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

Primary Purpose

Weight Loss

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

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

About this trial

This is an interventional other trial for Weight Loss

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Metabolically abnormal lean

Arm Description

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

Outcomes

Primary Outcome Measures

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

Evaluate insulin sensitivity through the hyperinsulinemic-euglycemic clamp procedure.

Secondary Outcome Measures

Change in Beta-Cell function

Administer 3 hour oral glucose tolerance test before and after weight loss to determine the effects of weight loss on beta cell function

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

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

Inta-abdominal adipose tissue volume will be assessed before and after weight loss to determine the effects of weight loss

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

Blood will be drawn for the complete metabolic panel and lipid panel before and after 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

Plasma samples and adipose tissue biopsies will be obtained during the hyperinsulinemic-euglycemic clamp procedure before and after weight loss

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

Muscle and adipose tissue biopsy samples will be obtained during the hyperinsulinemic-euglycemic clamp procedure before and after weight loss

Modification of gut microbiota

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).

Full Information

NCT ID

NCT02452567

First Posted

April 15, 2015

Last Updated

May 25, 2021

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT02452567

Brief Title

Effect of Moderate Weight Loss in Metabolically Abnormal Lean Subjects

Acronym

MAL

Official Title

Effect of Moderate Weight Loss in Metabolically Abnormal Lean Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Withdrawn

Why Stopped

Difficulty recruiting participants that met the inclusion criteria

Study Start Date

May 2015 (Actual)

Primary Completion Date

May 2021 (Actual)

Study Completion Date

May 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Weight Loss

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metabolically abnormal lean

Arm Type

Experimental

Arm Description

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

Intervention Type

Other

Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Evaluate insulin sensitivity through the hyperinsulinemic-euglycemic clamp procedure.

Time Frame

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

Secondary Outcome Measure Information:

Title

Change in Beta-Cell function

Description

Administer 3 hour oral glucose tolerance test before and after weight loss to determine the effects of weight loss on beta cell function

Time Frame

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

Title

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

Title

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

Description

Inta-abdominal adipose tissue volume will be assessed before and after weight loss to determine the effects of weight loss

Time Frame

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

Title

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

Description

Blood will be drawn for the complete metabolic panel and lipid panel before and after weight loss

Time Frame

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

Title

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

Description

Plasma samples and adipose tissue biopsies will be obtained during the hyperinsulinemic-euglycemic clamp procedure before and after weight loss

Time Frame

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

Title

Description

Muscle and adipose tissue biopsy samples will be obtained during the hyperinsulinemic-euglycemic clamp procedure before and after weight loss

Time Frame

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

Title

Modification of gut microbiota

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Samuel Klein, MD

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

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Effect of Moderate Weight Loss in Metabolically Abnormal Lean Subjects

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