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Effect of Moderate Weight Loss in Metabolically Abnormal Lean Subjects (MAL)

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ClinicalTrials.gov Identifier: NCT02452567
Recruitment Status : Withdrawn (Difficulty recruiting participants that met the inclusion criteria)
First Posted : May 22, 2015
Last Update Posted : May 28, 2021
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
Obesity is associated with a constellation of cardiometabolic abnormalities (including insulin resistance, elevated blood pressure and dyslipidemia) that are risk factors for diabetes and cardiovascular disease. Weight loss can improve all of the cardiometabolic abnormalities associated with obesity. Up to ~25% of lean people (Body Mass Index [BMI] 18.5-24.9 kg/m²) have many of the cardiometabolic abnormalities associated with obesity and are referred to as metabolically abnormal lean (MAL) people. However, the MAL phenotype is not well characterized, and it is unclear whether weight loss has beneficial metabolic effects in already lean people. Accordingly, the goal of this study is to: 1) carefully phenotype MAL people and 2) evaluate the effect of moderate (8-10%) diet-induced weight loss in MAL people. This will be investigated in 15 MAL (defined as having 2 or more of the following: intrahepatic triglyceride (IHTG) content ≥5.6%, glycated hemoglobin ≥5.7%, fasting plasma glucose concentration ≥100 mg/dl, 2-hr oral glucose tolerance test (OGTT) plasma glucose concentration ≥140 mg/dl, homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.5) men and women. Only lean people who have a BMI ≥21.0 but <25.0 kg/m² will be asked to lose weight to avoid the risk that participants become underweight (BMI <18.5 kg/m²) during weight loss therapy.

Condition or disease Intervention/treatment Phase
Weight Loss Other: Moderate (8-10%) diet-induced weight loss Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Effect of Moderate Weight Loss in Metabolically Abnormal Lean Subjects
Actual Study Start Date : May 2015
Actual Primary Completion Date : May 2021
Actual Study Completion Date : May 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Metabolically abnormal lean
Moderate (8-10%) diet-induced weight loss.
Other: Moderate (8-10%) diet-induced weight loss
MAL participants will meet with the study dietitian to lose ~8-10% of their body weight through diet-intervention.




Primary Outcome Measures :
  1. Change in insulin sensitivity as assessed by the hyperinsulinemic-euglycemic clamp technique [ Time Frame: An average of 6-8 months from baseline testing to 8-10% weight loss ]
    Evaluate insulin sensitivity through the hyperinsulinemic-euglycemic clamp procedure.


Secondary Outcome Measures :
  1. Change in Beta-Cell function [ Time Frame: An average of 6-8 months from baseline testing to 8-10% weight loss ]
    Administer 3 hour oral glucose tolerance test before and after weight loss to determine the effects of weight loss on beta cell function

  2. Change in fat mass and fat free mass as assessed by dual-energy x-ray absorptiometry (DXA) [ Time Frame: An average of 6-8 months from baseline testing to 8-10% weight loss ]
  3. Change in intra-abdominal adipose tissue volume as assessed by magnetic resonance imagining. [ Time Frame: An average of 6-8 months from baseline testing to 8-10% weight loss ]
    Inta-abdominal adipose tissue volume will be assessed before and after weight loss to determine the effects of weight loss

  4. Change in plasma lipid profile as assessed by the complete metabolic panel and lipid panel. [ Time Frame: An average of 6-8 months from baseline testing to 8-10% weight loss ]
    Blood will be drawn for the complete metabolic panel and lipid panel before and after weight loss

  5. Change in markers of inflammation in plasma and adipose tissue as assessed from samples obtained during the hyperinsulinemic-euglycemic clamp procedure with adipose tissue biopsies [ Time Frame: An average of 6-8 months from baseline testing to 8-10% weight loss ]
    Plasma samples and adipose tissue biopsies will be obtained during the hyperinsulinemic-euglycemic clamp procedure before and after weight loss

  6. Change in cellular factors involved in mediating insulin action in muscle and adipose tissue as assessed by muscle and adipose tissue biopsies obtained during the hyperinsulinemic-euglycemic clamp procedure [ Time Frame: An average of 6-8 months from baseline testing to 8-10% weight loss ]
    Muscle and adipose tissue biopsy samples will be obtained during the hyperinsulinemic-euglycemic clamp procedure before and after weight loss

  7. Modification of gut microbiota [ Time Frame: An average of 6-8 months from baseline testing to 8-10% weight loss ]
    Monthly stool collection will be used to assess the composition of the gut microbiota, meta-transcriptome (bacterial RNA sequencing to determine what proteins can be made by the microbiota), and the meta-metabolome (metabolites made by the microbiota).



Information from the National Library of Medicine

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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:

  • BMI 21.0-24.9 kg/m²
  • Weight stable (+/- 2% for at least 3 months before enrollment)
  • Two or more of the following: IHTG content ≥5.6%, HOMA- IR index ≥ 2.5, HbA1C ≥ 5.7%, 2-hr OGTT plasma glucose concentration ≥ 140 mg/dl, fasting plasma glucose concentration ≥ 100 mg/dl.

Exclusion Criteria:

  • Women who are pregnant or breastfeeding
  • Evidence of significant organ system dysfunction or disease (e.g., diabetes, chronic kidney disease, advanced heart disease, etc.)
  • 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
  • Use of dietary supplements or medications known to affect metabolism
  • Eating disorder (assessed by using the Eating Disorder Examination Questionnaire [EDE-Q])
  • Participation in structured endurance or resistance exercise program >150 min/week
  • Use of tobacco products
  • Unable or unwilling to follow the study protocol or the research team believes that for any reason the volunteer is not an appropriate candidate for this study, including non-compliance with screening appointments or previous appointments/contact arrangements
  • Individuals that take Coumadin or similar anticoagulants
  • Use of antibiotics in last 60 days
  • Previous bariatric surgery
  • Cancer or cancer that has been in remission for <5 years
  • Major psychiatric illness

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): NCT02452567


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Samuel Klein, MD Washington University School of Medicine
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02452567    
Other Study ID Numbers: 201501010
First Posted: May 22, 2015    Key Record Dates
Last Update Posted: May 28, 2021
Last Verified: May 2021
Additional relevant MeSH terms:
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Body Weight
Weight Loss
Body Weight Changes