Effect of Moderate Weight Loss in Metabolically Abnormal Lean Subjects

NCT02452567 | Withdrawn DMC

• 1 other identifier: 201501010
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Weight Loss

Outcome Measures

Primary Outcomes (1)

• Change in insulin sensitivity as assessed by the hyperinsulinemic-euglycemic clamp technique

  Evaluate insulin sensitivity through the hyperinsulinemic-euglycemic clamp procedure.

  An average of 6-8 months from baseline testing to 8-10% weight loss

Secondary Outcomes (7)

• Change in Beta-Cell function

  An average of 6-8 months from baseline testing to 8-10% weight loss

• Change in fat mass and fat free mass as assessed by dual-energy x-ray absorptiometry (DXA)

  An average of 6-8 months from baseline testing to 8-10% weight loss

• Change in intra-abdominal adipose tissue volume as assessed by magnetic resonance imagining.

  An average of 6-8 months from baseline testing to 8-10% weight loss

• Change in plasma lipid profile as assessed by the complete metabolic panel and lipid panel.

  An average of 6-8 months from baseline testing to 8-10% weight loss

• 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

  An average of 6-8 months from baseline testing to 8-10% weight loss

Study Arms (1)

Metabolically abnormal lean

EXPERIMENTAL

Moderate (8-10%) diet-induced weight loss.

Other: Moderate (8-10%) diet-induced weight loss

Interventions

Moderate (8-10%) diet-induced weight loss OTHER

MAL participants will meet with the study dietitian to lose \~8-10% of their body weight through diet-intervention.

Metabolically abnormal lean

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Weight Loss

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Samuel Klein, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: May 22, 2015
• Study Start: May 1, 2015
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: May 28, 2021

Record last verified: 2021-05

Locations

US (1)