Clinical Research Directory

Multimodal Ultrasound for Differentiating Lymphedema and Lipedema

The aim of this observational study is to evaluate the diagnostic value of multimodal ultrasonography in differentiating between lymphedema and lipedema. Differentiating these two chronic conditions based solely on clinical examination can be challenging due to overlapping symptoms. This study will utilize various non-invasive ultrasound techniques-including B-mode ultrasound, strain elastography, power Doppler, and quantitative ImageJ analysis-to compare tissue characteristics among patients with lymphedema, patients with lipedema, and healthy controls. The goal is to identify reliable, non-invasive imaging biomarkers that can facilitate early and accurate diagnosis, thereby optimizing patient management.

The Impact of Metabolic Status on Pain and Central Sensitization in Women With Lipedema: A Cross-Sectional Observational Study

The aim of this study is to evaluate the effect of metabolic markers (HOMA-IR, triglyceride/HDL ratio, HbA1c, waist and hip circumference measurements, BMI, etc.) on pain and central sensitization in patients diagnosed with lipedema. The primary objective is to investigate the association between metabolic markers and central sensitization. The secondary objective is to assess the relationship between metabolic markers and pain intensity, pain phenotype, and functional status.

Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders

The purpose of this study is to demonstrate the feasibility of near-infrared fluorescence imaging in subjects with acquired or hereditary lymphedema, in subjects with lipidema and other lymphovascular disorders and in normal health subjects; in order to attempt to correlate imaging phenotype(s) with genotype(s).

Evaluation of Physical Activity in Women With Lipedema

This study will be conducted with women diagnosed with lipedema who were referred to the Lymphedema Rehabilitation Unit of the Physiotherapy and Rehabilitation Department at Gazi University Faculty of Health Sciences for physiotherapy recommendations, and with healthy controls with similar characteristics. Demographic and clinical characteristics of individuals meeting the inclusion criteria and voluntarily agreeing to participate in the study will be recorded. Based on patient statements, factors limiting physical activity due to lipedema, and experiences during and after exercise will be recorded. Additionally, individuals' exercise behavior will be assessed using the Stages of Exercise Behavior Change Questionnaire, their physical activity level using the International Physical Activity Questionnaire-Short Form, and their physical activity barriers using the Self-Perceived Barriers for Physical Activity Questionnaire Data obtained from patient statements, scales, and questionnaires will be compared.

Investigation of the Effects of High-Intensity Interval Exercise and Moderate-Intensity Continuous Exercise on Limb Volume, Functional Capacity, and Quality of Life in Patients With Lipedema

This randomized controlled clinical study aims to investigate and compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), when combined with intermittent pneumatic compression (IPC) therapy, on limb volume, functional capacity, pain, fatigue, anxiety, depression, sleep quality, and quality of life in women with lipedema. Lipedema is a chronic, progressive adipose tissue disorder primarily affecting women, characterized by abnormal and symmetrical fat accumulation in the lower extremities that does not improve with weight loss or limb elevation. It is often misdiagnosed as obesity or lymphedema, leading to delayed treatment. Lipedema causes pain, swelling, bruising, mobility limitation, and reduced quality of life. Conservative treatment options include compression therapy, manual lymphatic drainage, and exercise. IPC is a non-invasive treatment used to reduce limb volume and pain while improving function and quality of life. Exercise is also a cornerstone of conservative management, but the optimal exercise intensity for lipedema remains unclear. In this study, 69 female patients aged 18-65 years diagnosed with lipedema according to Halk and Damstra criteria will be randomly assigned into three groups: IPC + Home-based walking program IPC + High-Intensity Interval Training (HIIT) IPC + Moderate-Intensity Continuous Training (MICT) All participants will receive 15 IPC sessions (3 times per week for 5 weeks). The exercise programs (HIIT or MICT) will continue for 10 weeks, supervised by a physiotherapist. The home-based group will be encouraged to walk ≥10,000 steps daily using a pedometer application. Primary outcome: Change in limb volume measured by circumferential measurements and the truncated cone formula. Secondary outcomes: Pain (VAS), functional capacity (6-Minute Walk Test), muscle strength (dynamometry), pressure pain threshold (algometry), physical activity (IPAQ-SF), lower extremity function (LEFS), quality of life (SF-12), sleep quality (PSQI), fatigue (FSS), and anxiety/depression (HADS). Measurements will be taken at baseline (T0), after 15 IPC sessions (T1), and after 30 total sessions or 10 weeks (T2). The investigators hypothesize that both HIIT and MICT combined with IPC will provide superior improvements in physical and psychological outcomes compared to IPC with a home-based walking program alone.

Investigation of Medial Longitudinal Arch and Foot Function in Patients With Lipedema

Lipedema is a chronic adipose tissue disorder that commonly leads to joint laxity, hypermobility, and functional limitations, yet its impact on foot morphology has not been systematically examined. This case-control study aims to investigate whether patients with lipedema exhibit a higher prevalence of generalized joint hypermobility and foot structural abnormalities-specifically pes planus-compared with age- and BMI-matched controls. Using radiographic measurements (Meary angle and calcaneal inclination angle), clinical hypermobility assessment, and validated functional scales, the study seeks to determine the relationship between lipedema, hypermobility, and foot function.

Building Lipedema Research Resources

Lipedema is a disease marked by subcutaneous adipose tissue accumulation in the lower extremities of females that is accompanied by somatic pain and edema. Importantly, lipedema is commonly misdiagnosed as obesity, although it's estimated to affect a high 11% of women. Clinical diagnosis of lipedema requires specialized training not widely available at most major medical centers, and there remains a substantial need for objective tools to distinguish lipedema from obesity. There is a critical need to define specific molecular markers of disease in circulation or at the tissue-level. The purpose of this study is to create, manage, and characterize an innovative lipedema biorepository. The goal of the biorepository will be to better understand disease mechanisms of lipedema and to define specific molecular markers of disease in circulation or at the tissue-level. The long-term purpose of our studies are to help with prevention and early management of lipedema.

Vascular Lab Resource (VLR) Biorepository

This is a study of biomarkers obtained from prospectively collected subject samples and their correlation with cardiovascular and metabolic diseases. The purpose of this initiative is to develop an enduring tool to allow for collaborative research between clinicians at Cleveland Clinic Main Campus and basic scientists at the Lerner Research Institute. This collaboration will allow resources to be available to clinical and basic researchers alike. This tool will enable research of vascular disease in the Vascular Lab and will leverage this valuable asset to the fullest extent to allow for interdepartmental collaboration.

The Effect of Systematic Endurance Training in Treatment of Women With Lipedema

Lipedema is a chronic adipose tissue disorder that primarily affects women. The etiology remains unclear and involves abnormal buildup of fat mainly in the lower limbs. It causes physical and psychological morbidity, often with significant impact of daily life. Effective treatment options are still limited, primary involving conservative measures such as compression therapy. Regular endurance training is known to have positive effects on pain management in other disorders, as well as beneficial effects on obesity management. Thus, LipidEx aims to explore the potential of high-intensity interval training (HIIT) as a novel therapeutic option for women with lipedema. We will now perform a cross-over randomized controlled trial (RCT) exploring the effects of 12 weeks of HIIT compared to a control period of usual care. Primary outcomes include changes in pain, and secondary outcomes include changes in adipose tissue mass and quality of life. Exploratory outcomes include changes in inflammatory markers, metabolites, and lipoprotein subfractions in blood and adipose tissue.

ESWT for Primary Lipedema

This randomized controlled clinical trial aims to evaluate the effectiveness of extracorporeal shockwave therapy (ESWT) when added to standard conservative treatment in women with primary lipedema. Participants will be randomly assigned to receive either standard conservative therapy alone or standard therapy combined with radial ESWT. The study will assess changes in pain intensity (VAS), limb circumference measurements, quality of life (SF-36), and patient satisfaction over an 8-week period. Evaluations will be performed at baseline, at the end of the 4-week treatment phase, and at 4-week follow-up. This trial seeks to provide evidence on whether ESWT offers additional clinical benefit in the management of primary lipedema.

The National Lipedema Study

Lipedema is a chronic condition with a symmetrical accumulation of painful fatty tissue primarily affecting the limbs, sparing hands, feet and trunk. The subcutaneous fatty tissue is disproportionately voluminous and may have a different microstructure and metabolism than the patient's regular fatty tissue. The condition affects almost exclusively women and usually debuts around puberty. Lipedema seems to have a hereditary component, may be affected by hormonal variations and worsens with obesity. Guidelines advocate conservative treatment with compression therapy, weight management, physical activity, life style changes and psychological support;and in some cases surgical treatment such as bariatric surgery and liposuction. Treatment of lipedema is indicated when the condition causes significant pain and inhibits the patient's everyday activities. Well-designed randomized controlled studies on lipedema are lacking. The Ministry of Health and Care Services in Norway has found the scientific documentation for the effects of liposuction to be insufficient and has recommended that surgical treatment of lipedema should be evaluated through a 5-year clinical trial. A national task force, consisting of representatives from all four regional health authorities in Norway has been set up. This task force has now initiated this study. A national multi-center study with homogenous treatment protocols can provide globally sought insight on lipedema and the effect of its treatment regimes, and the findings will be important to adjust future treatment strategies regarding both effect and cost/effectiveness.

Investigation of Central Sensitization and Associated Factors in Patients With Lipedema

This study aims to investigate the presence of central sensitization and its associated parameters in patients with lipedema. Lipedema is a chronic and hereditary condition that primarily affects the lower extremities in women and is often associated with hormonal changes. Symptoms such as pain, swelling, and tenderness are common in lipedema, and these symptoms may be related to central sensitization. Additionally, the ultrasonographic findings and pain sensitivity in lipedema will be compared with those of healthy individuals. This study seeks to contribute to the diagnosis and treatment process of lipedema.

Proof of Concept, Randomized, and Crossover Study, to Assess the Effectiveness of Two Types of Compression Garments in Lipedema

The goal of this prospective randomized crossover experimental study is to assess the effectiveness and tolerance of circular and flat fabric garments in stabilizing lower-limb volume in lipedema. It will assess the effectiveness of the garments and determine any differences between both types of hosiery currently used in routine clinical practice. Participants will be prescribed either circular or flat-knitted pantyhose and wear them daily for 6 months. After 6 months, they will change the type of garment.

Visualizing Vascular Mechanisms of Lipedema

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.

Evaluation Between Surgical Therapy of Lipedema Compared to Complex Physical Decongestive Therapy (CDT) Alone

The purpose of this study is to determine whether surgical treatment of lipedema (stage I, II or III) using liposuction significantly improves leg pain compared to the use of complex decongestive therapy (CDT).

Effect of Ketosis on Pain and Quality of Life in Patients With Lipedema

Lipedema is a female progressive fat disorder, characterized by a symmetrical increase in subcutaneous adipose tissue in the lower extremities with the exception of the waist. The condition is often misdiagnosed and underdiagnosed. The etiology is poorly understood. Affects about 11% of all women and may lead to pain and immobility. The pathophysiology may be related to sex hormones and inflammatory response. Lipedema fat has been reported not to respond to lifestyle changes or bariatric surgery, both in terms of weight loss and symptom reduction; including pain and quality of life. Clinical research on the effect of dietary interventions on lipedema does not exist, but a pilot study with a ketogenic diet showed a significant reduction in pain regardless of weight loss. The aim of the research project will be to investigate whether a ketogenic diet can be a treatment option for patients with lipedema. Therefore, a randomized controlled trial will be conducted to compare the effects of two diets. 1) energy-restricted ketogenic diet and 3) energy-restricted low-fat non-ketogenic diet for 8 weeks. Pain and quality of life will be mesured at start and immediately after the intervention. The hypothesis is that a ketogenic diet may reduce pain and improve quality of life.

Sarcopenia and Related Factors in Lipedema

Lipedema is a common disease of subcutaneous adipose tissue. The most common complaint of patients with swelling in the affected extremity is pain. In addition, patients with lipedema may experience conditions that can greatly affect the health and quality of life of the individual, such as loss of muscle strength and exercise capacity, and deterioration in activity levels of daily living. It is still unknown whether the decrease in muscle strength in patients with lipedema is part of this condition or whether decreased activity levels lead to decreased muscle strength. Sarcopenia is an important health problem characterized by age-related loss of muscle mass and muscle function. The relationship between muscle weakness and sarcopenia in patients with lipedema has not been investigated before. Early recognition of possible sarcopenia and functional limitations in these patients may be important to increase the ability of patients to participate in physical activity as part of their conservative management. There is no study in the literature investigating sarcopenia in patients with a diagnosis of lipedema. The aim of this study is to evaluate patients with a diagnosis of lipedema in terms of sarcopenia. In addition, the relationship between sarcopenia and age, body mass index, exercise frequency, lipedema type, and stage will be investigated in patients diagnosed with lipedema.

Effects of Exercise in Patients with Lipedema

Lipedema is a chronic progressive disease characterized by symmetrical, disproportionate swelling of subcutaneous adipose tissue, which is common in women and mostly seen in the lower extremities and to a lesser extent in the upper extremities. Healthy lifestyle approaches including exercise treatments are very important for lipedema patients in order to prevent disease progression. The aim of this study is to investigate the effects of exercise on edema, pain, exercise capacity, lower extremity muscle strength and function in lipedema patients. Sociodemographic information of the patients, body composition with Tanita InnerScan BC-601-CG device, clinical information regarding lipedema, type and stage of lipedema, inspection, palpation findings will be recorded. Local tissue water percentage will be assessed using Moisturemeter-d compact (MMDc, Delfin Technologies, Kuopio, Finland) device, circumference measurement using tape, pain intensity with Visual Analog Scale, pain threshold with Baseline brand digital algometer device. Muscle strength will be assessed using K-Force hand dynamometer. Functional exercise capacity will be assessed with the 6-minute walk test (6MWT), and lower extremity dysfunction with the lower extremity functional scale. After the assessments are made, the patients will be randomly divided into 2 groups. The patients in the study group will perform group exercises consisting of warm-up, loading and cool-down periods of 40-50 minutes, 2 days a week for 6 weeks, and strengthening exercises applied to the hip muscles and knee extensors with elastic resistance bands, which are decided according to the level of effort perceived by the patient, 3 sets of 10 repetitions, 2 days a week for 6 weeks. The same assessments will be applied to the patients again at the end of the exercise program. The control group will be re-evaluated after 6 weeks with suggestions regarding lipedema and physical activity level, and the obtained data will be compared.

Telerehabilitation Versus Supervised Pilates Training in Lipedema Women

1. Pilates Exercise: The Pilates method is a low-intensity form of movement based on body control, which works the body in a complete way, promoting physical and mental health. PET is different when compared to traditional exercises, which, in turn, tend to isolate the working muscles and have specific training approaches using repetitive motions. 2. Telerehabilitation: Telehealth is emerging as a key method for delivering essential healthcare. Primary care research suggests that telehealth is acceptable and has potential to overcome geographical barriers for individuals needing many times rehabilitation by eliminating the need for extensive and costly travel 3. Diet approach: A customized low-carbohydrate high-fat (LCHF) restricted caloric diet in women with lipedema will be used for 12 weeks. The LCHF diet may be a valuable nutritional strategy for lipedema and overweight/obese women, reducing inflammatory status with a beneficial effect on weight, glucose profile the concentration of triglycerides and HDL

Investigation of Lipedema, Lymphedema and Vascular Malformations by Multispectral Optoacoustic Tomography (MSOT)

This study aims to analyze the fatty tissue architecture of the subcutaneous tissue in patients from the plastic surgery department. Plastic surgery patients show a wide variety of subcutaneous fatty tissue structures during clinical examination. These include patients with edema of the extremities such as lipedema or lymphedema. Fatty tissue architecture plays a major role in our everyday lives, as wound healing and scar formation, for example, are influenced by the blood flow to the overlying skin. The fatty tissue architecture, especially in the subcutaneous fatty tissue, also plays a major role in our appearance. An analysis of the architecture can potentially provide information about the genesis of different skin fold formations. The aim of this study is to quantitatively describe structural differences in adipose tissue architecture. Adipose tissue architecture is still a largely unexplored area because imaging has not been possible to date. MSOT imaging is similar to conventional sonography in that a transducer is placed on the skin and energy is supplied to the tissue by pulsed laser light instead of sound. On a macroscopic level, this leads to a constant change of minimal oscillations of individual tissue components. The resulting sound waves can then be detected by the same transducer. Previous studies have shown that the quantitative determination of hemoglobin can be used to obtain information on blood circulation and inflammatory activity. In the extended spectrum, in contrast, not only hemoglobin and its oxygenation stages but also other biomarkers such as collagens and lipids can be detected. This is very useful for imaging of fat, lymphatics and normal and abnormal blood vessels in vascular malformations. This process was largely researched by the working group of Prof. Ntziachristos (Helmholtz Center Munich and Technical University of Munich) and Prof. Razansky (Eidgenösische Technische Hochschule Zurich) and is being further developed into a clinically applicable technology and sold commercially by the company iThera. As a first series of demonstrative clinical studies following rigorous technical development, MSOT will serve as a key tool for research partners in the investigation of several diseases that remain poorly-understood and have limited treatment options. These parallel studies will focus on lipedema and lymphedema as well as vascular malformations - three distinct disease groups with similarly unmet clinical needs for appropriate imaging modalities and high potential of translation to further major disease areas. By focusing on two unrelated diseases, this project will show the wide-reaching application of this innovative imaging approach. Following successful proof-of-principle validation in a clinical research environment, full exploitation and dissemination of the results will strive to deliver MSOT to the greater scientific community. The main objectives are to confirm/validate the spectral profile of fat and vasculature on MSOT in lipedema patients, to establish the spectral profile of vascular malformations based on MSOT for adults and children and to establish the spectral profile and imaging of lymphatic vessels. With a detailed analysis of the architecture, our understanding of the physiology and pathology of the skin may be enhanced.