Clinical trial NCT02452567: Effect of Moderate Weight Loss in Metabolically Abnormal Lean Subjects
Official title: Effect of Moderate Weight Loss in Metabolically Abnormal Lean Subjects
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Weight Loss
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2015-05-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility 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

Primary outcomes:
measure: Change in insulin sensitivity as assessed by the hyperinsulinemic-euglycemic clamp technique
timeFrame: An average of 6-8 months from baseline testing to 8-10% weight loss
Secondary outcomes:
measure: Change in Beta-Cell function
timeFrame: An average of 6-8 months from baseline testing to 8-10% weight loss
measure: Change in fat mass and fat free mass as assessed by dual-energy x-ray absorptiometry (DXA)
timeFrame: An average of 6-8 months from baseline testing to 8-10% weight loss
measure: Change in intra-abdominal adipose tissue volume as assessed by magnetic resonance imagining.
timeFrame: An average of 6-8 months from baseline testing to 8-10% weight loss
measure: Change in plasma lipid profile as assessed by the complete metabolic panel and lipid panel.
timeFrame: An average of 6-8 months from baseline testing to 8-10% weight loss
measure: 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
timeFrame: An average of 6-8 months from baseline testing to 8-10% weight loss
measure: 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
timeFrame: An average of 6-8 months from baseline testing to 8-10% weight loss
measure: Modification of gut microbiota
timeFrame: An average of 6-8 months from baseline testing to 8-10% weight loss
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Samuel Klein, MD
role: PRINCIPAL_INVESTIGATOR
References: