Exercise, Milk Thistle, and Lactobacillus to Influence Plasma Bilirubin
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ClinicalTrials.gov Identifier: NCT04717726 |
Recruitment Status :
Completed
First Posted : January 22, 2021
Last Update Posted : July 28, 2023
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Tracking Information | |||||||||||||||
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First Submitted Date ICMJE | January 13, 2021 | ||||||||||||||
First Posted Date ICMJE | January 22, 2021 | ||||||||||||||
Last Update Posted Date | July 28, 2023 | ||||||||||||||
Actual Study Start Date ICMJE | February 24, 2021 | ||||||||||||||
Actual Primary Completion Date | July 19, 2023 (Final data collection date for primary outcome measure) | ||||||||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | |||||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||
Descriptive Information | |||||||||||||||
Brief Title ICMJE | Exercise, Milk Thistle, and Lactobacillus to Influence Plasma Bilirubin | ||||||||||||||
Official Title ICMJE | Milk Thistle and Lactobacillus Supplementation to Improve Exercise Outcomes in Obese Patients | ||||||||||||||
Brief Summary | The proposed clinical trial will test our hypothesis that, during exercise, red blood cell (RBC) release of heme and catabolism to bilirubin is an essential process that mediates gene responses that reduce body fat. We will evaluate whether Milk Thistle extract or Lactobacillus Gasseri extends bilirubin circulating times to decrease body fat further. Thus we will perform a 12-week, 6-armed trial with one group performing aerobic exercise 5 times per week (EX) one group receiving a Milk Thistle extract (MT), one group receiving a lactobacillus gasseri supplement (LAC), a group receiving only a placebo (CON), and groups both exercising and receiving the MT (MT + EX) and lactobacillus and exercise (LAC + EX). | ||||||||||||||
Detailed Description | The investigative team's previous work has shown that BR binds to the PPARalpha protein in fat and liver tissues to activate genes that improve fatty acid oxidation via a hormone known as fibroblast growth factor-21 (FGF21). The investigators recently showed that in high capacity running rats (HCR) compared to low capacity running (LCR), in which the latter are obese, BR levels and PPARalpha-FGF21 were significantly raised in the high-capacity runners. New investigations have shown that Milk Thistle (MT) herbal supplement contains polyphenols that activate pathways that suppress the glucuronyl enzyme UGT1A1 that removes BR from the blood, improving liver function and moderately increasing BR blood levels by ~2-fold. Similar findings have been demonstrated with Lactobacillus Gasseri supplementation. Hence, there is a bilirubin-PPARalpha-FGF21 axis that can be driven by exercise and dietary supplementation. We will test whether exercise and milk thistle or exercise and lactobacillus gasseri synergistically increase bilirubin-PPARalpha-FGF21, further reducing body fat in patients with obesity. Participants in the EX, EX + MT, and EX + LAC groups will complete five weekly exercise sessions on their own, expending roughly 600 kcal per session. Participants will be provided a Polar A-300 heart rate monitor programmed for their individual attributes (height, weight, age, training status, gender), which gives a real-time estimate of energy expenditure during exercise. Participants will report to the lab once per week to download the exercise sessions and verify compliance. If participants are not compliant (defined as completing 85% of their assigned exercise sessions per month), they will be disqualified. This intervention has been successfully used by the investigators in multiple studies to produce significant weight loss without dietary intervention in this population with a retention rate of over 90% Participants in the MT and EX + MT groups will be provided 900 mg of standardized milk thistle extract daily (300 mg three times per day before meals) over the 12-week regimen. The investigators will use the standardized Jarrow Formulas Milk Thistle Veggie Caps containing 30:1 extract that is standardized to contain 80% total Milk Thistle seed flavonoids (polyphenols), including the critical Silymarin fractions isosilybinins A and B, silybinins A and B, silychristin and silydianin that is active against suppressing the UGT1A1 enzyme increasing plasma bilirubin. The capsules are free of wheat, gluten, soybeans, dairy, egg, fish/shellfish, peanuts/tree nuts, and GMOs. Rationale for using this brand: There have been inconsistencies with previous studies that did not use a standardized silymarin extract, which may have contained low levels of the active polyphenolic flavonoids in the milk thistle plant, which varies in the plant's stems, leaves, roots, and flowers. Participants in the LAC and LAC + EX groups will receive two doses of 3 billion CFU of lactobacillus gasseri per day for a total of 6 billion CFU, the recommended upper level for supplementation of probiotic cultures. The Swanson brand Lactobacillus gasseri will be used, as these capsules are also free of wheat, gluten, soybeans, dairy, egg, fish/shellfish, peanuts/tree nuts, and GMOs. Importantly, this brand uses acid-resistant designed release capsules to improve the viability of the lactobacillus in the human stomach. Participants in the CON and EX group will receive a placebo (maltodextrin) made to look identical to the MT capsules. |
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Study Type ICMJE | Interventional | ||||||||||||||
Study Phase ICMJE | Phase 3 | ||||||||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: 6 armmed, placebo controlled RCT Masking: Double (Participant, Investigator)Masking Description: Participants nor research staff working with them will know what supplement they are receiving. Primary Purpose: Treatment
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Condition ICMJE | Obesity | ||||||||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||||
Recruitment Status ICMJE | Completed | ||||||||||||||
Actual Enrollment ICMJE |
42 | ||||||||||||||
Original Estimated Enrollment ICMJE |
30 | ||||||||||||||
Actual Study Completion Date ICMJE | July 19, 2023 | ||||||||||||||
Actual Primary Completion Date | July 19, 2023 (Final data collection date for primary outcome measure) | ||||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 50 Years (Adult) | ||||||||||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||||||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||||||||
Listed Location Countries ICMJE | United States | ||||||||||||||
Removed Location Countries | |||||||||||||||
Administrative Information | |||||||||||||||
NCT Number ICMJE | NCT04717726 | ||||||||||||||
Other Study ID Numbers ICMJE | 63147 | ||||||||||||||
Has Data Monitoring Committee | No | ||||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Kyle Flack, University of Kentucky | ||||||||||||||
Original Responsible Party | Same as current | ||||||||||||||
Current Study Sponsor ICMJE | Kyle Flack | ||||||||||||||
Original Study Sponsor ICMJE | University of Kentucky | ||||||||||||||
Collaborators ICMJE | Not Provided | ||||||||||||||
Investigators ICMJE | Not Provided | ||||||||||||||
PRS Account | University of Kentucky | ||||||||||||||
Verification Date | July 2023 | ||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |