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Effect of Weight Loss on Body Composition and Metabolic Function in Women With Lipedema

Not Applicable
Active, not recruiting
Conditions
Lipedema
Metabolism
Interventions
Dietary Supplement: Weight loss
Registration Number
NCT03271034
Lead Sponsor
Washington University School of Medicine
Brief Summary

Lipedema is a disorder characterized by massive, bilateral accumulation of fat below the waist and in the legs. Enlargement of the lower extremities is often accompanied by leg pain and accumulation of fluid. Little is known about the functional changes that lead to fat accumulation and pain in women with lipedema. The goals of this project are to conduct a comprehensive characterization of abdominal and femoral fat tissues in lean and obese women with lipedema and to evaluate the potential effect of diet-induced weight loss as a therapy.

Once enrolled in the study, the following tests will be conducted on lean women with lipedema: characterization of body composition (fat tissue distribution), insulin sensitivity (response to insulin) and adipose tissue biology. The following tests will be conducted on obese women with lipedema: characterization of body composition (fat tissue distribution), insulin sensitivity (response to insulin), adipose tissue biology, and immune system function/inflammation. As control, we will have BMI-matched women that are metabolically normal lean (MNL), metabolically normal obese (MNO) and metabolically abnormal obese (MAO) already analyzed in different studies at Washington University (IRB# 201512086). MNL, MAO and MNO subjects underwent the same testing described above for the lipedema. Therefore, we will use the data generated from IRB# 201512086 as comparison groups in the statistical analysis to understand differences and similarities between lipedema and obesity.

A second aim of the study is to determine the effect of diet-induced weight loss on body composition, insulin sensitivity, and adipose tissue biology in women with lipedema. The results from this second aim of the study will hopefully provide important insights on the efficacy of diet therapy in managing lipedema.

Detailed Description

Once informed consent has been obtained, participants will complete 1 screening visit.

The screening visit includes a medical history, physical examination, pregnancy test (for women of childbearing potential), blood tests, urine drug test, an oral glucose tolerance test, resting electrocardiogram (ECG), and questionnaires.

Baseline testing will be performed in 2 visits requiring 1 inpatient overnight stay and will require approximately 30 hours in total to complete testing. Testing will include imaging scans to determine thigh fat mass; abdominal (belly) fat mass and liver fat content; DXA scan to assess whole-body and leg fat mass; blood samples; hyperinsulinemic-euglycemic clamp procedure; immune system function/inflammation (performed exclusively in people with obesity and lipedema and BMI-matched controls); and adipose tissue (fat) biopsies.

Once Baseline Testing is completed, participants will start 5-10% dietitian and/or behaviorist guided weight-loss for about 4 to 6 months.

Participant will keep a food diary and have weekly visits (in person or remote) with a study dietitian and/or behaviorist.

After weight loss, the testing completed during baseline will be repeated.

Study procedures:

1. Medical history \& physical exam

2. Urine drug/pregnancy Test

3. Blood pressure, pulse, height, weight

4. Electrocardiogram (ECG)

5. Blood tests for routine lab analyses

6. Oral glucose tolerance test (OGTT)

7. Screening Questionnaires

8. Dual energy X-ray absorptiometry (DXA) scan to assess whole-body and leg fat mass

9. Magnetic Resonance Imaging (MRI) for Body Composition to determine the amount of fat in the liver, abdomen (belly), and thigh.

10. Metabolism study (hyperinsulinemic-euglycemic clamp procedure) to assess how well insulin works to control blood glucose (sugar) concentrations.

11. Abdominal (belly) and thigh fat biopsies

12. Immune function (performed in obese with lipedema subjects and BMI-matched controls).

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Female
Target Recruitment
20
Inclusion Criteria
  • Diagnosis of Lipedema
  • Lean women with lipedema (BMI >19.5 kg/m² and <26.0 kg/m²)
  • Women with obesity and lipedema (BMI >30.0 kg/m² and <50.0 kg/m²)
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Exclusion Criteria
  • Medical, surgical or biological menopause
  • Previous bariatric surgery
  • Diagnosis of Type 2 Diabetes
  • HbA1C <5.7%
  • Structured exercise >2 days/week for ≥35 minutes of intense exercise (e.g., jogging, activity that cause heavy breathing and sweating) or ≥150 minutes per week of structured exercise (e.g., brisk walking)
  • Unstable weight (>4% change in weight during the last 2 months before entering the study)
  • Significant organ system dysfunction (e.g., diabetes, severe pulmonary, kidney or cardiovascular disease)
  • Cancer or cancer that has been in remission for <5 years
  • Polycystic Ovary Syndrome
  • Major psychiatric illness
  • Conditions that render participant unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders)
  • Use of medications that are known to affect the study outcome measures (e.g., steroids, non-statin lipid-lowering medications) or increase the risk of study procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this study
  • Smoke cigarettes >10 cigarettes/week
  • Consume >14 units of alcohol per week
  • Pregnant or lactating women
  • Persons who are not able to grant voluntary informed consent
  • Persons who are unable or unwilling to follow the study protocol or who, for any reason, the research team considers not an appropriate candidate for this study, including non-compliance with screening appointments or study visits.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Lean women with LipedemaWeight lossBody composition, adipose tissue biology, insulin sensitivity assessed before and after low-calorie diet therapy to achieve 5-10% weight loss.
Women with Obesity and LipedemaWeight lossBody composition, adipose tissue biology, insulin sensitivity and immune function/inflammation assessed before and after low-calorie diet therapy to achieve 5-10% weight loss.
Primary Outcome Measures
NameTimeMethod
Change in thigh subcutaneous adipose tissue volumeBefore and after 5-10% weight loss (3-4 months)

Thigh subcutaneous adipose tissue volume assessed by magnetic resonance imaging.

Whole-body insulin sensitivityBaseline testing

Whole-body insulin sensitivity determined by using the hyperinsulinemic-euglycemic clamp procedure between women with obesity and women with obesity and lipedema.

Secondary Outcome Measures
NameTimeMethod
Thigh subcutaneous adipose tissue volumeBaseline testing

Thigh subcutaneous adipose tissue volume assessed by magnetic resonance imaging in women with obesity and lipedema, women with obesity and lean women.

Change in whole-body insulin sensitivityBefore and after 5-10% weight loss (3-4 months)

Whole-body insulin sensitivity determined by using the hyperinsulinemic-euglycemic clamp procedure.

Leg fat massBaseline testing

Leg fat mass will be assessed by dual-energy x-ray absorptiometry (DXA) in women with obesity and lipedema, women with obesity and lean women.

Change in leg fat massBefore and after 5-10% weight loss (3-4 months)

Leg fat mass will be assessed by dual-energy x-ray absorptiometry (DXA).

Adipose tissue immune cellsBaseline testing

Immune cell numbers in upper and lower body subcutaneous adipose tissue stromal vascular fraction content assessed by flow cytometry in women with obesity and lipedema only.

Change in adipose tissue immune cellsBefore and after 5-10% weight loss (3-4 months)

Immune cell numbers in upper and lower body subcutaneous adipose tissue stromal vascular fraction content assessed by flow cytometry.

Trial Locations

Locations (1)

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

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