Metabolic Adaptations to Weight Loss With and Without Exercise (WAX)

Study Purpose:

The combination of caloric restriction and exercise is the most common first-line treatment for obesity-related disorders, yet we know very little about how these two very different treatments work together. A deeper understanding about mechanisms underlying the health benefits of adding exercise to a weight loss program will not only aid efforts to optimize more effective lifestyle interventions, but it can also uncover novel targets for the treatment/prevention of obesity-related diseases.

Although a reduction in body fat is the fundamental adaptation to weight loss, we know almost nothing about the effects that adding exercise has on structural and functional changes within fat tissue that may further enhance metabolic health. This is very important because many obesity-related metabolic health complications are tightly linked with abnormalities in abdominal fat tissue. We argue exercise-induced modifications in abdominal fat tissue will reveal persistent health benefits even if some weight is regained

Study Summary:

10% Weight Loss Phase - Subject participation in the study will involve a series of metabolic tests before, at midpoint, and after undergoing a 10% weight loss program (with or without exercise training depending on group randomization). During this, subjects will be randomized into one of two different experimental groups:

1. Moderate Intensity Continuous Training (MICT) exercise group
2. No exercise (control) group

Follow-up Phase: After completing the metabolic testing post-weight loss, all study-related diet and exercise supervision will end and subjects will be free to make their own choices regarding diet and exercise/physical activity behavior. Subjects will then be asked to complete follow-up testing at 2-, 4- and 6- months post-weight loss.

Total involvement in the study for each subject will likely be about 10-13 months (4-7 months during weight loss phase, 6 months during follow-up phase).

Study Overview

• Status: Recruiting
• Conditions: Obesity; Metabolic Syndrome; Insulin Resistance; Weight Loss; Insulin Sensitivity; Metabolic Disease
• Intervention / Treatment: Behavioral: MICT Exercise; Behavioral: No Exercise (Control)

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Suzette M Howton; Phone Number: 734-647-9850; Email: suzetter@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Suzette Howton; Phone Number: 734-647-9850; Email: suzetter@med.umich.edu
      • Principal Investigator: Jeff F Horowitz, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria

• Age: 18-40
• Body Mass Index: 30-40 kg/m2
• Weight stable (±3kg for greater than or equal to about 2 months)
• No regularly planned exercise/physical activity
• Women must have regularly occurring menses and must be premenopausal

Exclusion criteria

• EKG abnormalities
• Evidence/history of cardiovascular disease, diabetes or other metabolic disease
• Medications known to affect lipid or glucose metabolism
• Pregnant or lactating
• Tobacco or e-cigarette use
• Prior experience of hypersensitivity to insulin, human albumin, and potassium chloride injection.
• Allergies/hypersensitivity to local anesthetics of the amide type (e.g., lidocaine)
• History of hyperkalemia or potential for developing hyperkalemia (including but not limited to taking drugs that may induce hyperkalemia such as cardiac glycosides or potassium sparing diuretics)
• Anti-coagulant medication (e.g., Coumadin, Rivaroxaban) and Lidocaine allergy/sensitivity are exclusion criteria for the biopsy procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate Intensity Continuous Training (MICT) exercise group; 45 minutes of continuous steady-state exercise at 70% maximal heart rate throughout the 10% weight loss phase of the study	Behavioral: MICT Exercise; Subjects randomized into this group will complete a moderate intensity continuous exercise 4 days/week.
Experimental: No exercise (Control); to remain sedentary (no planned physical exercise) throughout the duration of the 10% weight loss phase of the study	Behavioral: No Exercise (Control); Subjects randomized into this group will remain sedentary throughout the duration of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	a hyperinsulinemic-euglycemic clamp will be used to quantify peripheral insulin sensitivity	2 hours
Fatty acid turnover	stable isotope tracer infusion methods will be used to assess fatty acid turnover	2 hours
Adipose tissue capillarization	measured immunohistochemically using an antibody for CD31, quantified using ImageJ software	30 minutes
Adipose tissue fibrosis	measured histologically using Sirus Red Staining, quantified using ImageJ software	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight change	Change in body weight will be assessed 6 months after completing the 10% weight loss intervention	6 months
Body fat mass	Body fat mass will be measured by Dual Energy X-ray Absorptiometry (DEXA)	30 minutes
Oral Glucose Tolerance Test (OGTT)	A test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood will be completed at each clinical visit appointment	2 hours

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Jeffrey Horowitz, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: March 28, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Hyperinsulinism; Body Weight Changes; Metabolic Syndrome; Weight Loss; Insulin Resistance; Body Weight; Metabolic Diseases
• Other Study ID Numbers: HUM00220220

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No