Effects of Obesity and Intensity of Exercise on Ghrelin Levels

Sponsor

University of Virginia (Other)

Overall Status

Recruiting

CT.gov ID

NCT04581980

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

44.6

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is investigating the effect of different intensities of exercise on levels of the hormone, ghrelin. In addition, we will be examining the relationship between any exercise induced changes in ghrelin and insulin sensitivity, obesity, and vascular function.

Condition or Disease	Intervention/Treatment	Phase
Obesity Insulin Resistance Cardiovascular Risk Factor	Other: Exercise	N/A

Detailed Description

Obesity increases the risk of disease. We will examine the impact of moderate and high intensity exercise on the hormone ghrelin and its two forms, acyl (AG) and des-acyl (DAG), which are suggested to influence appetite, glucose metabolism and vascular function. We will determine whether differential changes in total ghrelin, AG and DAG are associated with changes in appetite, insulin sensitivity and vascular function. Subjects will be categorized as; either lean or obese (BMI), and either normal fasting glucose or impaired glucose tolerant (oral glucose tolerance test). Each participant will undergo body composition analysis, and a maximal treadmill cardiopulmonary exercise test to determine lactate threshold and maximal oxygen uptake. Subjects will then complete three randomly assigned exercise sessions: a) control (rest), (b) moderate intensity exercise and, (c) high intensity exercise. Blood sampling and measures of vascular function will occur before, during and after each study. An ANOVA with repeated measures and logistic regression analyses will examine the differential impact of exercise intensity on the outcome measures. Data collected will be used to develop a precision exercise approach to treat obesity and abnormal glucose metabolism for a NIH grant submission. This project is related to the UVa emphasis in precision medicine.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Randomized, crossover designRandomized, crossover design

Masking:

None (Open Label)

Primary Purpose:

Health Services Research

Official Title:

Modulation of Ghrelin Release by Exercise Intensity: The Role of Obesity and Prediabetes Status

Actual Study Start Date :

Oct 14, 2020

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control This arm will receive no exercise
Experimental: Moderate Intensity Exercise This group will exercise on a treadmill at moderate intensity. Moderate intensity will be defined by the lactate threshold. A heart rate monitor will be utilized at all times to record heart rate.	Other: Exercise Participants will exercise on a cycle ergometer
Experimental: High Intensity Exercise This group will exercise on a treadmill at high intensity. High intensity will be defined by an by 75% of the difference between the lactate threshold and peak.	Other: Exercise Participants will exercise on a cycle ergometer

Arm

Intervention/Treatment

No Intervention: Control

This arm will receive no exercise

Experimental: Moderate Intensity Exercise

This group will exercise on a treadmill at moderate intensity. Moderate intensity will be defined by the lactate threshold. A heart rate monitor will be utilized at all times to record heart rate.

Other: Exercise

Participants will exercise on a cycle ergometer

Experimental: High Intensity Exercise

This group will exercise on a treadmill at high intensity. High intensity will be defined by an by 75% of the difference between the lactate threshold and peak.

Other: Exercise

Participants will exercise on a cycle ergometer

Outcome Measures

Primary Outcome Measures

Ghrelin [Measured at 6 timepoints over 2-3 hours during each experimental visit]
We will be analyzing plasma levels of acylated and deacylated ghrelin

Secondary Outcome Measures

Appetite Questionnaire (VAS) [Measured at 6 timepoints over 2-3 hours during each experimental visit]
We will see how appetite may or may not change in response to exercise
Vascular Function (brachial flow mediated dilation) [Measured at 5 timepoints over 2-3 hours during each experimental visit]
We will be measuring how the arteries respond (i.e. dilate) in response to exercise

Other Outcome Measures

Insulin Sensitivity [Insulin and glucose will be collected at 5 timepoints during the OGTT, and 11 timepoints during each testing visit. The Matsuda index (mathematical model) will be used to calculate insulin sensitivity]
We want to create a linear regression model to explore the relationship between exercise induced changes in ghrelin and insulin sensitivity
Body Composition [Body composition will be measured twice during a DEXA and CT scan (takes about 30 minutes)]
We want to create a linear regression model to explore the relationship between exercise induced changes in ghrelin and body composition (i.e. fat mass)

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

40-52 years of age
BMI between 18-35 kg/m2
Untrained (reports less than 2 days/week of exercise)
Weight stable (no significant loss/gain of more than 3kg in the past 3 months)
Females must be premenopausal and report normal menstrual cycles

Exclusion Criteria:

History of diabetes, gastrointestinal disease, or endocrine disorder
Smoking (must have quit at least 6 months prior)
Disordered eating
Females currently pregnant or undergoing fertility treatments
The following medications (due to their effect on insulin sensitivity ,endothelial function and/or ghrelin secretion): Synthetic growth hormone, metformin, synthetic insulin, sulfonylureas, meglitinides, Thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors , biguanides, alpha-glucosidase inhibitors, phosphodiesterase inhibitors, beta-blockers, alpha-blockers, ACE-inhibitors, ARB's, fibrates, glucocorticoids, olanzapine