Insight Into Subcutaneous Adipose Tissue Disorders (INSIGHT)

• ClinicalTrials.gov Identifier: NCT02838277
• Recruitment Status: Unknown
• First Posted: July 20, 2016
• Last Update Posted: September 15, 2017
• Sponsor: University of Arizona
• Collaborator: Lipedema Foundation
• Information provided by (Responsible Party): KHerbst, University of Arizona

Study Description

Brief Summary:

The INSIGHT study aims to phenotype individuals with subcutaneous adipose tissue (SAT) disorders specifically lipedema and Dercum's disease with an aim to find a cure for the SAT in these disorders that is resistant to diet and exercise.

Condition or disease
Lipedema; Dercum's Disease; Familial Multiple Lipomatosis; Madelung's Disease

Detailed Description:

Lipedema is a syndrome of painful fatty enlargement of the buttocks, hips and thighs primarily in women which cannot be lost by diet, exercise or bariatric surgery. Arms are affected in 80% of women with lipedema to varying degrees. The etiology of lipedema is not known and there are no evidence-based treatments that work for a majority of individuals except for excision of the subcutaneous adipose tissue (SAT) by liposuction which has risks. Millions of women are affected with lipedema yet they are grossly under-diagnosed, have mobility issues and can develop lymphedema. The goal of this project is to better understand the etiology of lipedema SAT, find out how it is different from non-lipedema SAT, to improve our ability to identify the abnormal SAT and determine the response of the tissue to therapeutics by imaging and biomarkers. People with diffuse Dercum's disease (DD) appear to have lipedema plus a tissue inflammation that causes illness and pain. People with SAT disorders that have similarities to lipedema will also be included in this protocol. More research is needed to determine how these fatty disorders are similar and different from each other and from obesity so they can be distinguished clinically and by laboratory testing and imaging. Since these painful fatty disorders are associated with SAT growth, research focused on these disorders may provide unique insight into mechanisms of obesity.

Study Design

• Study Type: Observational
• Estimated Enrollment: 500 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Insight Into Subcutaneous Adipose Tissue Disorders As Part of The TREAT Program (Treatment, Research, Education, Adipose Tissue) at the University of Arizona
• Study Start Date: June 2016
• Estimated Primary Completion Date: June 2018
• Estimated Study Completion Date: December 2018

Groups and Cohorts

Group/Cohort
Lipedema; Women with all stages of lipedema
Dercum's disease; Men and women with nodular, mixed and diffuse Dercum's disease
Control; Sex, age and BMI matched controls.
Familial Multiple Lipomatosis; Women and men with multiple lipomas and/or angiolipomas
Madelung's disease; Men and women with different types of Madelung's disease.

Outcome Measures

Primary Outcome Measures :

1. Transcriptomics of all enrolled subjects from a single timepoint to assess for changes in gene expression in lipedema tissue compared to controls [ Time Frame: Single time point study with imaging, blood draw, exam and biopsies over multiple days for a total of approximately 8 hours time. ]
   This is a phenotyping study that collects data as a single time point though studies may occur on different days.
2. Metabolomics of all enrolled subjects from a single timepoint to assess for changes in metabolites in lipedema tissue compared to controls [ Time Frame: Single time point study with imaging, blood draw, exam and biopsies over multiple days for a total of approximately 8 hours time. ]
   This is a phenotyping study that collects data as a single time point though studies may occur on different days.
3. Lipidomics of all enrolled subjects from a single timepoint to assess for changes in lipid particles in lipedema tissue and blood compared to controls [ Time Frame: Single time point study with imaging, blood draw, exam and biopsies over multiple days for a total of approximately 8 hours time. ]
   This is a phenotyping study that collects data as a single time point though studies may occur on different days.
4. Cytokines of all enrolled subjects from a single timepoint to assess for changes in cytokine arrays in lipedema tissue and blood compared to controls [ Time Frame: Single time point study with imaging, blood draw, exam and biopsies over multiple days for a total of approximately 8 hours time. ]
   This is a phenotyping study that collects data as a single time point though studies may occur on different days.
5. Myostatin of all enrolled subjects from a single timepoint to assess for levels of myostatin in lipedema tissue and blood compared to controls [ Time Frame: Single time point study with imaging, blood draw, exam and biopsies over multiple days for a total of approximately 8 hours time. ]
   This is a phenotyping study that collects data as a single time point though studies may occur on different days.

Biospecimen Retention:   Samples With DNA

Blood, adipose tissue and DNA

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Men and women with lipedema and Dercum's disease and controls.

Criteria

Inclusion Criteria:

1. Ambulatory males and/or females of any race able to understand the consent process.
2. 19-70 years of age.
3. Diagnosis of lipedema, Dercum's disease or familial multiple lipomatosis or other similar fat disorder.
4. Individuals without a fat disorder (will be matched by age, sex, race and body mass index to individuals in "2").
5. Weight stable for past three months within a 10 pound range per personal report of the subject.
6. Overweight or obese (BMI > 26 kg/m2) in order to be able to get enough SAT for the biopsy.
7. Individuals with BMI < 26 kg/m2 may participate in all aspects of the study protocol except the SAT biopsy.
8. Thyroid levels in the normal range as confirmed by a TSH level. May have treated hypothyroidism that is stable over 6 months.

Exclusion Criteria:

1. HIV infection (because of the associated lipodystrophy and fatty growths [lipomas]).
2. Subjects will be excluded from having a SAT biopsy with any history of scleroderma, keloid formation or other skin condition that would result in substantial scarring after biopsy, a history of recurrent cellulitis, any history of bleeding diathesis that would place the subject at great risk for persistent bleeding after a biopsy/liposuction, any history of major complication after a previous biopsy including requirement of a blood transfusion, hospitalization, failure to heal, or major infection, requiring intravenous antibiotics, or anyone whose skin and tissue would put them at risk for an infection after the biopsy per the assessment of study staff and the principal investigator. These individuals may participate in the remainder of the protocol, just not the SAT biopsy.
3. Use of any immunosuppressant or corticosteroid medication.
4. Use of any anti-inflammatory medication such as NSAIDs, aspirin, histamine (H) 1 blocker, H2 blocker, tetracycline or corticosteroids within five days of the study procedure visit.
5. Use of medications that might cause weight gain (e.g., second generation anti-psychotics).
6. Blood donation less than 56 days prior to screening visit.
7. Tobacco or marijuana use which may alter inflammation in the body.
8. Any antibiotics within the last month.
9. Barium enema in the last week which would affect gut bacteria and the MRI.
10. Pregnancy due to the risks associated with the fat biopsy in the area of the fetus and because pregnancy will alter hormone levels.

Contacts and Locations

Contacts

Contact: Karen L Herbst, PhD, MD; 5206267689; karenherbst@deptofmed.arizona.edu

Contact: Christopher Ussery, MS; 5206267689; cussery@email.arizona.edu

Locations

United States, Arizona

University of Arizona College of Medicine (South Campus); Recruiting

Tucson, Arizona, United States, 85714

Contact: Christopher L Ussery, MS 520-626-7689 treatprogram@deptofmed.arizona.edu

Principal Investigator: Karen L Herbst, MD, PhD

Sub-Investigator: Sara Al-Ghadban, PhD

Sponsors and Collaborators

University of Arizona

Lipedema Foundation

Investigators

• Principal Investigator: Karen L Herbst, PhD, MD; University of Arizona

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Allen M, Schwartz M, Herbst KL. Interstitial Fluid in Lipedema and Control Skin. Womens Health Rep (New Rochelle). 2020 Oct 14;1(1):480-487. doi: 10.1089/whr.2020.0086. eCollection 2020.

• Responsible Party: KHerbst, Associate Professor, University of Arizona
• ClinicalTrials.gov Identifier: NCT02838277
• Other Study ID Numbers: 1602399502A001
• First Posted: July 20, 2016
• Last Update Posted: September 15, 2017
• Last Verified: September 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The data will be shared with investigators who submit a request.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by KHerbst, University of Arizona:

lymphatic vessels; leaky vessels; hypertrophic adipocyte

Additional relevant MeSH terms:

Lipedema; Lipoma; Familial Multiple Lipomatosis; Lipomatosis; Lipomatosis, Multiple Symmetrical; Adiposis Dolorosa; Connective Tissue Diseases; Skin Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Genetic Diseases, Inborn; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms