Trial Outcomes & Findings for Effects of the Probiotic Visbiome Extra Strength on Gut Microbiome & Immune Activation Markers (NCT NCT02706717)

NCT ID: NCT02706717

Last Updated: 2020-01-06

Results Overview

Baseline is defined as the average of the Entry and Week 2 values. Week 25/26 is defined as the average of the Week 25 and Week 26 values. Absolute change was calculated as the value at Week 25/26 minus the value at Baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 93 participants
• Primary outcome timeframe: Weeks 0, 2, 25, and 26
• Results posted on: 2020-01-06

Participant Flow

Enrollment began in 04/2016 and completed in 12/2016.

Participant milestones

Measure	Visbiome Extra Strength Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Overall Study STARTED	47	46
Overall Study COMPLETED	46	35
Overall Study NOT COMPLETED	1	11

Reasons for withdrawal

Measure	Visbiome Extra Strength Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Overall Study Withdrawal by Subject	1	8
Overall Study Lost to Follow-up	0	1
Overall Study Physician Decision	0	1
Overall Study Death	0	1

Baseline Characteristics

One participant in the placebo arm did not have height collected on study and is thus missing BMI.

Baseline characteristics by cohort

Measure	Visbiome Extra Strength n=47 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=46 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Total n=93 Participants Total of all reporting groups
Age, Continuous	51 years n=47 Participants	51.5 years n=46 Participants	51 years n=93 Participants
Sex: Female, Male Female	7 Participants n=47 Participants	6 Participants n=46 Participants	13 Participants n=93 Participants
Sex: Female, Male Male	40 Participants n=47 Participants	40 Participants n=46 Participants	80 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=47 Participants	9 Participants n=46 Participants	19 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=47 Participants	37 Participants n=46 Participants	74 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=47 Participants	0 Participants n=46 Participants	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=47 Participants	2 Participants n=46 Participants	2 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=47 Participants	1 Participants n=46 Participants	1 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=47 Participants	0 Participants n=46 Participants	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	21 Participants n=47 Participants	17 Participants n=46 Participants	38 Participants n=93 Participants
Race (NIH/OMB) White	24 Participants n=47 Participants	26 Participants n=46 Participants	50 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=47 Participants	0 Participants n=46 Participants	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=47 Participants	0 Participants n=46 Participants	2 Participants n=93 Participants
Region of Enrollment Puerto Rico	1 Participants n=47 Participants	0 Participants n=46 Participants	1 Participants n=93 Participants
Region of Enrollment United States	46 Participants n=47 Participants	46 Participants n=46 Participants	92 Participants n=93 Participants
Smoking Status Never	15 Participants n=47 Participants	19 Participants n=46 Participants	34 Participants n=93 Participants
Smoking Status Former	23 Participants n=47 Participants	15 Participants n=46 Participants	38 Participants n=93 Participants
Smoking Status Current	9 Participants n=47 Participants	10 Participants n=46 Participants	19 Participants n=93 Participants
Smoking Status Unknown or Not Reported	0 Participants n=47 Participants	2 Participants n=46 Participants	2 Participants n=93 Participants
Alcohol Status Never	3 Participants n=47 Participants	5 Participants n=46 Participants	8 Participants n=93 Participants
Alcohol Status Former	15 Participants n=47 Participants	8 Participants n=46 Participants	23 Participants n=93 Participants
Alcohol Status Current	29 Participants n=47 Participants	31 Participants n=46 Participants	60 Participants n=93 Participants
Alcohol Status Unknown or Not Reported	0 Participants n=47 Participants	2 Participants n=46 Participants	2 Participants n=93 Participants
Weight	87 kg n=47 Participants	81.3 kg n=46 Participants	83.1 kg n=93 Participants
BMI	27.3 kg/m^2 n=47 Participants • One participant in the placebo arm did not have height collected on study and is thus missing BMI.	26.2 kg/m^2 n=45 Participants • One participant in the placebo arm did not have height collected on study and is thus missing BMI.	27.1 kg/m^2 n=92 Participants • One participant in the placebo arm did not have height collected on study and is thus missing BMI.
CD4 Count	702 cells/mm^3 n=47 Participants	714.5 cells/mm^3 n=46 Participants	712 cells/mm^3 n=93 Participants
HIV-1 RNA <40 copies/mL	47 Participants n=47 Participants	45 Participants n=46 Participants	92 Participants n=93 Participants
HIV-1 RNA >=40 copies/mL	0 Participants n=47 Participants	1 Participants n=46 Participants	1 Participants n=93 Participants
sCD14	2249 ug/L n=47 Participants	2262 ug/L n=46 Participants	2255 ug/L n=93 Participants

PRIMARY outcome

Timeframe: Weeks 0, 2, 25, and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded.

Baseline is defined as the average of the Entry and Week 2 values. Week 25/26 is defined as the average of the Week 25 and Week 26 values.

Absolute change was calculated as the value at Week 25/26 minus the value at Baseline.

Outcome measures

Measure	Visbiome Extra Strength n=42 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=31 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in sCD14 From Baseline to Week 25/26	41 ug/L Interval -94.1 to 176.2	92.3 ug/L Interval -48.5 to 233.2

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

IL-6 data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 IP-10 data were excluded.

All values were log10 transformed prior to calculating change and conducting analyses.

Absolute change was calculated as the value at Week 26 minus the value at Week 2. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change.

Outcome measures

Measure	Visbiome Extra Strength n=42 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=30 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in IP-10 From Week 2 to Week 26	1.05 Fold change Interval 0.8 to 1.38	0.94 Fold change Interval 0.75 to 1.18

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

sCD163 data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

sTNF-RI data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

Oxidized LDL data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded.

Fold change was calculated as the value at Week 26 divided by the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=42 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=31 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in Kynurenine to Tryptophan Ratio From Week 2 to Week 26	1.039 ratio Interval 0.935 to 1.143	0.997 ratio Interval 0.944 to 1.05

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 D-dimer data were excluded.

All values were log10 transformed prior to calculating change and conducting analyses.

Absolute change was calculated as the value at Week 26 minus the value at Week 2. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change.

Outcome measures

Measure	Visbiome Extra Strength n=40 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=31 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in D-dimer From Week 2 to Week 26	1.203 Fold change Interval 0.967 to 1.496	0.937 Fold change Interval 0.787 to 1.115

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

LPS data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

LBP data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=42 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=31 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in CD4+ Cell Count From Week 2 to Week 26.	9.8 cells/mm^3 Interval -31.7 to 51.2	42.4 cells/mm^3 Interval -2.7 to 87.6

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded.

Fold change was calculated as the value at Week 26 divided by the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=42 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=31 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in CD4+/CD8+ Ratio From Week 2 to Week 26.	1.03 ratio Interval 0.99 to 1.07	1.05 ratio Interval 1.01 to 1.09

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD14++CD16- data were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=41 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=28 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in %CD14++CD16- From Week 2 to Week 26.	2.18 Percent of %CD14++CD16- cells Interval -1.16 to 5.53	-1.25 Percent of %CD14++CD16- cells Interval -3.31 to 0.8

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD14++CD16+ data were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=41 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=28 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in %CD14++CD16+ From Week 2 to Week 26	0.81 Percent of %CD14++CD16+ cells Interval -0.02 to 1.64	0.47 Percent of %CD14++CD16+ cells Interval -0.19 to 1.12

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

%CD14lowCD16hi data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

%CD4+CD38+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

%CD4+HLA-DR+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD4+CD38+HLA-DR+ data were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=41 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=28 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in %CD4+CD38+HLA-DR+ From Week 2 to Week 26.	-0.06 Percent of %CD4+CD38+HLA-DR+ cells Interval -0.25 to 0.29	-0.07 Percent of %CD4+CD38+HLA-DR+ cells Interval -0.28 to 0.14

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

%CD8+CD38+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: These data were not assayed and the analysis was abandoned.

%CD8+HLA-DR+ data are not available as of June, 2018. These data are based on assays which are to be tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 3 months after the primary completion date. Please note that these secondary outcomes were not included in the primary analysis report. There are many outcomes in this study and the labs had to give priority to the assays planned to be included in the primary manuscript.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD8+CD38+HLA-DR+ data were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=41 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=28 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in %CD8+CD38+HLA-DR+ From Week 2 to Week 26.	0.19 Percent of %CD8+CD38+HLA-DR+ cells Interval -0.47 to 0.86	-0.13 Percent of %CD8+CD38+HLA-DR+ cells Interval -0.78 to 0.53

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD4+CD28-CD57+ data were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=41 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=28 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in %CD4+CD28-CD57+ From Week 2 to Week 26.	-0.08 Percent of %CD4+CD28-CD57+ cells Interval -0.57 to 0.4	-0.09 Percent of %CD4+CD28-CD57+ cells Interval -0.72 to 0.53

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 %CD8+CD28-CD57+ data were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=41 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=28 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in %CD8+CD28-CD57+ From Week 2 to Week 26.	0.77 Percent of %CD8+CD28-CD57+ cells Interval -0.59 to 2.13	-1.50 Percent of %CD8+CD28-CD57+ cells Interval -3.36 to 0.35

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 Chao1 richness index data were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Chao1 is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Chao reference). Chao1 diversity is a richness measure which quantifies how many different types there are in a given dataset. The Chao 1 index can range from 1 to infinity as it is constrained only by the number of types defined as measurable. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the "types" that are considered.

Outcome measures

Measure	Visbiome Extra Strength n=29 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=21 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in Chao1 Richness Index From Week 2 to Week 26.	48.8 Estimator of species richness Interval -151.0 to 249.0	78.2 Estimator of species richness Interval -205.0 to 362.0

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 Shannon diversity index data were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Shannon is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Lemos and Magurran references). The Shannon index is an estimator of richness and evenness. It quantifies uncertainty (entropy) within a dataset. The Shannon Index ranges from 0-5. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the "types" that are considered.

Outcome measures

Measure	Visbiome Extra Strength n=29 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=21 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in Shannon Diversity Index From Week 2 to Week 26.	0.11 Estimator of species richness & evenness Interval -0.09 to 0.32	0.13 Estimator of species richness & evenness Interval -0.21 to 0.47

SECONDARY outcome

Timeframe: Weeks 26 and 38

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 26 and Week 38 Chao1 richness index data were excluded.

Absolute change was calculated as the value at Week 38 minus the value at Week 26.

Chao1 is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Chao reference). Chao1 diversity is a richness measure which quantifies how many different types there are in a given dataset. The Chao 1 index can range from 1 to infinity as it is constrained only by the number of types defined as measurable. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the "types" that are considered.

Outcome measures

Measure	Visbiome Extra Strength n=29 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=22 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in Chao1 Richness Index From Week 26 to Week 38.	23 Estimator of species richness Interval -227.0 to 273.0	-14.1 Estimator of species richness Interval -385.0 to 357.0

SECONDARY outcome

Timeframe: Weeks 26 and 38

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 26 and Week 38 Shannon diversity index data were excluded.

Absolute change was calculated as the value at Week 38 minus the value at Week 26.

Shannon is a diversity index that reflects how many different quantifiable types (species, individuals, items, etc…) there are in a dataset (see Lemos and Magurran references). The Shannon index is an estimator of richness and evenness. It quantifies uncertainty (entropy) within a dataset. The Shannon Index ranges from 0-5. The greater a value is, the more diverse it is but only in direct comparison to groups considering the same parameters. That is, diversity indices are relative to the community (cohort or ecosystem) studied in part due to the definition of the "types" that are considered.

Outcome measures

Measure	Visbiome Extra Strength n=29 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=22 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in Shannon Diversity Index From Week 26 to Week 38.	-0.10 Estimator of species richness & evenness Interval -0.46 to 0.26	0.03 Estimator of species richness & evenness Interval -0.35 to 0.41

SECONDARY outcome

Timeframe: Weeks 2 and 26

Population: Analysis used the per-protocol population. Participants 1) without Baseline AND Week 25/26 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) or with HIV-1 virologic failure were excluded. Additionally, participants without Week 2 and Week 26 I-FABP data were excluded.

Absolute change was calculated as the value at Week 26 minus the value at Week 2.

Outcome measures

Measure	Visbiome Extra Strength n=42 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=30 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Change in I-FABP From Week 2 to Week 26.	0.59 ng/mL Interval 0.26 to 1.34	0.83 ng/mL Interval 0.37 to 1.86

SECONDARY outcome

Timeframe: Treatment dispensation to Week 38

Population: All enrolled participants who initiated study treatment.

Summary of the highest adverse event grade (0-5) for each participant.

Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade.

DAIDS AE Grading Table, Version 2.0 was used.

Outcome measures

Measure	Visbiome Extra Strength n=47 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=43 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Safety Grade 0	32 Participants	35 Participants
Safety Grade 1	3 Participants	3 Participants
Safety Grade 2	5 Participants	1 Participants
Safety Grade 3	5 Participants	3 Participants
Safety Grade 4	2 Participants	0 Participants
Safety Grade 5	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Treatment dispensation to Week 38

Population: All enrolled participants who initiated study treatment.

Tolerability was successfully completing the protocol-defined treatment period.

Outcome measures

Measure	Visbiome Extra Strength n=47 Participants Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=43 Participants Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Tolerability Completed as defined by protocol	43 Participants	31 Participants
Tolerability Did not complete as defined by protocol	4 Participants	12 Participants

Adverse Events

Visbiome Extra Strength

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo for Visbiome Extra Strength

Serious events: 2 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	Visbiome Extra Strength n=47 participants at risk Visibiome: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.	Placebo for Visbiome Extra Strength n=46 participants at risk Placebo: From week 2 to 4, participant will receive one sachet orally daily. From week 4 to 26, participant will receive one sachet orally twice daily.
Gastrointestinal disorders Abdominal pain	2.1% 1/47 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.	0.00% 0/46 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.
Infections and infestations Gastroenteritis	2.1% 1/47 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.	0.00% 0/46 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.
Infections and infestations Meningoencephalitis herpetic	0.00% 0/47 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.	2.2% 1/46 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.
Injury, poisoning and procedural complications Comminuted fracture	0.00% 0/47 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.	2.2% 1/46 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.
Injury, poisoning and procedural complications Overdose	2.1% 1/47 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.	0.00% 0/46 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/47 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.	2.2% 1/46 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.
Musculoskeletal and connective tissue disorders Back pain	2.1% 1/47 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.	0.00% 0/46 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.1% 1/47 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.	0.00% 0/46 • Week 0 to Week 38. Protocol definition of Adverse Events: 1) signs and symptoms Grade ≥3 and any that led to a change in treatment regardless of grade; 2) new diagnoses; 3) Grade ≥3 lab values and any that led to a change in treatment or were associated with a diagnosis were recorded, regardless of grade. DAIDS AE Grading Table, Version 2.0 was used.

Other adverse events

Adverse event data not reported

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

Phone: (301) 628-3313

Email: ACTGCT.Gov@s-3.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60