Influence of Exercise on the Gut Microbiome of Overweight and Obese Adults With Prediabetes

PreDiabetes Clinical Trial

Official title:

Influence of Exercise on the Gut Microbiome of Overweight and Obese Adults With Prediabetes

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04124354
• Other study ID #: STUDY00007532
• Status: Terminated
• Phase: N/A
• Start date: February 10, 2020
• Est. completion date: August 31, 2020

Study information

• Verified date: July 2021
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Purpose: The investigators propose a 20-participant randomized 2-arm parallel trial with a delayed-intervention control examining how 8 weeks of moderate-intensity walking exercise alters the gut microbiome, short chain fatty acid (SCFA)-producing taxa, and the cardiometabolic profile and body weight of individuals who are overweight or obese and have prediabetes (PreD).

Aim 1: Examine and compare exercise-related shifts in the gut microbiome of individuals with PreD.

Aim 2: Examine and compare exercise-related changes in SCFA-producing taxa.

Exploratory Aim: Examine what percentage of the exercise-related changes observed in participants' gut microbiome and SCFA-producing taxa mediate changes in their cardiometabolic profile and body weight.

Description:

In the U.S, 91.8 million adults have PreD. Preventing progression of PreD to type 2 diabetes (T2D) is vital. Odds of cardiovascular disease are higher among those with T2D, with $327 billion/year spent treating T2D. Major scientific organizations have thus called for studies of novel intermediates connecting health behaviors to pre-clinical cardiometabolic disease (CMD; e.g., PreD) to lower future clinical disease risk. Physical activity (PA) is key modifiable determinant of good health. PA recommendation adherence is associated with a 25-35% dose-dependent reduction in all-cause mortality, with as little as 75 min/week of regular moderate-intensity PA beneficial. In fact, an intervention within the Diabetes Prevention Program emphasizing PA participation at recommended levels was as successful as Metformin in preventing incident T2D-likely partially due to a 5kg-reduction in body weight during this trial. Yet, PA's impact on disease risk reduction is not explained entirely by CMD risk factors or weight loss, with mechanistic pathways still unclear and crucial to examine. The gut microbiota and microbiome have been posited as mechanistic intermediates linking PA to attenuated CMD development. However, there is no known research which has examined exercise-related changes in the human gut microbiome or SCFA-producing taxa in a population with a pre-clinical CMD such as PreD and how these changes mediate changes in CMD indices and body weight.

The proposed project is therefore innovative for a least two reasons. First, as stated, the investigators know of no study in individuals with PreD which examined how a moderate-intensity walking program may modify the gut microbiome and SCFA-producing taxa. Second, the investigators will use formal mediation analyses to examine the degree to which exercise-related changes in the gut microbiome and SCFA-producing taxa explain changes observed in CMD indices and body weight. These exploratory analyses will allow for a deeper interpretation of the physiological mechanisms by which exercise may improve health and inform future trial construction. Indeed, this study will provide critical preliminary evidence for a larger NIH R01-funded trial submitted to the NIDDK, NHLBI, or NCI, with the NIH committed to funding innovative scientific proposals involving the microbiome. The investigators will use this trial's observations to determine: 1) which taxa within the gut microbiome are most impacted by moderate-intensity walking; 2) the intra- and inter-person variability of gut microbiota changes due to moderate-intensity walking; and 3) whether the fixed frequency, intensity, and duration of the walking implemented results in meaningful changes. Observations in relation to these points will inform the design and implementation of future interventions to reduce pre-clinical disease states like PreD in a mechanistically-informed manner.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: August 31, 2020
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 64 Years

Eligibility

Inclusion Criteria:

• Classified as overweight or obese with BMI 25.0-39.9 kg/m2

• Diagnosis of prediabetes as classified by a fasted blood glucose of 100 - 125 mg/dL, 2-hour oral glucose tolerance test of 140 - 199 mg/dL, or HbA1C level of 5.7% - 6.5%

• Currently engaged in < 150 minutes/week of physical activity-confirmed via the Modifiable Activity Questionnaire

Exclusion Criteria:

• Individuals with contraindications to exercise participation as assessed by the Physical Activity Readiness Questionnaire

• Self-reported physical/mental disabilities or gastrointestinal conditions

• Antibiotic usage within the last 45 days

Related Conditions & MeSH terms

• Glucose Intolerance
• Overweight
• PreDiabetes
• Prediabetic State

Intervention

Behavioral:
• Physical Activity
Participants will attend 3 treadmill walking sessions/week for 8 weeks (24 total)-exercising at 60-75% of their heart rate (HR) reserve monitored using Polar FT1 HR monitors. All walking sessions will take place using treadmills within the West Bank Office Building on the UMN-Twin Cities campus. Each walking session will be 30 min long during intervention weeks 1-4 and 45 min each during weeks 5-8. This exercise dose is equivalent to that employed in the only two human studies of exercise and the gut microbiome in addition to the dosage observed necessary to yield meaningful cardiometabolic changes. After the 4th- and 8th-weeks of the intervention, participants in both study groups will again undergo outcome assessments

Locations

Country	Name	City	State
United States	Epidemiology Clinical Research Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Shannon Index (Alpha-Diversity) as Reflected in Change in Operational Taxonomic Units	Alpha diversity is the mean species diversity of a local site, which, in this study, is the fecal sample provided by participants used as a proxy for sampling the gut microbiome. The Shannon Index is based on the weighted geometric mean of the proportional abundances of the types of microbes. Change in alpha diversity will be reported as change in operational taxonomic units (OTUs).	Baseline, 8 weeks
Secondary	Change in Plasma LDL Concentrations	Participants will have blood drawn after fasting over night or for at least 8 hours. Plasma low density lipoprotein (LDL) concentrations will be determined using standard laboratory assay methods. Concentrations will be reported in mg/dl.	Baseline, 8 weeks
Secondary	Change in Plasma HDL Concentrations	Participants will have blood drawn after fasting over night or for at least 8 hours. Plasma high density lipoprotein (HDL) concentrations will be determined using standard laboratory assay methods. Concentrations will be reported in mg/dl.	Baseline, 8 weeks
Secondary	Change in Plasma Total Cholesterol Concentrations	Participants will have blood drawn after fasting over night or for at least 8 hours. Plasma total cholesterol concentrations will be determined using standard laboratory assay methods. Concentrations will be reported in mg/dl.	Baseline, 8 weeks
Secondary	Change in Plasma Insulin Concentrations	Participants will have blood drawn after fasting over night or for at least 8 hours. Plasma insulin concentrations will be determined using standard laboratory assay methods. Concentrations will be reported in mmol/l.	Baseline, 8 weeks
Secondary	Change in Plasma Glucose Concentrations	Participants will have blood drawn after fasting over night or for at least 8 hours. Plasma glucose concentrations will be determined using standard laboratory assay methods. Concentrations will be reported in mg/dl.	Baseline, 8 weeks
Secondary	Change in Plasma CRP Concentrations	Participants will have blood drawn after fasting over night or for at least 8 hours. Plasma C-reactive protein (CRP) concentrations will be determined using standard laboratory assay methods. Concentrations will be reported in mg/l.	Baseline, 8 weeks
Secondary	Change in Resting Blood Pressure - Systolic	Resting blood pressure will be measured using an Omron Automatic BP Cuff and reported in mmHG.	Baseline, 8 weeks
Secondary	Change in Resting Blood Pressure - Diastolic	Resting blood pressure will be measured using an Omron Automatic BP Cuff and reported in mmHG.	Baseline, 8 weeks
Secondary	Change in Waist Circumference	Waist circumference will be measured using anthropometric tape and reported in cm.	Baseline, 8 weeks
Secondary	Change in Body Weight	Body weight will be measured using a Tanita Body Composition and Weight scale and reported in kg.	Baseline, 8 weeks
Secondary	Change in Body Fat Percentage	Body fat percentage will be measured using a Tanita Body Composition and Weight scale and reported as a percentage.	Baseline, 8 weeks