Clinical trial NCT06549738: Effects of Intermittent Pneumatic Compression Therapy on Tissue Volume, Pain, and Quality of Life in Lipedema
Official title: Effects of Intermittent Pneumatic Compression Therapy on Tissue Volume, Pain, and Quality of Life in Women Living With Lipedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lipedema
Keywords: lipedema
lipoedema
Lead sponsor: Lympha Press
Sponsor class: OTHER
Collaborators: name: Carolina Vein Center
First posted: 2024-08-12
Enrollment: 46
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, controlled study planned for 50 women with lipedema with half (25) women in the Treatment group and half (25) women in the Control group. Both legs of all enrolled women will be studied for a total of 100 legs evaluated. All participants in the Treatment group will be supplied the Lympha Press Optimal Plus IPCD and the Lympha Pants™ garment to treat the lower body including the abdomen, pelvis, and buttocks (trunk) and the lower extremities. All participants in the study (Treatment and Controls) will receive compression leggings, and will be instructed to wear them daily.
Primary purpose: TREATMENT

Brief summary: Lipedema is an inflammatory and painful disease of subcutaneous adipose tissue (SAT) in women that is associated with vein disease and lymphedema. There is controversy on whether there is edema in lipedema. This study seeks to determine: 1. Is there is edema in lipedema? 2. Can edema, lipedema subcutaneous adipose tissue (SAT), symptoms, and quality of life be improved by an advanced intermittent pneumatic compression device (IPCD)?

During the course of the study subjects will be seen three times in the clinic for assessment and measurements. All subjects will be provided a compression legging at the first clinic visit. Half of the subjects (the treatment group) will be provided and use an advanced intermittent pneumatic compression device with pants-type appliance that applies dynamic compression therapy to the abdomen, hips, buttocks, legs and feet, starting at the second visit, for 30 days at home, along with daytime use of the compression legging. The other half (the control group) will use the compression leggings only. At the third visit, final measurements will be obtained. The measurements in the study include volume measurements using tape measure and a scanner; body composition measurements (bioimpedance); ultrasound and biopsy of the skin; timed walking and gait measurements; and questionnaires about pain and quality of life. Deidentified (without names) patient medical records will be examined for information on vein disease, body mass index, weight, age, and stage of lipedema (any stage or type). After the third visit, results will be analyzed.

Detailed description: Introduction Lipedema is a disease of loose connective (adipose) tissue that has no known cause or cure. One of the main features is an increased amount of abnormal fibrotic subcutaneous adipose tissue (SAT) deposited in the legs, pelvis, abdomen and/or arms of women.

Management options for lipedema focus on improving lymphatic flow, controlling edema (swelling), reducing pain or discomfort, and deep tissue therapy to try and reduce fibrosis. Intermittent pneumatic compression devices (IPCDs) are externally applied "pumps," that reduce leg swelling and improve pain and quality of life for patients with lipedema.

No study has demonstrated an improvement in fat volume (relative to total leg volume), fascia quality, and fibrosis of the leg after the use of IPCDs.

The goal of this study is to improve our understanding of lipedema tissue and how use of the IPCD, Lympha Press® Optimal Plus with Lympha Pants™ garments, may improve tissue volume, fluid, quality, quality of life, and pain levels in women with lipedema.

This is a randomized, controlled study of 50 women with lipedema with 25 women in the Treatment group and 25 women in the Control group. Women with lipedema will be recruited from women with lipedema who have had their vein disease treated. Women in this part of the study will therefore have only lipedema without active treatable vein disease. Both legs of all enrolled women will be studied for a total of 100 legs evaluated. All participants in the Treatment group will be supplied the Lympha Press Optimal Plus IPCD and the Lympha Pants™ garment to treat the lower body including the abdomen, pelvis, and buttocks (trunk) and the lower extremities. All participants in the study (Treatment and Controls) will receive compression leggings, and will be instructed to wear them daily.

Primary Aims

After use of Lympha Press® Lympha Pants™ for 30 days, changes will be assessed in:

1. Leg and abdominal tissue volume
2. Leg and abdominal fluid volume
3. Pain level
4. Quality of life

Secondary Aim 1

After use of the Lympha Press® Lympha Pants™ for 30 consecutive days, the following changes will be assessed:

1. Tissue microvasculature
2. Mobility

Secondary Aim 2

Assess the size and/or degree of insufficiency of the greater and lesser veins of the legs of women with lipedema.

Investigational Aims

After use of the Lympha Press® Lympha Pants™ for 30 consecutive days, the following changes will be assessed:

1. Hyaluronic acid and other GAG levels in the blood
2. GAG levels in adipose tissue
3. Percentage of leaky vessels in the skin
4. Tissue fascia quality
5. Tissue fibrosis

Hypotheses

Hypotheses for Primary Aims

Use of the Lympha Press® Optimal Plus with Lympha Pants™ for 30 consecutive days will:

1. Reduce size or volume of SAT measured by:

   1. Ultrasound assessment of adipose tissue depth
   2. Circumferential measurement every 10 cm from the ankle to the upper thigh using a measuring board. This will be done at the same time each day.
   3. Natural (smallest) waist with a vertical measurement to the umbilicus, and waist and hip circumferential measurements following WHO guidelines.
   4. Volumetric measurement (LymphaTech, Georgia) using a validated three-dimensional scanner handheld device.
   5. Caliper measurements under the umbilicus, on the anterior thigh and medial thigh as previously measured in women with lipedema.
2. Reduce trunk and leg fluid volume measured by bioimpedance analyses (BIA) (SoZo, Digital Health Platform, Impedimed Company, San Diego, California).
3. Reduce pain measured by a visual analogue scale.

3. Improve quality of life measured by the following two validated questionnaires:

1. RAND (Rand Healthcare, Rand.org) 36-Item Health Survey 1.0 (SF-36)
2. Lower extremity functional scale (LEFS)

Hypotheses for Secondary Aims Secondary Aim 1

Use of the Lympha Press® Lympha Pants™ for 30 consecutive days will:

Improve micro-vessel structure measured by:

1. Biopsy of the skin: Skin biopsies have previously shown that blood vessels in the dermis are oriented in a perpendicular manner to the plane of the skin suggestive of inflammation. These vessels may revert back to their normal orientation due to reduction of inflammation, fibrosis, and GAGs in the skin.
2. Thermography: We will assess changes in tissue microvasculature after use of the Lympha Press Optimal Plus with Lympha Pants by thermography photos (FLIR) of the legs and hypothesize a decrease in the overall number of visible vessels. The room temperature must be constant for repeat measurements. Non-thermogenic (regular) photos will also be taken in case body contours need to be assessed to determine locations of brighter spots in the photos representing dilated blood vessels.
3. Mobility: Women with lipedema very often have mobility limitations. We anticipate that women who initially have limited mobility will improve after using the Lympha Press Optimal Plus for 30 days at home. Mobility will be measured by:

   1. The "Timed up and Go (TUG)" test
   2. Quantitative assessment of their walk several times across a special walking mat (GAITRite) that records and analyzes the pattern of their footsteps.

Secondary Aim 2

Vein Disease - Chart Review Study: We hypothesize that there will be enlarged veins in women with lipedema with minimal venous insufficiency based on unpublished studies and previous anecdotal clinical assessments. In addition to data collected on veins in these women, we will collect body mass index, weight, age, and stage of lipedema (any stage or type). No protected health information will be collected.

Hypotheses for Investigational Aims

The use of Lympha Press Lympha Pants after 30 consecutive days will:

1. Improve tissue fascia quality: The integrity and quality of SAT superficial and deep fascia layers will be assessed by visual analogue scale analysis of ultrasound images by three independent reviewers. Images from a previous study will be used to create a 5-point scale of fascia quality which the reviewers will use to assess fascia quality from tissue ultrasounds obtained from our study subjects.
2. Decrease tissue fibrosis: SAT fibrosis will be measured by:

   1. Echogenicity of SAT and muscle.
   2. Tissue Rigidity Assessment

Subject Use of the Lympha Press Pump at Home The subjects will use the Lympha Press pump at home at least once a day for 30 days.

Day 30 Final Visit (+/- 2 days) After 30 consecutive days of daily home use of the Lympha Press Optimal Plus with Lympha Pants, legs will be assessed.

IPCD Treatment (one hour) Lympha Press Treatment. While IPCD treatment takes place, subjects will be educated on the use of the IPCD and the protocol they will follow for the home treatment phase. During the hour-long treatment session in the clinic, the pressure will be gradually increased per subject tolerance starting at 20 mm Hg.

Measures documented from the chart study including the venous duplex ultrasound exam

1. Age
2. Height
3. Weight
4. Surgical history
5. Medical history
6. Family history
7. Allergies
8. Vein reflux: sapheno-femoral junction, proximal GSV, GSV knee, GSV distal, sapheno-popliteal junction, superficial saphenous vein (SSV) proximal
9. Vein size: sapheno-femoral junction, proximal GSV, GSV knee, GSV distal, sapheno-popliteal junction, superficial saphenous vein (SSV) proximal
10. Treatment for the GSV or SSV
11. Clinical (C), Etiological (E), Anatomical (A), and Pathophysiological (P) classification of the veins

Expected outcomes of the study

Lipedema has no known cure and few treatment options are available. IPCDs have been used to manage this disease for years and have been shown to be a promising option for treatment. We anticipate the following outcomes:

1. Publication on venous disease in women with lipedema.
2. Publication on effects of the Lympha Press Optimal Plus Pump and Lympha Pants garments on:

   1. Tissue volume
   2. Pain
   3. Quality of life
   4. Mobility
3. Publication on the effect of the Lympha Press® Optimal Plus and Lympha Pants garments on fibrosis in lipedema adipose tissue.

Data management and statistical analysis Confidentiality of all subjects will be strictly protected. Each patient will have an assigned patient ID; no names or dates of birth will be included in the database. The information that makes the patient identifiable will only be available to the researchers handling the information and this information will be destroyed after 6 years.

Statistics Overarching Data Analyses Data will be collected on an excel spreadsheet and imported into GraphPad PRISM for statistical purposes and graphing. Data will only use subject numbers. Data from each visit such as volume, BIA, SAT thickness, VAS pain scores, caliper measurements, GAITrite and TUG data will be averaged for each data point and either described in the text of the publication or compared to other data points using paired t-tests or repeated measures ANOVA. Significance will be set at α\<0.05.

RAND 36-Item Health Survey 1.0 Data from the RAND 36-Item Health Survey 1.0 will be input into an excel spreadsheet. The RAND 36-Item Health Survey 1.0 assesses eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health.

Eligibility criteria: Inclusion Criteria:

1. Females age 18 - 70 years.
2. Diagnosis of Stage 2-3 Type II-III lipedema
3. Patients with an IPCD must agree to wash off the pump over 30 days prior to the study starting.
4. Must have pain score with or without pressure in any lipedema area of 3 or more out of 11-point Likert visual analogue scale.
5. Able to maintain their current diet and exercise regimen for the 60-day study.
6. Must be ambulatory.
7. Must be willing to wear compression during the study. Compression is provided at no cost as part of the study.
8. Consistent eating plan with weight stability (within 10 lbs or usual weight fluctuation per the patient) over three months.
9. Must agree to not change their diet and exercise during the study.

Exclusion Criteria:

1. Inability to understand the purpose of the study and complete consent.
2. Bed bound, preventing assessment of activities of daily living like the rest of the population we are studying.
3. Contraindications to IPCD use:

   1. serious arterial insufficiency measured as a monophasic pulse wave by Doppler
   2. edema due to decompensated congestive heart failure by history - all patients with a diagnosis of CHF will be excluded for purpose of the study
   3. active phlebitis by physical exam
   4. active deep vein thrombosis by history
   5. localized wound infection by physical exam
   6. cellulitis by physical exam
4. Lymphedema with minimal to no lipedema.
5. Positive Stemmer sign on the feet.
6. Weight \> 375 lbs. (170 kg) due to weight restriction on bioimpedance device.
7. Undergoing surgery during the time of the study.
8. Weight loss surgery within the past 18 months.
9. Use of diuretic medication.
10. Participation in another research study at the time of the study.
11. Use of immunosuppressant medications including Gleevec, diosmin, methotrexate, corticosteroids, Plaquenil or other. If they are on these medications, they must wean off for one month or not participate in this study.
12. Medical illness deemed significant by the PI.
13. Waist to hip ratio \> 0.85.
14. Undergoing manual therapy of any kind including massage, physical therapy, occupational therapy, manual lymphatic drainage therapy, instrument assisted soft tissue therapy or other deep tissue therapy. Subjects must agree to stop all manual therapy for one month prior to participation in this study.

Primary outcomes:
measure: ultrasound assessment of adipose tissue deposits
timeFrame: 30 days
measure: tissue volume assessed by tape measure
timeFrame: 30 days
measure: Volumetric measurement
timeFrame: 30 days
measure: Volumetric measurements by caliper
timeFrame: 30 days
measure: Tissue/fluid assessment by bioimpedance analysis
timeFrame: 30 days
measure: Pain measured using visual analog scale
timeFrame: 30 days
measure: Quality of life questionnaire
timeFrame: 30 days
measure: Lower extremity functional scale (LEFS)
timeFrame: 30 days
Secondary outcomes:
measure: Skin biopsy- presence of perpendicularly oriented blood vessels
timeFrame: 30 days
measure: Thermography
timeFrame: 30 days
measure: Improvement in mobility as measured by Timed Up and Go (TUG) test
timeFrame: 30 days
measure: Chart review - enlarged veins
timeFrame: 30 days
measure: Improvement in mobility as measured by the Gait-Rite device
timeFrame: 30 days
measure: Chart review for vein disease
timeFrame: 30 days
Other outcomes:
Locations:
city: Durham
country: United States
facility: Carolina Vein Center
state: North Carolina
Study officials:
affiliation: The Roxbury Institute
name: Karen L Herbst, MD, PhD
role: STUDY_CHAIR
affiliation: Carolina Vein Center
name: Lynda McHutchison
role: PRINCIPAL_INVESTIGATOR
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