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

May 25, 2021 updated by: Washington University School of Medicine
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
An average of 6-8 months from baseline testing to 8-10% weight loss

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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)
Time Frame: An average of 6-8 months from baseline testing to 8-10% weight loss
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.
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
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.
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
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
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
An average of 6-8 months from baseline testing to 8-10% 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
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
An average of 6-8 months from baseline testing to 8-10% weight loss
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).
An average of 6-8 months from baseline testing to 8-10% weight loss

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 22, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 28, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 25, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201501010

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