Cooling Lower Leg Skin to Prevent Venous Leg Ulcers in Patients With Poor Vein Circulation

Study Overview
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Brief Summary
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Leg vein circulation problems can damage the skin of the lower legs, especially around the ankles, by making it discolored, hard, itchy, red, and swollen. Ulcers often develop. Inflammation is often present in the damaged skin. This study will test whether using a special low compression, cooling, boot-like gel wrap placed around the damaged skin of the lower legs will improve the skin circulation and prevent leg ulcers. The study hypothesis is: A cryotherapy, low-compression cooling gel wrap (CW) plus usual care (UC) (leg elevation, compression stockings) intervention compared to a low compression non-cryotherapy sham wrap (NW) plus UC will reduce tissue blood flow (perfusion units) and decrease the incidence of venous leg ulcers (VLUs) during the 9-month study period in individuals with Stage 4 and 5 venous insufficiency.

Detailed Description
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This new trial will assess the efficacy of this home-based cryotherapy intervention by adding sequenced tapered cooling after a 30-day intense cooling period. The goal is to reduce skin blood flow of chronically inflamed skin, decrease the incidence of venous leg ulcers and pain, and improve quality of life. A myriad of surgical, pharmacologic, and non-pharmacologic therapies such as compression bandages are often tried, many with limited success. More than 70% of patients with venous disorders such as insufficiency develop edema, skin damage, and ulcers. Ulcer prevention is warranted because of the significant socioeconomic implications in terms of lost workdays and wages, decreased productivity and increased health care costs. Clinicians focus on the multiple treatment approaches, often without consideration of how patients can contribute to their own self-care. Our 9-month intervention is based on principles of heat transfer and cryotherapy theories involving microcirculation. With input from a cryotherapy expert and participants who completed the R21 pilot, the investigators propose a sequenced intervention strategy, where cooling will be dosed daily for 30 minutes for the first month, and then decreased to twice weekly dosing in months 2-3, once weekly in months 4-6, then PRN in months 7-9. The investigators will measure blood flow, skin temperature, pain, quality of life, and the incidence of leg ulcers after months 1, 3, 6 and 9. Eligible participants will be randomized to treatment (low compression cooling wrap) or usual care (low compression non-cooling sham wrap). Participants in both groups will receive all study related materials including standardized instruction, skin thermometer, specially designed low compression wraps, leg elevator pillow, and compression stockings, and during an in-depth orientation session. The investigators hypothesize that cryotherapy will enhance the largely ineffective non-pharmacologic self-care usual care model, that is, telling patients to wear compression stockings, elevate the legs, and get more exercise. These strategies are generally inadequate in achieving sustained change. Among our research methods the investigators include rigorous process, impact and outcome monitoring. In an era of expectation for technological and pharmaceutical fixes, this self-care strategy, if efficacious, could be an economical way to decrease morbidity and pain for thousands of patients, frequently viewed as non-responsive to self care. Prevention of ulcers is also a major potential source of saved medical dollars. This trial is significant due to the burden of venous disorders, the complex physical characteristics of the population including excessive obesity and co-morbidity and the need to reach patients with a feasible, motivational, and supportive strategy to promote self-care. The objective is to establish a new practice standard for prevention.

Official Title
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Preventing Venous Leg Ulcers With Cryotherapy: A Randomized Clinical Trial

Conditions
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Venous Disease, Venous Vascular Diseases and Syndromes, Venous Insufficiency, Venous Ulcers

Intervention / Treatment
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* Procedure: Cryotherapy: Cooling gel wrap
* Procedure: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 21 years or older CEAP Classification: Stage C4 (skin damage) and 5 (healed VLU) - leg ulcer healed within past month with intact epithelium history of healed VLU within past 2 years ankle brachial index (ABI) 0.80 - 1.3 mmHG, absence of peripheral arterial disease intact skin sensation intact thermal sensation agreement to ear compression during waking hours phone, email or mail accessible willingness to make 5 study visits including baseline able to understand protocol by passing test after watching DVD standardized instructions for low literacy able to perform required protocol activities ability to speak English Exclusion Criteria: diagnosed arterial disease or ABI <0.80 or >1.3 mm Hg (blood flow to the skin is reduced in arterial disease and cooling could cause tissue ischemia) surgical procedures on leg in past 1 year (can affect venous circulation/cause edema) open leg/foot ulcers recent leg infection within past month (increased inflammation) impaired cognitive status (cannot perform procedures) chronic inflammatory and vascular conditions where blood flow of the skin may be impacted such as Lupus erythematosus, lymphedema, Raynaud's, rheumatoid arthritis, scleroderma, end stage renal disease, chronic obstructive pulmonary disease, chronic regional pain syndrome, multiple sclerosis, hypersensitivity to cold, or patients on chemotherapy

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cryotherapy<br>Cryotherapy is delivered via a cooling gel wrap applied to the affected lower leg using a dosing regimen, starting with daily cooling in month one to PRN in the last 3 months over the 9 month study. | Procedure: Cryotherapy: Cooling gel wrap<br>* Patients will wear compression stockings (provided), elevate legs on an elevator pillow (provided) and apply the sham cyrotherapy: cooling gel wrap during the home-based intervention<br>* Other names: Cooling cuff, cool cuff;|
| Sham Comparator: Usual care<br>The sham wrap, filled with cotton, is applied to the affected lower leg using a dosing regimen, starting with daily application in month one to PRN in the last 3 months over the 9 month study. | Procedure: Usual care<br>* Patients will wear compression stockings (provided), elevate legs on an elevator pillow (provided) and apply the sham cyrotherapy wrap (sham) during the home-based intervention<br>* Other names: Guideline guided care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin blood flow |  | Skin blood flow will be measured for change at five visits: baseline (visit 1), month 1 (visit 2), month 3 (visit 3), month 6 (visit 4) and 9 (visit 5) | 
| Incidence of venous leg ulcers that develop during the study | In the event that a venous leg ulcers develops, the volunteer will notify the study personnel within 24 hours. The volunteer will be instructed to return to the primary care/wound care provider for treatment. Study personnel will contact the volunteer each week to assess progress. If the leg ulcers heals during the time enrolled in the study, the volunteer will continue with the intervention. | Time point will be assessed at months 1, 3, 6 and 9. If an ulcer develops, participants will be followed weekly, for the duration of the ulcer treatment, up to the end of the study at 9 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life |  | During the five measurement points, baseline and then after months, 1, 3, 6, and 9 | 
| Pain |  | Measured at baseline, then after months 1, 3, 6, and 9 | 
| Skin temperature |  | Will be measured daily by the subject and then by student personnel at baseline, then after months 1, 3, 6, and 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venous disease, Venous disorders, Venous insufficiency, Venous ulcers, Cryotherapy