Effects of a Calorie Restricted, Very Low Fat Plant-based Diet and Multi-component Exercise Program on Metabolic Health

NCT ID: NCT02706288

Last Updated: 2022-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2022-12-31

Brief Summary

The purpose of this study is to understand how weight loss by a very low fat plant-based diet with an exercise program affects metabolic and cardiovascular health in overweight adults at high risk for disease. Outcome measures will include assessment of insulin sensitivity, β-cell function, body fat distribution, skeletal muscle and adipose tissue biology, cardiovascular function, cardiorespiratory fitness, muscular strength, immune function, and the gut microbiome.

Detailed Description

Reduced energy intake and increased physical activity have profound effects on cardiometabolic health as assessed by insulin sensitivity, β-cell function, serum lipids, intra-abdominal fat mass, intrahepatic triglyceride content, and blood pressure, and is the cornerstone of treatment for people with obesity. However, the specific additional therapeutic effects of regular exercise in conjunction with diet-induced weight loss are not clear. In addition, the optimal dietary macronutrient composition needed to reduce cardiometabolic risk is not known. The use of a very low fat, plant-forward diet is becoming increasingly popular to treat people with obesity and is the only diet therapy that is reimbursed by Medicare in the treatment of people with coronary heart disease.

Participants will undergo nutritional counseling and have supervised exercise training 4 days per week plus unsupervised exercise sessions performed 2 days per week until 7-10% weight loss is achieved. Meals will be provided and food diaries will be kept during weight loss. Tests before and after the intervention will include muscular strength and aerobic fitness, cardiovascular assessments, glucose tolerance tests, hyperinsulinemic euglycemic clamp test for insulin sensitivity, muscle biopsies, body composition scans, blood tests, and urine and stool collections.

The overarching goal of this project is to conduct a comprehensive characterization of weight loss induced by using a PB diet with regular exercise in people with obesity, prediabetes and insulin resistance, followed by a comparison of the effects of this study with those from another study that is evaluating the effect of the same amount of weight loss induced by using a PB diet alone, without exercise. Specifically, we will evaluate changes in body composition, body fat distribution, cardiopulmonary function, muscle strength, the plasma proteome, insulin sensitivity, beta-cell function, systemic inflammation, muscle cellular metabolic pathways, and the gut microbiome to determine cellular, multiorgan, and whole-body effects of PB diet alone and PB diet plus exercise. Accordingly, this study will fill two important gaps in our knowledge that have considerable physiological and clinical significance; the data from this study will provide: 1) a better understanding of the effects of calorie restriction-induced weight loss plus exercise on a series of key outcome measures, and 2) the potential additional benefit of adding regular exercise to a plant-forward diet.

Conditions

Obesity; Insulin Resistance

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Weight loss with diet with exercise

Persons with obesity with blood glucose concentrations higher than recommended and a moderate to high amount of fat in the liver (people with metabolically abnormal obesity) will be tested before and after \~7-10% weight loss. Following baseline testing, participants will be placed on a caloric-restricted plant-based very-low-fat (PB) diet and an exercise program until \~7-10% weight loss is achieved; they will then be re-tested so that pre- and post-intervention outcomes can be compared.

Group Type: EXPERIMENTAL

Weight loss with very low fat plant-based diet and regular exercise

Intervention Type: OTHER

Participants will lose \~7-10% of their body weight while on a calorie-restricted very low fat plant-based (PB) diet and performing exercise 6 days/week (4 sessions/week under direct supervision). The macronutrient composition of the diet is approximately 70% of energy from carbohydrate, 15% from protein, and 15% from fat. Food will be provided in the form of take-out meals and will be picked up by participants during weekly study visits with a weight management dietitian. To promote adherence to the diet and exercise intervention, subjects will participate in a lifestyle intervention program that includes dietary and behavioral education topics. Treatment will be provided in weekly individual or group sessions depending on subject availability. (Note: this is the only intervention for the study; the hyperinsulinemic euglycemic clamp is not an intervention but is the gold standard for evaluating insulin sensitivity, a primary study outcome.)

Interventions

Weight loss with very low fat plant-based diet and regular exercise

Participants will lose \~7-10% of their body weight while on a calorie-restricted very low fat plant-based (PB) diet and performing exercise 6 days/week (4 sessions/week under direct supervision). The macronutrient composition of the diet is approximately 70% of energy from carbohydrate, 15% from protein, and 15% from fat. Food will be provided in the form of take-out meals and will be picked up by participants during weekly study visits with a weight management dietitian. To promote adherence to the diet and exercise intervention, subjects will participate in a lifestyle intervention program that includes dietary and behavioral education topics. Treatment will be provided in weekly individual or group sessions depending on subject availability. (Note: this is the only intervention for the study; the hyperinsulinemic euglycemic clamp is not an intervention but is the gold standard for evaluating insulin sensitivity, a primary study outcome.)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥18 and ≤55 years
• BMI ≥30.0 and ≤50.0 kg/m²
• HbA1c ≥5.7%, or fasting plasma glucose concentration ≥100 mg/dl, or 2-hr OGTT plasma glucose concentration ≥140 mg/dl

Exclusion Criteria

• Medical, surgical, or biological menopause
• Previous bariatric surgery
• Structured exercise >2 days/week for ≥35 minutes of intense exercise (e.g., jogging, activity that causes heavy breathing and sweating) or ≥150 min per week of structured exercise (e.g., brisk walking)
• Unstable weight (>4% change during the last 2 months before entering the study)
• Significant organ system dysfunction (e.g., diabetes requiring medications, severe pulmonary, kidney or cardiovascular disease)
• Cancer or cancer that has been in remission for <5 years
• Polycystic ovary syndrome
• Major psychiatric illness
• Conditions that render subject unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders)
• Use of medications that are known to affect the study outcome measures (e.g., steroids, non-statin lipid lowering medications) or increase the risk of study procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this study
• Use of antibiotics in last 60 days
• Smoke cigarettes, use marijuana >2 x/week, or use of illegal drugs
• Men who consume >21 units (e.g. glass of wine or bottle of beer) of alcohol per week and women who consume >14 units of alcohol per week
• Pregnant or lactating women
• Vegans, vegetarians, those with lactose intolerance and/or severe aversions/sensitivities to eggs, fish, nuts, wheat and soy, and/or any individuals with food allergies that induce an anaphylactic response
• Persons who are not able to grant voluntary informed consent
• Persons who are unable or unwilling to follow the study protocol or who, for any reason, the research team considers not an appropriate candidate for this study, including non-compliance with screening appointments or study visits

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Foundation for Barnes-Jewish Hospital

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samuel Klein, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University in St. Louis School of Medicine

St Louis, Missouri, United States

Countries

United States

References

Beals JW, Kayser BD, Smith GI, Schweitzer GG, Kirbach K, Kearney ML, Yoshino J, Rahman G, Knight R, Patterson BW, Klein S. Dietary weight loss-induced improvements in metabolic function are enhanced by exercise in people with obesity and prediabetes. Nat Metab. 2023 Jul;5(7):1221-1235. doi: 10.1038/s42255-023-00829-4. Epub 2023 Jun 26.

Reference Type: DERIVED

PMID: 37365374 (View on PubMed)

Other Identifiers

201512088

Identifier Type: -

Identifier Source: org_study_id