Visualizing Vascular Mechanisms of Lipedema

Lipedema Clinical Trial

— VMP  

Official title:

Visualizing Vascular Mechanisms of Lipedema

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05464927
• Other study ID #: 210181
• Secondary ID: 1R01HL157378-01
• Status: Recruiting
• Start date: September 1, 2021
• Est. completion date: January 1, 2027

Study information

• Verified date: November 2023
• Source: Vanderbilt University Medical Center
• Contact: Study Coordinator
• Phone: 615-875-9935
• Email: salt[@]vumc.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Lipedema

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in tissue sodium content: quantification of tissue sodium content in treated limbs following the completion of therapy	Tissue sodium content (mmol/L) quantified by sodium MRI	at baseline and approximately 6 weeks later
Primary	Change in lymphedema severity: quantification of lymphatic stasis in treated limbs following the completion of therapy	Lymphatic stasis area (mm^2) quantified by MR lymphangiography	at baseline and approximately 6 weeks later
Primary	Baseline tissue sodium content: quantification of tissue sodium in affected limbs	Tissue sodium content (mmol/L) quantified by sodium MRI	At baseline
Primary	Baseline lymphedema severity: quantification of lymphatic stasis in affected limbs	Lymphatic stasis area (mm^2) quantified by MR lymphangiography	At baseline
Primary	Change in limb extracellular water: quantification of limb extracellular water in treated limbs following the completion of therapy	Limb extracellular water (Ohms) estimated by bioimpedance spectroscopy	at baseline and approximately 6 weeks later
Primary	Change in skin water: quantification of skin water in treated limbs following the completion of therapy	Skin water (percent) estimated by tissue dielectric probe	at baseline and approximately 6 weeks later
Primary	Change in skin elasticity: quantification of skin elasticity in treated limbs following the completion of therapy	Skin elasticity (Newtons) quantified by fibrometer	at baseline and approximately 6 weeks later
Primary	Baseline limb extracellular water: quantification of limb extracellular water in affected limbs	Limb extracellular water (Ohms) estimated by bioimpedance spectroscopy	At baseline
Primary	Baseline skin water: quantification of skin water in affected limbs	Skin water (percent) estimated by tissue dielectric probe	At baseline
Primary	Baseline skin elasticity: quantification of skin elasticity in affected limbs	Skin elasticity (Newtons) quantified by fibrometer	At baseline