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NCT Number: NCT05806801

Metabolic Adaptations to Weight Loss With and Without Exercise

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).

Recruiting

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Key information

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location status: Recruiting

Location contact

Jeff F Horowitz, PhD

PRINCIPAL_INVESTIGATOR

Suzette Howton

CONTACT

[email protected]

7346479850

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

MICT Exercise

Behavioral

Subjects randomized into this group will complete a moderate intensity continuous exercise 4 days/week.

No Exercise (Control)

Behavioral

Subjects randomized into this group will remain sedentary throughout the duration of the study.

Primary outcomes

  1. Insulin sensitivity

    Time frame: 2 hours

    a hyperinsulinemic-euglycemic clamp will be used to quantify peripheral insulin sensitivity

  2. Fatty acid turnover

    Time frame: 2 hours

    stable isotope tracer infusion methods will be used to assess fatty acid turnover

  3. Adipose tissue capillarization

    Time frame: 30 minutes

    measured immunohistochemically using an antibody for CD31, quantified using ImageJ software

  4. Adipose tissue fibrosis

    Time frame: 30 minutes

    measured histologically using Sirus Red Staining, quantified using ImageJ software

Secondary outcomes

  1. Body weight change

    Time frame: 6 months

    Change in body weight will be assessed 6 months after completing the 10% weight loss intervention

  2. Body fat mass

    Time frame: 30 minutes

    Body fat mass will be measured by Dual Energy X-ray Absorptiometry (DEXA)

  3. Oral Glucose Tolerance Test (OGTT)

    Time frame: 2 hours

    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

Study contacts

Contact information is provided by the study sponsor or research team.

Suzette M Howton

CONTACT

[email protected]

734-647-9850

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Registry information

Acronym: WAX

Important dates

Study start
2023
Primary completion
2027
Study completion
2028
First posted
Apr 10, 2023
Registry last updated
Apr 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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