Cooling Leg and Foot Ulcer Skin Post Healing to Prevent Ulcer Recurrence

Study Overview
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Brief Summary
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The goal of this study is to test MUSTCOOL, a home-based self-monitoring and self-management ulcer prevention intervention for patients with newly healed chronic venous leg and diabetic foot ulcers. Almost 90% of ulcers recur within 3 months of healing. During the six-month randomized clinic trial, skin temperature will be monitored daily, a maintenance dose of cooling gel pack or placebo will be applied three times weekly to the affected skin, and a bolus dose of cooling will be applied for 5 consecutive days if skin temperature becomes elevated. Outcomes on the incidence of leg ulcer recurrence, pain, physical activity and quality of life will be measured.

Detailed Description
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The goal of this randomized control trial is to test a patient directed self-monitoring and self-management intervention aimed at preventing the recurrence of chronic venous leg and diabetic foot ulcers using skin temperature and cryotherapy (cooling). This MUSTCOOL study is a novel ulcer prevention strategy for patients at highest risk for developing chronic ulcers; those with a previous history. The aims are to compare a cooling treatment to a placebo to determine the outcomes on ulcer recurrence, pain, physical activity and quality of life. Individuals with newly healed chronic ulcers will be invited to participate in MUSTCOOL's two component intervention: self monitoring skin temperature over targeted hot spots daily with an infrared thermometer; and maintenance cooling with a cooling pack (or placebo pack) placed over the hot spot three times each week for 30 minutes. If the temperature of the hot spot becomes elevated 2°F above baseline (average of 30 days of daily temperature readings) for 2 days in a row, a bolus regimen of 5 consecutive daily, 30 minute applications of the cooling or placebo pack will be implemented. The safety and side effects will be monitored, however, there have been no reported adverse events reported in our previous cryotherapy studies. This study was designed as a chronic ulcer prevention intervention that targets the remodeling phase, the final repair process of healing after chronic ulcer closure. The skin environment is particularly vulnerable to ulcer recurrence due to a persistent aberrant inflammatory state. The previous research conducted by the study team has demonstrated that cooling this skin reduces the abnormal metabolic activity, protecting it against ulcer recurrence. Recent advancements in infrared technology allow us to take images of the affect skin to identify the area that has the highest temperature or vulnerable hot spot. These hot spots will be self monitored by patients with newly healed ulcers in the home with an infrared thermometer that date and time stamps each reading. The study's outcomes on physical activity will be evaluated with an accelerometer. It is hypothesized that by improving the skin environment and reducing pain, patients will more likely be physically active and have better quality of life, all measurable goals for this study. This prevention strategy will be evaluated over six months in 180 patients, 90 of whom will be randomized to receive the cooling pack and 90 the placebo. The goal is to test this non-pharmacological, non-invasive clinical intervention as a tailored self-management strategy to prevent chronic ulcer recurrence. It will also determine alleviation of symptoms such as pain, and the debilitating effects on physical activity and quality of life.

Official Title
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Monitoring and Managing Newly Healed Chronic Leg and Foot Ulcer Skin Temperature: A Cooling Intervention (MUSTCOOL) to Prevent Ulcer Recurrence

Conditions
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Venous Ulcer, Venous Hypertension Ulcers, Venous Stasis Ulcer, Venous Insufficiency, Leg Ulcer, Foot Ulcer, Varicose Ulcer, Diabetic Foot

Intervention / Treatment
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* Device: Cooling gel pack
* Device: Cooling cotton pack


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly healed leg or diabetic foot ulcer within past 7 - 14 days Ankle brachial index 0.8- 1.3mmHg (rule out absence of arterial disease) Willing to wear compression stockings and appropriate footwear Working freezer Exclusion Criteria: Open leg or foot ulcers Cognitive impairment: unable to recall 2 or more words or draw clock Mini-Cog™ for cognitive impairment Chronic inflammatory or vascular conditions where blood flow of skin may be impaired such as Lupus erythematosus, Raynaud's, scleroderma, end stage renal disease, chronic regional pain syndrome, multiple sclerosis, hypersensitivity to cold, on chemotherapy Unable to preform required protocol activities without assistance (return demonstration to study staff)

Ages Eligible for Study
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Minimum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cooling gel pack<br>A cooling pack will be applied to affected leg or foot skin where an ulcer has recently healed for 30 minutes three times a week (preventive maintenance). Patients will self monitor skin temperature of affected skin daily to detect elevation and will cool the affected skin daily for 5 consecutive days (bolus) if the skin temperature becomes elevated 2°F above the baseline. | Device: Cooling gel pack<br>* Individuals will self monitor skin temperature of skin over a recently health venous leg or diabetic foot ulcer with a dermal thermometer. A cooling gel pack will be applied to skin of recently healed venous leg or diabetic foot ulcers for 30 minutes 3 times a week for six months. If the temperature of this skin site increases and stays elevated 2°F above the usual temperature of that site, the individual will cool the skin 5 consecutive days and will continue to monitor skin temperature.<br>|
| Active Comparator: Cooling cotton pack<br>A cooling cotton pack will be applied to affected leg or foot skin where an ulcer has recently healed for 30 minutes three times a week (preventive maintenance). Patients will self monitor skin temperature of affected skin daily to detect elevation and will cool the affected skin daily for 5 consecutive days (bolus) if the skin temperature becomes elevated 2°F above the baseline. | Device: Cooling cotton pack<br>* Individuals will self monitor skin temperature of skin over a recently health venous leg or diabetic foot ulcer with a dermal thermometer. A cotton filled pack will be applied to skin of recently healed venous leg or diabetic foot ulcers for 30 minutes 3 times a week for six months. If the temperature of this skin site increases and stays elevated 2°F above the usual temperature of that site, the individual will cool the skin 5 consecutive days and will continue to monitor skin temperature.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Ulcer Recurrence | Number of recurrent ulcers that develop during the 6 month study period for in participants for 4 groups of patients with previously healed venous leg ulcers receiving the cooling gel pack and cooling cotton pack and those with previously healed diabetic foot ulcers receiving the cooling gel pack or cooling cotton pack. | Through study completion at 6 months from baseline | 
| Change in Pain (Worst Pain, Least Pain, Pain Now) | Pain was measured with a visual analog scale and reported numerically (0 to 10 with 10 being the most severe pain) at baseline and at 6 months end of study | Through study completion at 6 months from baseline | 
| Differences in Step Counts | Differences in step counts reported via accelerometer data, from baseline to post treatment at 6 months end of intervention for the 4 groups. | Through study completion at 6 months from baseline | 
| Change in Mean Scores on Quality of Life Measured With the VEINES QOL/Sym Questionnaire | The Venous Insufficiency Epidemiological and Economic Study-Quality of life/Symptoms (VEINES QOL/Sym) Questionnaire was used to evaluate quality of life. A sum score is provided as an overall quality of life score for both the QOL and Sym portions of the questionnaire. This instrument was used only for the VLU groups because it is a disease-specific measure. Of the 26 items in the questionnaire, 25 items are combined to create a summary score (VEINES-QOL). One item which asks about the time of day the leg problem is most intense, question 2, provides only descriptive information and is not scored. A subset (symptoms score) of ten of these items, questions 1a to 1i and 7, is used to create a symptom score (VEINES-Sym). For both the VEINES-QOL and VEINES-Sym scores, high values indicate better outcomes. VEINES-QOL scores can be compared only to other members of the same sample. Each set of VEINES-QOL scores will have a mean T-score = 50. | Through study completion at 6 months from baseline | 
| Changes in Severity and Intensity Pain Scores Measured With the Brief Pain Inventory | The Brief Pain Inventory (BPI) scale is reported as an average score. BPI rapidly assesses the severity of pain and its impact on functioning for intensity and Pain Intensity and Pain Interference. Pain Intensity is measured in four categories: worst, least, on average, and currently, while Pain Interference is measured in 7 categories: mood, work, general activity, walking, relationships, enjoyment of life, and sleep. The patient rates each of these on a scale from 0-10, 10 being excruciating pain intensity and a complete interference in their life. Subscores are determined by averaging over the 4 intensity items for the severity subscore and over the 7 interference items for the interference subscore; possible total scores range from 0 to 10. Higher scores indicate worse intensity and severity. | Through study completion at 6 months from baseline | 
| Change in METS Minutes Engaging in Physical Activity Measured With The International Physical Activity Questionnaire | Change in metabolic equivalent of task (METS) min per week for physical activity per The International Physical Activity Questionnaire reported for 4 groups from baseline to 6 months end of study. Scoring HIGH indicate physical activity levels equate to  1hour of activity per day or more at least moderate intensity level or engage in vigorous intensity activity on at least 3 days achieving a minimum total physical activity of at least 1500 MET min a week or 7 or more days of any combination of walking, moderate intensity or vigorous intensity activities achieving a minimum total physical activity of at least 3000 MET min a week. MODERATE suggests engagement equivalent to 30 min of at least moderate intensity activity on most days; engage in 3 or more days of vigorous intensity activity and/or walking of at least 30 min per day or 5 or more days of moderate intensity activity and/or walking of at least 30 minutes per day. LOW level means that neither MODERATE or HIGH levels are met. | Through study completion at 6 months from baseline | 
| Time Spent in Minutes Engaging in Physical Activities | Mean time spent in minutes engaging in physical activities, reported via accelerometer data, from baseline to post treatment at 6 months end of intervention for the 4 groups. | Through study completion at 6 months from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Adherence to the Study Protocol | Using study data logs, appropriate use of the thermometer and cooling pack was measured by the number of participants who adhered to the protocol for taking the temperature of the skin over the healed venous leg or diabetic foot ulcer. Adherence was defined as: the number of participants who were at least 80% adherent to taking their temperatures with the infrared thermometer each morning and the number of participants who were at least 80% adherent to performing the intervention every other day = 3 times times per week during the 6-month study period. | Daily measures starting at baseline for temperature and every other day cooling application during the 6-month study period. | 
| Number of Participants Indicating 'Yes' or 'Easy' on Study Instructions, Thermometer Use, Completing Logs, Performing Treatment, Helpfulness | Patients satisfaction was measured by study personnel a during end of study phone survey with the following questions asked as follows (Yes/No): Were study instructions adequate, was thermometer easy to use, found cooling helpful, would cool skin area if it was proven that cooling prevented reulceration; (Easy/Not Easy): completing logs, performing the cooling treatment. Data are for (Yes/No) as number of participants who reported yes or if (Easy/Not Easy) the number of participants who reported easy. | Survey conducted at end of the 6-month study period. | 
| Knowledge Questionnaire of Study Instructions | Participants were administered a 12-item (yes/no) questionnaire (test) during instruction at the start of the study, provided by the research personnel to determine comprehension of the protocol and to reinforce study procedures. Score of 12 or 100% was given for all items scoring correctly (1 point per item). Any items for which no was answered, remediation was conducted by study personnel at the time the questionnaire was conducted. Means scores are reported per VLU and DFU cooling pack intervention and VLU and DFU cotton cooling pack control. | Baseline after participant enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post healed venous leg ulcer, posted healed diabetic foot ulcer