Trial Outcomes & Findings for Blood Lipopolysaccharide (LPS) Rifaximin Study (NCT NCT02124512)

Last Updated: 2019-08-21

Results Overview

Plasma lipopolysaccharide (LPS) will be measured both in the fasting state and after a lipid-rich meal in obese subjects (Pre-Treatment: 0, 4 and 8 hr timepoints). The subjects will then be treated with the antibiotic rifaximin for 12 weeks to substantially reduce gut bacteria. LPS measurements at fasting and after a lipid-rich meal will be repeated (Post-Treatment: 0, 4 and 8 hr timepoints). The lipid tolerance tests before and after treatment with rifaximin will be assessed to determine whether there is a reduction in post-prandial LPS. LPS measurements were obtained using a modified LAL Assay.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

0, 4 and 8 hours at Baseline, and 0, 4 and 8 hours after 12 weeks of treatment

Results posted on

2019-08-21

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1 Rifaximin SSD Subjects randomized to this arm of the study will receive 80 mg per day Rifaximin SSD Rifaximin SSD: Study Drug dosing will be 80 mg SSD once daily	Arm 2 Placebo Placebo Placebo: 80 mg placebo once daily
Overall Study STARTED	6	6
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Blood Lipopolysaccharide (LPS) Rifaximin Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 Rifaximin SSD n=6 Participants Subjects randomized to this arm of the study will receive 80 mg per day Rifaximin SSD Rifaximin SSD: Study Drug dosing will be 80 mg SSD once daily	Arm 2 Placebo n=6 Participants Placebo Placebo: 80 mg placebo once daily	Total n=12 Participants Total of all reporting groups
Age, Continuous	50 years STANDARD_DEVIATION 3.0 • n=5 Participants	50 years STANDARD_DEVIATION 2.9 • n=7 Participants	50 years STANDARD_DEVIATION 3.0 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Body Mass Index (BMI)	38.5 kg/m^2 STANDARD_DEVIATION 4.2 • n=5 Participants	36.1 kg/m^2 STANDARD_DEVIATION 3.4 • n=7 Participants	37.3 kg/m^2 STANDARD_DEVIATION 3.8 • n=5 Participants

PRIMARY outcome

Timeframe: 0, 4 and 8 hours at Baseline, and 0, 4 and 8 hours after 12 weeks of treatment

Outcome measures

Outcome measures
Measure	Arm 1 Rifaximin SSD n=6 Participants Subjects randomized to this arm of the study will receive 80 mg per day Rifaximin SSD Rifaximin SSD: Study Drug dosing will be 80 mg SSD once daily	Arm 2 Placebo n=6 Participants Placebo Placebo: 80 mg placebo once daily
Circulating LPS Post-treatment 4hr	8.45 EU/mL Standard Error 1.87	9.97 EU/mL Standard Error 4.30
Circulating LPS Pre-treatment 0hr	2.44 EU/mL Standard Error 0.40	1.86 EU/mL Standard Error 0.33
Circulating LPS Pre-treatment 4hr	13.66 EU/mL Standard Error 2.93	10.00 EU/mL Standard Error 1.55
Circulating LPS Pre-treatment 8hr	1.71 EU/mL Standard Error 0.26	1.04 EU/mL Standard Error 0.48
Circulating LPS Post-treatment 0hr	1.89 EU/mL Standard Error 0.35	1.86 EU/mL Standard Error 0.43
Circulating LPS Post-treatment 8hr	2.14 EU/mL Standard Error 0.49	2.29 EU/mL Standard Error 0.81

SECONDARY outcome

Timeframe: Pre-Treatment (baseline) and Post-Treatment (12 weeks after baseline).

Subjects will undergo a baseline fat biopsy (pre-treatment). They will then be treated with rifaximin for 12 weeks and biopsies will be repeated to determine if disruption of the microbiota reduces tissue inflammation. Data are reported as normalized mRNA expression levels (arbitrary units) of TNFalpha.

Outcome measures

Outcome measures
Measure	Arm 1 Rifaximin SSD n=6 Participants Subjects randomized to this arm of the study will receive 80 mg per day Rifaximin SSD Rifaximin SSD: Study Drug dosing will be 80 mg SSD once daily	Arm 2 Placebo n=6 Participants Placebo Placebo: 80 mg placebo once daily
Tissue Inflammation Pre-Treatment	2.00 arbitrary units Standard Error 0.25	1.30 arbitrary units Standard Error 0.13
Tissue Inflammation Post-Treatment	1.67 arbitrary units Standard Error 0.25	1.46 arbitrary units Standard Error 0.28

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 weeks

We hypothesize that a change in the microbial flora with rifaximin will alter plasma LPS, adipose tissue inflammation, and insulin sensitivity. Therefore, we will examine, before and after rifaximin/placebo treatment: 1. LPS associated with lipoproteins, 2. insulin sensitivity and hepatic glucose production, 3. plasma inflammatory markers (TNFα, IL-6, MCP-1, adiponectin), 4. adipose inflammatory markers (CD68, MCP1, TNFα, PAI1, IL12, IL10, TLR4 and others).

Outcome measures

Outcome data not reported

Adverse Events

Arm 1 Rifaximin SSD

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm 2 Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Philip Kern

University of Kentucky

Phone: 859-323-2232

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place