Blood Lipopolysaccharide (LPS) Rifaximin Study
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|ClinicalTrials.gov Identifier: NCT02124512|
Recruitment Status : Recruiting
First Posted : April 28, 2014
Last Update Posted : March 14, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Obese Insulin Resistance Metabolic Syndrome||Drug: Rifaximin SSD Other: Placebo||Phase 2|
This is a randomized, placebo controlled proof of concept study that will examine the investigational drug Rifaximin Soluble Solid Dispersion (SSD) ability to reduce gut microbiota and thereby reduce adipose inflammation and improve insulin resistance.
Each subject enrolled will undergo a fat tolerance test with a high fat meal, an oral glucose tolerance test, a fat biopsy, and a euglycemic clamp. Following their successful completion of those procedures subjects will be randomized to study treatment. That treatment will involve receiving the investigational drug,80 mg per day of rifaximin soluable solid dispersion (SDD), or placebo for 8 weeks. All procedures will be performed on the Clinical Services Core of the CCTS. The initial visit will involve informed consent, and routine labs (comprehensive metabolic panel, lipid panel, TSH, CBC with platelets). These routine labs are for safety purposes and to rule out exclusionary disorders. A stool sample will also be collected and frozen for possible future analysis of bacterial microflora.
Subjects will be asked to allow the principal investigator to bank blood and tissue samples collected during this study that are not used for other study related tests. No additional blood or tissue samples will be collected. If the subject agrees to the banking of their blood and tissue samples they will be stored in the Principal Investigator's laboratory at the University of Kentucky for an indefinite period of time or until they are used up. Stored samples will be used for future research testing to learn about how to prevent, detect, or treat insulin resistance, metabolic syndrome, diabetes or other health problems.
Each subject will undergo total body composition testing using a total body dual-energy x-ray absorptiometry (DXA) scan. The DXA scan measures the subject's bond density and body fat.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Dietary Fat, Lipoprotein and Lipopolysaccharide: Role in Insulin Resistance|
|Study Start Date :||March 2015|
|Estimated Primary Completion Date :||May 31, 2019|
|Estimated Study Completion Date :||June 2019|
Experimental: Arm 1 Rifaximin SSD
Subjects randomized to this arm of the study will receive 80 mg per day Rifaximin SSD
Drug: Rifaximin SSD
Study Drug dosing will be 80 mg SSD once daily
Placebo Comparator: Arm 2 Placebo
80 mg placebo once daily
- Decrease in circulating LPS [ Time Frame: up to 24 months ]We will measure plasma lipopolysaccharide (LPS) both in the fasting state and after a lipid-rich meal in obese MetS subjects. The subjects will then be treated with the antibiotic rifaximin for 8 weeks to substantially reduce gut bacteria. The lipid tolerance tests before and after treatment with rifaximin will be assessed to determine whether there is a reduction in post-prandial LPS.
- Decrease in tissue inflammation [ Time Frame: Up to 24 months ]Subjects will undergo a baseline fat biopsy and a euglycemic clamp to measure peripheral and hepatic insulin sensitivity. They will then be treated with rifaximin and the insulin sensitivity testing and biopsies will be repeated to determine if disruption of the microbiota reduces tissue inflammation and improves insulin sensitivity.
- Improved insulin sensitivity [ Time Frame: Up to 24 months ]We hypothesize that a change in the microbial flora with rifaximin will reduce plasma LPS, and this in turn will reduce adipose tissue inflammation, which may lead to improved 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02124512
|Contact: Dorothy Ross||(859) email@example.com|
|Contact: Philip Kern, MD||(859) firstname.lastname@example.org|
|United States, Kentucky|
|University of Kentucky Center for Clinical and Translational Science||Recruiting|
|Lexington, Kentucky, United States, 40536|
|Contact: Stacie BeBout 859-323-9987 email@example.com|
|Principal Investigator: Philip Kern, MD|
|Principal Investigator:||Phililp Kern, MD||University of Kentucky|