Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03860584 |
| Other study ID # |
2018H0564 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2019 |
| Est. completion date |
December 20, 2020 |
Study information
| Verified date |
June 2023 |
| Source |
Ohio State University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Metabolic syndrome (MetS) adults (n = 24; 18-65 y) will be enrolled to complete a 2-arm,
double-blind, randomized controlled, crossover trial. They will be randomized in 4-unit
blocks to receive, for 14 d, a controlled diet with dairy milk (3.5% fat; 3 servings/d)
enriched with milk fat globule membrane (MFGM, MEB) or a matched dairy milk that instead
contains soy lecithin/phospholipid (control, COMP). All foods during each study period will
be provided to ensure weight maintenance and to increase homogeneity of gut and host
responses. Anthropometrics and blood pressure will be assessed at days 0, 7, and 14. Prior to
(day 0) and after each 2-wk arm (day 14), a fasting blood sample will be collected to assess
serum endotoxin and metabolic chemistries (glucose, lipids, insulin), and Toll-like receptor
4 /nuclear factor kappaB (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, short chain fatty acids (SCFA), and intestinal
inflammatory markers (calprotectin, myeloperoxidase). On d 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-hour, 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.
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.
