- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03860584
Alleviation Of Metabolic Endotoxemia In Adults With Metabolic Syndrome With Milk Fat Globule Membrane
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background and hypothesis:
Our preclinical evidence shows that phospholipid-rich milk fat globule membrane (MFGM) attenuates lipopolysaccharide-induced increases in gut permeability and pro-inflammatory cytokines. MFGM also attenuates inflammation in association with a prebiotic and/or antimicrobial activity that modulates microbiota composition. Our central hypothesis is that MFGM-enriched dairy milk compared with a matched milk beverage containing soy lecithin (control) decreases metabolic endotoxemia and improves glucose tolerance in metabolic syndrome (MetS) adults by increasing gut barrier integrity in association with alleviating gut dysbiosis and inflammation.
Study Design:
The investigators will enroll male and female MetS adults (n = 24; 18-65 y) to complete a 2-arm, double-blind, randomized controlled, crossover trial. They will be randomized in 4-unit blocks to receive, for 14 days, a controlled diet with dairy milk (3.5% fat; 3 servings/d) enriched with MFGM-derived phospholipid or a matched dairy milk that instead contains coconut and palm oil (control). The investigators will provide all foods during each study period to ensure weight maintenance and to increase homogeneity of gut and host responses.
Subjects:
Participants will be recruited from Columbus, OH area. Participants having no history of liver or cardiovascular disease or cancer will be enrolled. They will have ≥3 established criteria for MetS: i) glucose (100-126 mg/dL), ii) waist circumference (>89 or >102 cm for F/M), iii) HDL-C (<50 or <40 mg/dL in F/M), iv) TG >150 mg/dL, and iv) blood pressure >130/85 mmHg. Major exclusion criteria include: unstable body mass (±2 kg over prior 3-mo) vegetarian; food allergies or lactose intolerance; user of dietary supplements or probiotics (within past 1-mo); pregnancy, lactation, changes in birth control (within 6-month); any gastrointestinal disorders; chronic diarrhea; smoker; excess alcohol (>2 drinks/day); excess aerobic exercise (>7 h/week); recent antibiotic or anti-inflammatory agent use; blood pressure >140/90 mmHg.
Dietary Control:
The intervention will be performed in the Human Nutrition Metabolic Kitchen under the auspice of a registered dietitian (PI Bruno). In each 2-wk intervention, participants' diet will be rigorously controlled. All foods will be prepared, packaged, and provided every 3-4 days to supply a weight maintenance (i.e. eucaloric) diet. To assess compliance, participants will return MFGM/coconut/palm oil milk bottles for counting and any uneaten food portions for weighed measurement. Milk beverages will also be formulated to contain para-aminobenzoic acid (PABA; 80 mg/milk serving). Spot urine samples will be collected 4 times during each study arm coinciding when participants pick up test foods. Urinary PABA will be measured by spectrophotometry. Separate from this, participants will also keep food logs to document any dietary deviation. Diets will be standardized at 50-60% of energy from carbohydrate with low fiber intakes (~15 g/day) similar to Americans' diets to prevent potential masking of the benefits of MFGM, 15-20% from protein, and 25-30% from fat. Importantly, other than test beverages provided as part of the eucaloric diet, diets will be otherwise devoid of significant amounts of dairy foods, fermented products, and probiotics to prevent confounding effects.
Measurements:
Anthropometrics and blood pressure will be assessed at days 0, 7, and 14. Prior to (day 0), at day 7 and after each 2-wk arm (day 14), a fasting blood sample will be collected to assess serum endotoxin and metabolic chemistries (glucose, insulin, lipids (triglyceride, total and HDL cholesterol), and TLR4/NFκB-dependent genes from whole blood. A breath sample will be collected to assess the correlation analysis of plasma metabolic biomarkers. After the 2-week intervention, from fecal samples collected on day 13, the investigators will assess microbiota composition and function, SCFAs, and intestinal inflammatory markers (calprotectin, myeloperoxidase). During this period, participants will also record daily stool characteristics using a 7-point Bristol Stool scale. On days 14, participants in the fasted state will receive a high-fat/high-glucose meal challenge to induce gut-derived endotoxin translocation. At 30-minute intervals for 3 hours, the investigators will evaluate circulating endotoxin, glucose, and insulin; TLR4/NFκB-dependent genes will be assessed from whole blood at 0 hour and 3-hour. Gut permeability probes will be co-administered with the test meal challenge, and 24-hour urine will be collected to assess gut barrier integrity. Participants will then undergo a 2-week washout prior to receiving the alternative treatment and completing all procedures in an identical manner.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Ohio
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Columbus, Ohio, United States, 43201
- The Ohio State University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Serum Glucose 100-126 mg/dl
- Waist C >89/102 cm; F/M
- Serum HDL-C: <50/40 mg/dl; F/M
- Serum TG: >150 mg/dl
- BP >130/85 mmHg
- Serum Endotoxin >25 EU/ml
Exclusion Criteria:
- Unstable body mass (±2 kg over prior 3-mo)
- Vegetarian
- Food allergies or lactose intolerance
- User of dietary supplements or probiotics (within past 1-mo)
- Pregnancy, lactation, changes in birth control (within 6-mo)
- Any gastrointestinal disorders
- Chronic diarrhea
- Smoker
- Excess alcohol (>2 drinks/d)
- Excess aerobic exercise (>5 h/wk)
- Recent antibiotic or anti-inflammatory agent use
- BP >140/90 mmHg
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MFGM-enriched full-fat dairy milk
Participants in this arm will receive MFGM-enriched full-fat dairy milk (3 servings/d) that contains MFGM at 10% phospholipid (relative to total lipid content) delivering MFGM at ~10-times that in full-fat dairy milk.
|
MetS adults with metabolic endotoxemia will be enrolled to complete a 2-arm, double-blind, randomized controlled, crossover trial to test the independent benefits of MFGM.
For each 2-wk arm, they will receive MFGM-enriched full-fat dairy milk (3 servings/d) or a matched dairy milk that instead contains soy phospholipid/lecithin (control).
Milks have been formulated with soy lecithin or MFGM at 10% phospholipid (relative to total lipid content).
This delivers MFGM at ~10-times that in full-fat dairy milk, which reflects that consumers obtain MFGM from dairy foods other than whole milk.
|
Placebo Comparator: Soy phospholipid/lecithin milk
Participants in this arm will receive a matched dairy milk that instead contains soy phospholipid/lecithin.
|
MetS adults with metabolic endotoxemia will be enrolled to complete a 2-arm, double-blind, randomized controlled, crossover trial to test the independent benefits of MFGM.
For each 2-wk arm, they will receive MFGM-enriched full-fat dairy milk (3 servings/d) or a matched dairy milk that instead contains soy phospholipid/lecithin (control).
Milks have been formulated with soy lecithin or MFGM at 10% phospholipid (relative to total lipid content).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum Endotoxin (LPS)
Time Frame: day 14
|
Between-treatment change in serum endotoxin (fasting) on day 14 relative to day 0
|
day 14
|
Serum Endotoxin (LPS)
Time Frame: day 14 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)
|
Between-treatment difference in the area under the curve of serum endotoxin (0-3 hours) on day 14
|
day 14 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)
|
Plasma Glucose
Time Frame: day 14
|
Between-treatment change in plasma glucose (fasting) on day 14 relative to day 0
|
day 14
|
Plasma Glucose
Time Frame: day 14 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)
|
Between-treatment difference in the area under the curve of plasma glucose (0-3 hours) on day 14
|
day 14 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma Insulin
Time Frame: day 14
|
Between-treatment change in plasma (fasting) on day 14 relative to day 0
|
day 14
|
Plasma Insulin
Time Frame: day 14 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)
|
Between-treatment difference in the area under the curve of plasma insulin (0-3 hours) on day 14
|
day 14 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)
|
Plasma HDL-C
Time Frame: day 14
|
Between-treatment change in plasma HDL-C (fasting) on day 14 relative to day 0
|
day 14
|
Plasma Triglyceride
Time Frame: day 14
|
Between-treatment change in plasma triglyceride (fasting) on day 14 relative to day 0
|
day 14
|
Plasma Total Cholesterol
Time Frame: day 14
|
Between-treatment change in plasma total cholesterol (fasting) on day 14 relative to day 0
|
day 14
|
Plasma glucagon-like peptide-1
Time Frame: day 14
|
Between-treatment change in plasma glucagon-like peptide-1 (fasting) on day 14 relative to day 0
|
day 14
|
Urine Lactulose
Time Frame: day 14
|
Between-treatment difference in 24 hour urinal excretion of lactulose post-meal challenge on day 14
|
day 14
|
Urine sucralose
Time Frame: day 14
|
Between-treatment difference in 24 hour urinal excretion of sucralose post-meal challenge on day 14
|
day 14
|
Urine erythritol
Time Frame: day 14
|
Between-treatment difference in 24 hour urinal excretion of erythritol post-meal challenge on day 14
|
day 14
|
Urine mannitol
Time Frame: day 14
|
Between-treatment difference in 24 hour urinal excretion of mannitol post-meal challenge on day 14
|
day 14
|
Fecal bacterial abundance and composition
Time Frame: day 13
|
Between-treatment difference in fecal bacterial abundance and composition on day 13
|
day 13
|
Fecal Acetate
Time Frame: day 13
|
Between-treatment difference in fecal acetate on day 13
|
day 13
|
Fecal Butyrate
Time Frame: day 13
|
Between-treatment difference in fecal butyrate on day 13
|
day 13
|
Fecal Propionate
Time Frame: day 13
|
Between-treatment difference in fecal propionate on day 13
|
day 13
|
Plasma gastric inhibitory polypeptide (GIP)
Time Frame: day 14
|
Between-treatment change in plasma gastric inhibitory polypeptide (GIP) (fasting) on day 14 relative to day 0
|
day 14
|
Fecal Calprotectin
Time Frame: day 13
|
Between-treatment difference in fecal calprotectin on day 13
|
day 13
|
Fecal Myeloperoxidase
Time Frame: day 13
|
Between-treatment difference in fecal myeloperoxidase on day 13
|
day 13
|
Circulating Toll-like receptor 4 mRNA
Time Frame: day 14
|
Between-treatment change in circulating Toll-like receptor 4 mRNA (fasting) on day 14 relative to day 0
|
day 14
|
Circulating IL-6 mRNA
Time Frame: day 14
|
Between-treatment change in circulating IL-6 mRNA (fasting) on day 14 relative to day 0
|
day 14
|
Circulating TNFa mRNA
Time Frame: day 14
|
Between-treatment change in circulating TNFa mRNA (fasting) on day 14 relative to day 0
|
day 14
|
Circulating Toll-like receptor 4 mRNA
Time Frame: day 14 (0, 3 hour post-meal challenge)
|
Between-treatment change in circulating Toll-like receptor 4 mRNA post meal challenge (0-3 h) on day 14
|
day 14 (0, 3 hour post-meal challenge)
|
Circulating IL-6 mRNA
Time Frame: day 14 (0, 3 hour post-meal challenge)
|
Between-treatment change in circulating IL-6 mRNA post meal challenge (0-3 h) on day 14
|
day 14 (0, 3 hour post-meal challenge)
|
Circulating TNFa mRNA
Time Frame: day 14 (0, 3 hour post-meal challenge)
|
Between-treatment change in circulating TNFa mRNA post meal challenge (0-3 h) on day 14
|
day 14 (0, 3 hour post-meal challenge)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Richard Bruno, PhD, Ohio State University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2018H0564
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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