Visualizing Vascular Mechanisms of Lipedema

NCT ID: NCT05464927

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 110 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-09-01
• Study Completion Date: 2027-01-01

Brief Summary

This work will address clinical unmet needs for patients with lipedema using advanced magnetic resonance imaging (MRI) methods, in sequence with portable clinical tools, by testing fundamental hypotheses regarding potential screening methods, lymphatic therapy, and vascular dysfunction in patients with lipedema.

Detailed Description

Lipedema is a disease marked by disproportionate subcutaneous adipose tissue (SAT) accumulation in the lower extremities that is accompanied by somatic pain and edema. Importantly, lipedema is commonly misdiagnosed as obesity and has been estimated to affect a high 11% of women. However, symptoms are refractory to diet, exercise, and other interventions for obesity leading to a mean delayed diagnosis of 22 years, high physical morbidity, and lifelong distress. Despite growing awareness of lipedema as a distinct clinical entity and a recent call to action for lipedema research, fundamental gaps persist in knowledge regarding both disease mechanisms and treatment options for this debilitating disease.

Over the past four years, multi-disciplinary study from investigators in radiology, vascular medicine, and physical therapy has demonstrated that lipedema has distinct characteristics from obesity. Using whole-body fat-and-water MRI, lipedema is characterized by a 42% higher lower-extremity SAT deposition compared to BMI-matched females without lipedema (p<0.001). Using noninvasive sodium MRI technologies, skin sodium is also elevated in patients with lipedema compared to controls (14.9±2.9 vs. 11.9±2.0 mmol/L, p=0.01) in the lower extremities, but not upper extremities. Importantly, skin sodium decreases following 6-weeks of lymphatic stimulation by complete decongestive therapy (CDT) in preliminary study of patients with lipedema. These tissue signatures are consistent with those of patients with known lymphatic insufficiencies (i.e., secondary lymphedema). Recent findings of elevated arterial perfusion and inflammatory profiles in lipedema raise significant questions about how blood and lymphatic circulation are involved in lipedema.

The critical barrier to interrogating these systems, and more broadly addressing clinical unmet needs for evidence-based therapies for patients with lipedema, is that noninvasive lymphatic imaging strategies are traditionally underdeveloped. To address this barrier, non-tracer based MR lymphangiography is capable of visualizing lymphatic dilation and stasis in unilateral lymphedema, and similar features of lymphatic insufficiency are observed in the lower extremities of patients with lipedema.

This study will apply these MRI tools together with standard clinical tools to test the following hypotheses:

Hypothesis 1A: Ultrasound can be used as an accessible alternative to MRI for measuring subcutaneous fat deposition to distinguish lipedema from obesity.

Hypothesis 1B: Ultrasound measurement of fat deposition together with bedside tools for measuring water deposition have improved ability than ultrasound alone for distinguishing lipedema from controls.

Hypothesis 2: Tissue sodium is reduced following CDT in the lower extremities, but not in the untreated upper extremities, of patients with lipedema consistent with improved patient-reported outcomes.

Hypothesis 3: Lymphatic flow velocity is reduced, while arterial blood flow is elevated, in the legs of patients with lipedema compared to controls.

Conditions

Lipedema

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Participants pre CDT

• Participants with lipedema
• Biologically Female
• Age range = 18-80 years
• BMI range = 18 to 40 kg/m2
• BMI range = 18 to 40 kg/m2

No interventions assigned to this group

Controls

• Participants without lipedema
• Biologically Female
• Age range = 18-80 years
• BMI range = 18 to 40 kg/m2

No interventions assigned to this group

Participants post CDT

• Participants with lipedema
• Biologically Female
• Age range = 18-80 years
• BMI range = 18 to 40 kg/m2
• BMI range = 18 to 40 kg/m2

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Participants with and without lipedema
• Biologically Female
• Age range = 18-80 years
• BMI range = 18 to 40 kg/m2

Exclusion Criteria

• Primary lymphedema
• Contraindication to 3T MRI
• Pregnant
• Severe claustrophobia
• Inability to provide written, informed consent
• Active infection anywhere in the body, or open wound on the lower-extremities or at locations for measurement

Also excluded are subjects incapable of giving informed written consent:

• Subjects who have an inability to communicate with the researcher for any reason
• Subjects who are non-English speaking who cannot communicate through a translator, or if a translator is not available
• Subjects who cannot adhere to the experimental protocols for any reason
• Subjects who have limited mental ability to give informed consent due to mental disability, confusion, or psychiatric disorders
• Prisoners

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Rachelle Crescenzi

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rachelle Crescenzi, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

1R01HL157378-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

210181

Identifier Type: OTHER

Identifier Source: secondary_id

302197

Identifier Type: -

Identifier Source: org_study_id