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

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ClinicalTrials.gov Identifier: NCT02706288
Recruitment Status : Recruiting
First Posted : March 11, 2016
Last Update Posted : September 12, 2018
Sponsor:
Collaborator:
Barnes-Jewish Hospital
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Obesity Insulin Resistance Other: Weight loss with very low fat plant-based diet and regular exercise Not Applicable

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-based (PB) 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 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, heavy water metabolism, resting energy expenditure/metabolic rate, muscle and fat biopsies, body composition scans, blood tests, and urine and stool collection.

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 MAO, 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 metabolome, insulin sensitivity, beta-cell function, systemic and adipose tissue inflammation and immune system function, adipose tissue and 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 a PB diet plus exercise on a series of key outcome measures, and 2) the potential additional benefit of adding regular exercise to a PB diet.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: The Effects of a Calorie Restricted, Very Low Fat Plant-based Diet and Multi-component Exercise Program on Metabolic Health in Metabolically Abnormal Obese Adults
Actual Study Start Date : March 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Other: 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.)




Primary Outcome Measures :
  1. Change in insulin sensitivity [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Liver and skeletal muscle insulin sensitivity will be assessed by hyperinsulinemic euglycemic clamp technique, before and after weight loss.

  2. Change in gut microbiome [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Gut microbiota (bacterial RNA sequencing to determine what proteins can be made by the microbiota) and the meta-metabolome (metabolites made by the microbiota) will be assessed before and after weight loss.

  3. Change in beta-cell function [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Beta-cell function will be assessed from a modified oral glucose tolerance test before and after weight loss.

  4. Change in plasma lipid profile [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    The plasma lipid profile will be assessed from a fasting blood sample before and after weight loss.


Secondary Outcome Measures :
  1. Change in aerobic fitness [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Maximal oxygen consumption will be assessed using indirect calorimetry during a graded exercise test to volitional fatigue, before and after weight loss.

  2. Change in muscular strength [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Muscle strength will be evaluated as the maximal amount of weight the participant is able to lift for one repetition (1 RM) for the following exercises: leg press, seated row, knee flexion, and chest press, before and after weight loss.

  3. Change in fat mass and fat free mass [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA) before and after weight loss.

  4. Change in intra-abdominal adipose tissue volume and thigh muscle volume [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Intra-abdominal adipose tissue and thigh muscle volume will be assessed by magnetic resonance imagining (MRI) before and after weight loss.

  5. Change in intra-hepatic triglyceride content [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Intra-hepatic triglyceride content will be assessed by magnetic resonance spectroscopy (MRS) before and after weight loss.

  6. Change in carotid artery intima media thickness [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Carotid artery intima media thickness will be assessed by ultrasound imaging before and after weight loss.

  7. Change in fasting plasma glucose [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Fasting plasma glucose concentrations will be evaluated from a fasting blood sample before and after weight loss.

  8. Change in glycosylated hemoglobin (HbA1c) [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    HbA1c will be evaluated from a fasting blood sample before and after weight loss.

  9. Change in 24 hour glucose concentrations with feeding [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Glucose concentrations will be evaluated from frequent blood samples over a 24 h period, before and after weight loss, with the participant consuming mixed meals throughout the day.

  10. Changes in metabolic pathways in adipose tissue and skeletal muscle tissue [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Metabolic pathways in adipose tissue and vastus lateralis from tissue biopsies will be evaluated before and after weight loss.

  11. Changes in physical activity [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Physical activity will be assessed using tri-axial accelerometry before and after weight loss.

  12. Changes in sleep [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Sleep will be assessed using tri-axial accelerometry validated for assessment of sleep efficiency, before and after weight loss.

  13. Changes in body weight [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Body weight will be measured before and after weight loss.

  14. Changes in body mass index [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Body mass index will be calculated from weight and height before and after weight loss.

  15. Changes in endothelial function assessed by reactive hyperemia [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Endothelial function will be assessed non-invasively, before and after weight loss, by the reactive hyperemic index (RHI) which represents the ratio of peripheral arterial tone (PAT) amplitude in the test arm to control arm measured between 60 s and 120 s following occlusion of the forearm by a blood pressure cuff.

  16. Changes in cardiac structure [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Cardiac imaging will be performed before and after weight loss for determination of changes in heart structure.

  17. Change in muscle proteins involved in the regulation of glucose metabolism [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Muscle biopsy samples will be obtained before and after weight loss and analyzed for proteins involved in regulating glucose metabolism.

  18. Change in adipose tissue proteins involved in the regulation of glucose metabolism [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Adipose tissue biopsy samples will be obtained before and after weight loss and analyzed for proteins involved in regulating glucose metabolism.

  19. Change in adipose tissue proteins involved in the regulation of immune function [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Adipose tissue biopsy samples will be obtained before and after weight loss and analyzed for proteins involved in regulating immune function.

  20. Change in muscle proteins involved in the regulation of inflammation [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Muscle biopsy samples will be obtained before and after weight loss and analyzed for proteins involved in regulating inflammation.

  21. Change in adipose tissue proteins involved in the regulation of inflammation [ Time Frame: An average of 6 months from baseline testing to 7-10% weight loss ]
    Adipose tissue biopsy samples will be obtained before and after weight loss and analyzed for proteins involved in regulating inflammation.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age ≥18 and ≤55 years
  • BMI ≥30.0 and ≤50.0 kg/m²
  • IHTG content ≥5.6%; HbA1c ≥5.7%, or fasting plasma glucose concentration ≥100 mg/dl, or 2-hr OGTT plasma glucose concentration ≥140 mg/dl OR HbA1c ≥5.8% and 2-hr OGTT plasma glucose concentration ≥150 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02706288


Contacts
Contact: George G Schweitzer, PhD 314-362-4884 george.schweitzer@wustl.edu
Contact: Heather Gentile 314-273-1879 hgentile@wustl.edu

Locations
United States, Missouri
Washington University in St. Louis School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: George Schweitzer, PhD    314-362-4884    george.schweitzer@wustl.edu   
Sponsors and Collaborators
Washington University School of Medicine
Barnes-Jewish Hospital
Investigators
Principal Investigator: Samuel Klein, MD Washington University School of Medicine

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02706288     History of Changes
Other Study ID Numbers: 201512088
First Posted: March 11, 2016    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: All of the data from individual subjects will be maintained confidentially and their names and identities will not be disclosed in any published document.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases