | Bifidobacteria adolescentis BD1, 10^9 | Bifidobacteria animalis subsp. lactis BB-12, 10^9 | galacto-oligosaccharide (5 g) and Bifidobacteria adolescentis BD1 (10^9) | galacto-oligosaccharide (5 g) and Bifidobacteria animalis subsp. lactis BB-12 (10^9) | galactooligosaccharide, 5 g |
| Measure Participants | 16 | 14 | 14 | 14 | 17 | 15 |
| Lipopolysaccharide Baseline |
0.02
(0.02)
|
0.03
(0.03)
|
0.3
(0.03)
|
0.02
(0.03)
|
0.02
(0.02)
|
0.02
(0.02)
|
| Lipopolysaccharide Treatment End |
0.02
(0.04)
|
0.03
(.03)
|
0.03
(0.06)
|
0.02
(0.04)
|
0.02
(0.02)
|
0.02
(0.01)
|
Adverse Events
| Time Frame | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | Placebo | Probiotic 1 | Probiotic 2 | Synbiotic 1 | Synbiotic 2 | Prebiotic | ||||||
| Arm/Group Description | 5 g lactose given as a placebo | Bifidobacteria adolescentis BD1, 10^9 | Bifidobacteria animalis subsp. lactis BB-12, 10^9 | galacto-oligosaccharide (5 g) and Bifidobacteria adolescentis BD1 (10^9) | galacto-oligosaccharide (5 g) and Bifidobacteria animalis subsp. lactis BB-12 (10^9) | galactooligosaccaride, 5 g | ||||||
All Cause Mortality |
||||||||||||
| Placebo | Probiotic 1 | Probiotic 2 | Synbiotic 1 | Synbiotic 2 | Prebiotic | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/14 (0%) | 0/14 (0%) | 0/16 (0%) | 0/17 (0%) | 0/16 (0%) | ||||||
Serious Adverse Events |
||||||||||||
| Placebo | Probiotic 1 | Probiotic 2 | Synbiotic 1 | Synbiotic 2 | Prebiotic | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/14 (0%) | 0/14 (0%) | 0/16 (0%) | 0/17 (0%) | 0/16 (0%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| Placebo | Probiotic 1 | Probiotic 2 | Synbiotic 1 | Synbiotic 2 | Prebiotic | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/14 (0%) | 0/14 (0%) | 0/16 (0%) | 0/17 (0%) | 0/16 (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.
Results Point of Contact
| Name/Title | Heather Rasmussen, Assistant Professor |
|---|---|
| Organization | University of Nebraska-Lincoln |
| Phone | 402-472-1373 |
| hrasmussen2@unl.edu |
Responsible Party:
Rush University Medical Center
ClinicalTrials.gov Identifier:
NCT02355210
Other Study ID Numbers:
- USDA-NIFA-AFRI-003397
First Posted:
Feb 4, 2015
Last Update Posted:
Nov 23, 2021
Last Verified:
Nov 1, 2021