- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02452567
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
Withdrawn
Conditions
Intervention / Treatment
Study Type
Interventional
Phase
- 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
-
-
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
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 |
Intervention / Treatment |
---|---|
Experimental: Metabolically abnormal lean
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
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
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.
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)
May 1, 2015
Primary Completion (Actual)
May 1, 2021
Study Completion (Actual)
May 1, 2021
Study Registration Dates
First Submitted
April 15, 2015
First Submitted That Met QC Criteria
May 19, 2015
First Posted (Estimate)
May 22, 2015
Study Record Updates
Last Update Posted (Actual)
May 28, 2021
Last Update Submitted That Met QC Criteria
May 25, 2021
Last Verified
May 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201501010
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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