Exercise, Milk Thistle, and Lactobacillus to Influence Plasma Bilirubin

NCT04717726 | Completed Phase 3

• 1 other identifier: 63147
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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).

Conditions

Obesity

Keywords

Exercise; weight loss; obesity; Lactobacillus; Milk Thistle; Bilirubin

Outcome Measures

Primary Outcomes (12)

• Lean mass

  kg of lean mass will be assessed by air displacement plethysmography (BodPod, Cosmed USA)

  baseline (prior to initiation of study)

• Lean mass

  kg of lean mass will be assessed by air displacement plethysmography (BodPod, Cosmed USA)

  12 weeks (immediately after 12 week exercise and/or supplement intervention)

• Fat mass

  kg of fat mass will be assessed by air displacement plethysmography (BodPod, Cosmed USA)

  baseline (prior to initiation of study)

• Fat mass

  kg of fat mass will be assessed by air displacement plethysmography (BodPod, Cosmed USA)

  12 weeks (immediately after 12 week exercise and/or supplement intervention)

• Plasma bilirubin

  Plasma bilirubin will be assessed in the fasted state

  baseline (prior to initiation of study)

• Plasma bilirubin

  Plasma bilirubin will be assessed in the fasted state

  12 weeks (immediately after 12 week exercise and/or supplement intervention)

• Plasma FGF21

  fibroblast growth factor-21 will be assessed in the fasted state

  baseline (prior to initiation of study)

• Plasma FGF21

  fibroblast growth factor-21 will be assessed in the fasted state

  12 weeks (immediately after 12 week exercise and/or supplement intervention)

• Red blood cell count

  Red blood cell count will be assessed in the fasted state

  baseline (prior to initiation of study)

• Red blood cell count

  Red blood cell count will be assessed in the fasted state

  12 weeks (immediately after 12 week exercise and/or supplement intervention)

• Urobilin

  Plasma Urobilin will be assessed in the fasted state

  baseline (prior to initiation of study)

• Urobilin

  Plasma Urobilin will be assessed in the fasted state

  2 weeks (immediately after 12 week exercise and/or supplement intervention)

Secondary Outcomes (2)

• Liver function

  baseline (prior to initiation of study)

• Liver function

  12 weeks (immediately after 12 week exercise and/or supplement intervention)

Study Arms (6)

MT

EXPERIMENTAL

Participants in the MT group will be supplemented with Milk Thistle extract for 12 weeks

Dietary Supplement: Milk Thistle (MT)

LAC

EXPERIMENTAL

Participants in the LAC group will be supplemented with Lactobacillus Gassri for 12 weeks

Dietary Supplement: Lactobacillus Gasseri (LAC)

EX

EXPERIMENTAL

Participants in the EX group will perform aerobic exercise, 5 days per week for 12 weeks

Behavioral: Exercise (EX); Dietary Supplement: Control (CON)

MT + EX

EXPERIMENTAL

Participants in the MT + EX group will be supplemented with Milk Thistle extract and exercise for 12 weeks

Dietary Supplement: Milk Thistle (MT); Behavioral: Exercise (EX)

LAC + EX

EXPERIMENTAL

Participants in the LAC + EX group will be supplemented with Lactobacillus Gassri and exercise for 12 weeks

Dietary Supplement: Lactobacillus Gasseri (LAC); Behavioral: Exercise (EX)

CON

PLACEBO COMPARATOR

Participants in the CON group will be supplemented with maltodextrin pills made to look like the pills received by the MT and LAC groups for 12 weeks

Dietary Supplement: Control (CON)

Interventions

Milk Thistle (MT) DIETARY_SUPPLEMENT

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. We 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.

MT; MT + EX

Lactobacillus Gasseri (LAC) DIETARY_SUPPLEMENT

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. We will use Swanson brand Lactobacillus gasseri, whose 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.

LAC; LAC + EX

Exercise (EX) BEHAVIORAL

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 Dr. Flack in multiple studies to produce significant weight loss without dietary intervention in this population with a retention rate of over 90%

EX; LAC + EX; MT + EX

Control (CON) DIETARY_SUPPLEMENT

Participants in the CON and EX group will receive a placebo (maltodextrin) made to look identical to the MT and LAC capsules.

CON; EX

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Classified as obese (BMI 30-45)
• Sedentary (do not currently exercise)
• Aged 18-50 years
• Without contraindications to exercise

You may not qualify if:

• Dieting for weight control
• Tobacco users
• Have a ragweed allergy
• Taking antibiotics, hypoglycemic agents, anticoagulants, statins, or NSAIDs
• Nursing, pregnant, or planning on becoming pregnant
• Supplementing with a probiotic

Sponsors & Collaborators

• Kyle Flack: lead

Study Sites (1)

University of Kentucky- Nutrition Assessment Lab

Lexington, Kentucky, 40506, United States

Location

MeSH Terms

Conditions

Obesity; Motor Activity; Weight Loss

Interventions

milk-thistle extract; 6-phospho-beta-galactosidase; Exercise

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Body Weight Changes

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants nor research staff working with them will know what supplement they are receiving.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant professor

Model Details: 6 armmed, placebo controlled RCT

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 22, 2021
• Study Start: February 24, 2021
• Primary Completion: July 19, 2023
• Study Completion: July 19, 2023
• Last Updated: July 28, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Within 6 months of study completion data, for 5 years.
• Access Criteria: available to public, has not been created yet

Locations

US (1)