Exercise for Obesity

Overseen By Robert C Hickner, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Florida State University

Must be taking: Estrogen/progestin contraceptives

Must not be taking: NSAIDs, SSRIs

Disqualifiers: Diabetes, Hypertension, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 8 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Impaired endothelial function is observed in disease states related to obesity, such as atherosclerosis, coronary artery disease, and diabetes. Reactive oxygen species (ROS) production and resultant oxidative stress contribute to the development of these obesity-related diseases. The enzyme NADPH-oxidase is a major source of oxidative stress within the vasculature, and has been linked with the Metabolic Syndrome. In the investigator's previously funded studies, the investigators demonstrated for the first time that: 1) in vivo ROS were elevated in skeletal muscle of obese as compared to lean or overweight human subjects, 2) perfusion of the NADPH-oxidase inhibitor apocynin locally into muscle normalized ROS levels and reversed local microvascular endothelial dysfunction in the obese individuals, and 3) aerobic exercise training was effective at attenuating in vivo hydrogen peroxide production and reversing microvascular endothelial dysfunction in the obese individuals. The investigators will investigate in this R15 renewal application the mechanism of exercise training-induced alterations in ROS production and action on endothelial dysfunction in obesity using our newly developed microdialysis methodology of monitoring ROS production, in combination with analysis of muscle biopsy samples obtained before and after our previously tested 8-week intervention of aerobic interval exercise training. The objectives of this study are to determine the impact of in vivo NADPH oxidase activity on endothelial function in obese individuals, and to determine the mechanism of training-induced improvements in endothelial function. The investigator's unique microdialysis methodology will allow monitoring of microvascular/endothelial function and ROS generation, as well as the administration of pharmacological agents directly into muscle. The central hypothesis is that it is upregulation of both mitochondrial ROS and NADPH oxidase-derived ROS that results in endothelial dysfunction in obesity, and that exercise training down-regulates mitochondrial-derived ROS, and NADPH oxidase 4, thereby improving endothelial function. The aims of this proposal are to: 1) determine the contributions of mitochondrial ROS and specific NADPH oxidase isoforms to the NADPH oxidase dependent endothelial dysfunction in skeletal muscle of obese individuals; 2) determine the mechanism of ROS reduction and improved endothelial function resulting from an 8-week aerobic interval training program.

Will I have to stop taking my current medications?

The trial requires that participants not take medications that affect circulation, nonsteroidal anti-inflammatory drugs, or serotonin reuptake inhibitors. If you are on these medications, you may need to stop taking them to participate.

Is exercise safe for people with obesity?

Exercise is generally safe for people with obesity and offers many health benefits, such as improved cardiovascular health and better weight management. However, it's important to tailor the type and intensity of exercise to individual needs and consult with healthcare professionals to ensure safety. ^{1 2 3 4 5}

How does exercise as a treatment for obesity differ from other treatments?

Exercise for obesity is unique because it not only helps with weight and fat loss but also improves overall fitness and health, even if weight loss is modest. Unlike other treatments, exercise can enhance cardiovascular health, increase muscle strength, and improve quality of life, making it an essential part of managing obesity. ^{1 3 5 6 7}

What data supports the effectiveness of the treatment Exercise, Physical Activity, Workout, Fitness Training for obesity?

Research shows that exercise helps people with obesity by improving physical performance, quality of life, and reducing body weight and fat mass. It also enhances cardiovascular health and helps maintain muscle strength during weight loss. ^{3 5 8 9 10}

Who Is on the Research Team?

Robert C Hickner, PhD

Principal Investigator

Florida State University

Are You a Good Fit for This Trial?

This trial is for premenopausal women who are obese, sedentary, and have been weight stable for the last 6 months. They must meet at least three criteria of Metabolic Syndrome such as a large waist size or high blood pressure. Participants should not be taking certain medications or supplements that affect circulation or oxidative stress.

Inclusion Criteria

I am using a combined hormonal contraceptive method.

Sedentary obese individuals will have the Metabolic Syndrome as defined according to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

I am a woman and have not gone through menopause.

Exclusion Criteria

I am on medication that could affect my blood flow.

I do not have conditions like severe arthritis, Parkinson's, or paralysis that would stop me from doing exercise tasks.

Individuals who smoke or chew tobacco

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Testing

Subjects undergo baseline testing including medical history, physical examination, and screening for cardiovascular disease and type 2 diabetes.

1-2 weeks

1 visit (in-person)

Treatment

Participants undergo 8 weeks of aerobic interval exercise training, with microdialysis experiments conducted before and after the training period.

8 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for changes in muscle blood flow and reactive oxygen species levels after the exercise training.

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Exercise

Trial Overview The study tests how an 8-week aerobic interval exercise program affects obesity-related endothelial dysfunction by reducing oxidative stress in muscles. It explores the role of NADPH oxidase activity and mitochondrial ROS in improving vascular health through exercise.

How Is the Trial Designed?

Group I: Exercise training Experimental Treatment 1 Intervention

Eight weeks of interval exercise training

Who Is Running the Clinical Trial?

Florida State University

Lead Sponsor

Trials

234

Recruited

41,100+

Published Research Related to This Trial

Exercise has numerous benefits for individuals with obesity, including aiding in weight loss and improving cardiovascular health, but the direct impact on weight loss from exercise alone is modest, typically resulting in only a few kilograms of weight loss.

Physical activity is crucial for managing type 2 diabetes and preventing its complications, and a structured approach like the 5 A's strategy can help healthcare professionals effectively support patients in overcoming barriers to increasing their physical activity levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity in management of persons with obesity. Oppert, JM., Bellicha, A., Ciangura, C.[2021]

A systematic review of 116 studies found that both aerobic and anaerobic training significantly improve body composition and physical fitness in individuals with obesity, with effect sizes ranging from trivial to very large.

Physical training not only reduces body weight and fat mass but also increases fat-free mass and VO2max, indicating enhanced cardiovascular fitness, suggesting that various intensities of exercise can be beneficial for weight loss and overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of physical training on anthropometrics, physical and physiological capacities in individuals with obesity: A systematic review. Zouhal, H., Ben Abderrahman, A., Khodamoradi, A., et al.[2021]

A structured, home-based exercise program significantly improved physical performance and quality of life in patients with obesity, as demonstrated by a cohort of 151 participants over a 3-month period.

After the program, participants showed notable enhancements in walking distance, speed, and VO2max, indicating that even simple exercise routines can have substantial health benefits for individuals with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of an Easy, Structured, and Home-Based Exercise Program to Improve Physical Performance and Quality of Life in a Patient's Cohort with Obesity. López-López, CO., Montes Castillo, ML., Aguilar-Serralde, CA., et al.[2023]

Physical activity is crucial for treating obesity, as it not only helps reduce fat but also prevents the loss of muscle mass and improves cardiovascular health, making it more than just a weight loss tool.

Successful physical activity programs for obese individuals require careful consideration of the type, intensity, duration, and frequency of exercise, along with addressing real-life barriers such as time constraints and lack of support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physical activity in the treatment of obesity]. Svacinová, H., Matoulek, M.[2010]

In a 12-week study involving 38 obese patients, those receiving weekly encouragement from personal trainers showed significant improvements in physical activity levels, pain reduction, and overall health status compared to a control group.

While there was no significant change in body weight, the structured physical activity program led to enhanced quality of life for the participants, highlighting the importance of behavioral changes in managing obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PHYSICAL ACTIVITY, QUALITY OF LIFE AND BODY IMAGE OF CANDIDATES TO BARIATRIC SURGERY. Barreto, BLM., Lima, JS., Albuquerque, DB., et al.[2019]

A systematic review of 13 studies found that both aerobic and strength exercises are crucial for effectively treating individuals with morbid obesity, whether they are undergoing medical or surgical interventions.

It is essential to tailor the volume and intensity of exercise programs to ensure patient adherence, highlighting the need for individualized exercise plans for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical exercise and morbid obesity: a systematic review. Fonseca-Junior, SJ., Sá, CG., Rodrigues, PA., et al.[2019]

Combining physical exercise with energy restriction diets leads to greater weight loss than exercise alone, making it the most effective strategy for significant weight loss.

Engaging in at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise weekly, along with resistance training, is recommended for weight loss and maintenance, which also helps improve obesity-related health issues like diabetes and cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity and physical exercise. Celik, O., Yildiz, BO.[2021]

This randomized controlled trial will assess the impact of exercise training combined with a very low energy diet (VLED) on body composition and health outcomes in 60 clinically severe obese women over 12 months.

The study aims to provide evidence on whether adding exercise to a VLED can lead to greater improvements in physical function, quality of life, and cardiometabolic risk factors compared to diet alone, addressing a gap in research for class II and III obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The functional and clinical outcomes of exercise training following a very low energy diet for severely obese women: study protocol for a randomised controlled trial. Miller, CT., Fraser, SF., Selig, SE., et al.[2018]

Exercise can be beneficial for obese individuals, but many are unable to tolerate physical activity due to their weight, which limits their ability to gain fitness and improve body composition.

The most effective treatment for obesity combines dietary restriction and exercise, with a greater emphasis on diet for those with severe obesity and a focus on exercise for managing mild obesity or preventing weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exercise on obesity. Garrow, JS.[2019]

Regular exercise is crucial for managing obesity, contributing to weight loss, maintenance, and improved metabolic health, with endurance training being the most effective type of exercise.

Higher levels of physical activity are associated with better weight loss maintenance, although establishing a direct cause-and-effect relationship remains challenging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise in the management of obesity. Petridou, A., Siopi, A., Mougios, V.[2019]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Physical activity in management of persons with obesity. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Effects of physical training on anthropometrics, physical and physiological capacities in individuals with obesity: A systematic review. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Usefulness of an Easy, Structured, and Home-Based Exercise Program to Improve Physical Performance and Quality of Life in a Patient's Cohort with Obesity. [2023]

4. Czech Republic pubmed.ncbi.nlm.nih.gov

[Physical activity in the treatment of obesity]. [2010]

5. Brazil pubmed.ncbi.nlm.nih.gov

PHYSICAL ACTIVITY, QUALITY OF LIFE AND BODY IMAGE OF CANDIDATES TO BARIATRIC SURGERY. [2019]

6. Brazil pubmed.ncbi.nlm.nih.gov

Physical exercise and morbid obesity: a systematic review. [2019]

7. Italy pubmed.ncbi.nlm.nih.gov

Obesity and physical exercise. [2021]

8. England pubmed.ncbi.nlm.nih.gov

The functional and clinical outcomes of exercise training following a very low energy diet for severely obese women: study protocol for a randomised controlled trial. [2018]

9. Sweden pubmed.ncbi.nlm.nih.gov

Effect of exercise on obesity. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Exercise in the management of obesity. [2019]