Blood Lipopolysaccharide (LPS) Rifaximin Study

NCT02124512 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 14-0136-F1VUL1TR0001171R21DK100258-01A1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic syndrome is a condition involving elevated levels of fat in the blood, a tendency towards diabetes, hypertension, and too much fat around the abdomen (an increased waistline). Individuals with metabolic syndrome often have impaired glucose tolerance, which is a condition where blood sugar is normal when fasting (before eating), but is too high after drinking a sugary drink. This is due to an abnormality in the body's sensitivity to insulin (insulin resistance), which is due in part to an inability of the muscle to take up glucose. People with metabolic syndrome have inflammation in their fat tissue and in their blood stream, and the changes in the level of inflammatory chemicals produced by cells in your fat tissues will be studied. One possible source of the inflammation may be the bacteria in the intestine. When individuals eat fatty foods, some of the bacterial products become attached to the fat in their blood and then get directed to fat tissue. The investigators wish to determine whether individuals have an excessive amount of inflammation in their fat tissues, and whether this inflammation comes from the bacteria in their intestines. To determine this, the investigators wish to treat individuals with an antibiotic that reduces the bacteria in their intestines and in their blood, and determine whether this reduces their overall level of inflammation.

Conditions

Obese; Insulin Resistance; Metabolic Syndrome

Keywords

obese; insulin resistance; metabolic syndrome

Outcome Measures

Primary Outcomes (1)

• Circulating LPS

  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.

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

Secondary Outcomes (1)

• Tissue Inflammation

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

Other Outcomes (1)

• Improved Insulin Sensitivity

  Up to 12 weeks

Study Arms (2)

Arm 1 Rifaximin SSD

EXPERIMENTAL

Subjects randomized to this arm of the study will receive 80 mg per day Rifaximin SSD

Drug: Rifaximin SSD

Arm 2 Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Rifaximin SSD DRUG

Study Drug dosing will be 80 mg SSD once daily

Arm 1 Rifaximin SSD

Placebo OTHER

80 mg placebo once daily

Arm 2 Placebo

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Obese
• Insulin resistance or metabolic syndrome
• Body Mass Index between 27 and 45
• Waist circumference \>40" (M) or \>35" (F)
• Impaired glucose tolerance (IGT)
• Normal glucose tolerance (NGT) with at least three features of MetS
• A1C \<6.5
• Blood pressure 130/85

You may not qualify if:

• Pregnant or breastfeeding
• Recent or unstable cardiovascular disease
• cancer,
• Renal insufficiency (GFR\<30)
• Steroid use
• chronic inflammatory conditions
• Anticoagulant use
• Lipodystrophy
• Irritable Bowel Syndrome
• Allergy to local anesthetic
• Lactose intolerance

Sponsors & Collaborators

• Philip Kern: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Kentucky Center for Clinical and Translational Science

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Conditions

Obesity; Insulin Resistance; Metabolic Syndrome

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Results Point of Contact

• Title: Philip Kern
• Organization: University of Kentucky

pake222@uky.edu

859-323-2232

Study Officials

• Phililp Kern, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 23, 2014
• First Posted: April 28, 2014
• Study Start: March 1, 2015
• Primary Completion: May 31, 2019
• Study Completion: May 31, 2019
• Last Updated: August 21, 2019
• Results First Posted: August 21, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)