The Influence of Physical Activity on the Gut Microbiome of Pre-Diabetic Adults

Study Overview
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Brief Summary
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The present study is a 100-participant randomized controlled 2-arm parallel trial that employs a metagenomic approach to examine how 8 weeks of supervised moderate-intensity treadmill walking exercise (MWE) for 30-45 min 3 times/week alters the gut microbiome, serum short chain fatty acids, and the cardiometabolic profile, body weight, and body composition of individuals 30-64 years old who have overweight or obesity and have prediabetes.

Detailed Description
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All eligible and consented participants will complete a 3-week run-in phase during which baseline outcome assessments will be performed. During run-in weeks 1 and 2, participants will wear a Fitbit Inspire 2 smartwatch and complete three unannounced dietary recalls. During the run-in week 3 (see table below), participants will consume their 3-day standardized meal plan on days three through five, obtain a fecal sample, complete a study questionnaire, and complete a study assessment visit. To quantify compliance with the 3-day meal plan, participants will be provided with a paper checklist of all foods to be consumed, and will be asked to indicate which foods were consumed and to document any deviation. The study assessment visit will include a fasting blood draw (at baseline and week eight only), blood pressure in triplicate, weight measure and body fat assessment in duplicate, and a saliva sample.

Official Title
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The Influence of Physical Activity on the Gut Microbiome of Pre-Diabetic Adults

Conditions
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Obesity, Overweight, Overweight and Obesity, PreDiabetes, Type 2 Diabetes, Type 2 Diabetes Mellitus, Type 2 Diabetes Mellitus in Obese

Intervention / Treatment
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* Behavioral: Physical Activity Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Classified as overweight or obese with BMI 25.0-39.9 kg/m2. Documentation* of a prediabetes diagnosis within one year of enrollment by physician or primary care provider based on lab tests showing a fasted blood glucose of 100-125 mg/dL, a 2-hour oral glucose tolerance test of 140-199 mg/dL, or an HbA1c level of 5.7%-6.4%76; OR a study screening lab value of HbA1C within the afore mentioned range. Currently engaged in <100 min/week of physical activity - confirmed by questionnaire. No exercise contraindications as assessed by the Physical Activity Readiness Questionnaire (PAR-Q)78-this Questionnaire involves seven yes or no questions regarding an individual's health status, with answering yes to any one of these questions requiring a prospective participant to acquire a written doctor's note stating they can safely participate in the trial's exercise intervention. No self-reported physical/mental disabilities or gastrointestinal conditions. No antibiotic usage within the last 45 days. Stable weight over the last 6 months (<10% change). Not currently pregnant, planning to become pregnant, or currently breastfeeding. Willing to maintain current dietary and exercise habits, aside from any changes to be made per the study exercise protocol. Note: Documentation can include either a print out or screen shot of the lab value illustrating eligibility, along with the date of the test and the participant's name. If a hard copy is provided, the date and name will be redacted. Exclusion Criteria: Self-reported use of metformin and/or other medications that could interfere with the primary outcome. History of bariatric surgery or a history of other medical interventions that would interfere with the primary outcome.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Participants in this group will complete the physical activity intervention. | Behavioral: Physical Activity Intervention<br>* Three walking sessions/week for a total of 8 weeks (24 total sessions) - Walking sessions will either take place on new commercial treadmills in the Epidemiology Clinical Research Center or remotely at or around a participant's home. Regardless of the walking location, walking sessions will be 30 min in duration during intervention weeks 1 through 4 and a minimum of 45 min each during intervention weeks 5 through 8.<br>|
| No Intervention: Control Group<br>Participants in this group will be asked to maintain their normal level of physical activity. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Shannon Index | Changes to the gut microbiome will be assessed via metagenomic sequencing, from pre- to post-intervention. The Shannon Index-a measure of microbial community diversity-will be the primary indicator for changes in gut microbiota composition, and will be assessed at baseline, and following the 4th and 8th weeks. Index values are unitless and range from 0 to 1. Lower values indicate more diversity while higher values indicate less diversity. Outcome will be reported at baseline, 4 weeks, and 8 weeks and as the change from baseline to 4 weeks and baseline to 8 weeks. | 8 weeks | 
| Chain in Serum Short Chain Fatty Acids (SCFA) | Participants will undergo fasted blood draws to assess serum SCFA levels. This work will be performed using the Metabolon pipeline. Outcome is reported as the serum concentrations of acetate, propionate, and butyrate individually and sum of all SCFAs in units of ng/ml. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High-density lipoprotein cholesterol (HDL-C) | High-density lipoprotein cholesterol (HDL-C) will be measured using standard laboratory test and report in units of mg/dl. | 8 weeks | 
| Triglycerides | Blood triglycerides will be measured using a standard laboratory test and reported in units of mg/dl. | 8 weeks | 
| Fasting Insulin | Fasting insulin will be measured by laboratory test and reported in units of uIU/ml. | 8 weeks | 
| Fasting Glucose | Fasting insulin will be measured by standard laboratory test and reported in units of mg/dl. | 8 weeks | 
| C-reactive Protein (CRP) | C-reactive protein (CRP) will be measured by laboratory test and reported in units of mg/l. | 8 weeks | 
| Resting Blood Pressure (BP) | Resting systolic and diastolic blood pressures will be reported in units of mmHg. | 8 weeks | 
| Hemoglobin A1C (HbA1c) | Hemoglobin A1C (HbA1c) will be measured by laboratory test. This is a unitless measure. | 8 weeks | 
| Body Composition | Body composition will be analyzed using bioelectrical impedance. Outcome will be reported as percent body fat. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbiome, Physical Activity