Copper Impact on Venous Insufficiency and Lipodermatosclerosis

Study Overview
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Brief Summary
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Venous disease has an adverse impact on the quality of life of patients and the NHS spends considerable resources on this chronic condition. Copper has been shown to promote new blood vessel formation and therefore improve blood supply to the affected area and possibly skin conditions. Copper has also been shown to have strong antimicrobial properties. We plan to perform a study whereby patients who would normally be given leg stockings will be asked to wear similar stockings except that one of the stockings will contain copper fibers. Neither the patient nor the clinician will know which is which. Photographs of the leg conditions will be taken at baseline, 2, 4 and 8 weeks to evaluate healing. Benefit will be evaluated by a symptom questionnaire, severity scoring tools and healing scores taken from the serial photographs.

Detailed Description
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This is a randomised controlled pilot study to assess the feasibility of copper impregnated stockings. All patients with CEAP classification 4 in both legs and venous disease identified by venous duplex will be recruited from the vascular clinics within Croydon Health Services over a period of three months. All patients will be given a patient information sheet describing the study prior to consent. Patients will be giving adequate time to read the information. Informed consent and the agreement for photography of their legs will be obtained. Patients will be assessed at baseline and at 2, 4 and 8 weeks follow-up. Copper impregnated stockings: All patients will be asked to wear compression stockings (14-18mmHg). These closed-toe and below-the-knee stockings are made of 88% nylon, 5% elastin, and 7% spandex and come in various sizes. One of the pair will have copper oxide ions permanently attached to the nylon fibres and these stockings will contain 2-3% copper ions. The patients will wear a copper stocking on one leg (study leg) and a non-copper stocking on the other (control leg). Both the patients and the clinicians will be blinded to the copper impregnated stocking. Randomisation: All stockings are marked with an 'L' for the left or 'R' for the right foot. The manufacturer has randomly marked the copper stockings with an 'L' or 'R' and paired these with a non-copper stocking. A closed envelope will contain the unique numbers of all the pairs of stockings and the information on which sock contains the copper. This envelope will remain closed for the whole recruitment period. Patient data, history and physical examination: Demographic data such as age, ethnicity, height and weight will be collected. Past medical history such as concomitant (chronic) diseases and the use of medications will be obtained. At each visit, subjective symptoms will be obtained using the Aberdeen Varicose Veins Questionnaire (AVVQ). For obtaining objective signs, the CEAP classification and the Venous Clinical Severity Scoring (VCSS) will be performed for grading the severity of the venous insufficiency per leg individually, and photographs with the Eykona® 3D camera will be taken. All data sets will be coded and anonymised. The data will be stored in a secure room within the Trust. All electronic data will be stored within password protected IT system within the Trust, which is only accessible by the clinical and research team. Eykona® Wound Measurement System: Skin changes associated with lipodermatosclerosis such as erythema, induration, hyperpigmentation and white atrophy, will be measured using the Eykona® Wound Measuring System (Type EYK10001). This system contains a 3D portable camera with software that enables precise measurements of wound size and tissue condition. Photographs will be taken at each visit. The surface area of the skin changes will be calculated. Statistical analysis: Statistical analysis will be performed using SPSS version 20.0 or higher. The CEAP classification, the Venous Clinical Severity Score and the AVVQ score at the 2, 4, and 8 weeks assessment will be compared with the baseline scores. The length, width and surface area of the skin condition from the leg with the copper will be compared with the control leg and the measurements at the 2, 4, and 8 weeks assessment will be compared with the baseline measurements. Paired t-test will be used for continuous data at baseline and a multilevel (mixed) regression model will be used to analyse the change over time. Sample size calculation: The sample size for this study will be 15. This number is based on the prevalence of the disease in this hospital over three months' time. There is no existing data available to allow a sample size calculation. The data collection of this pilot study will enable power calculation for a larger multicentre study.

Official Title
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Impact of Copper Compression Stockings on Venous Insufficiency and Lipodermatosclerosis: a Randomised Controlled Trial

Conditions
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Lipodermatosclerosis, Chronic Venous Insufficiency, Venous Insufficiency, Varicose Veins

Intervention / Treatment
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* Other: Copper impregnated compression stocking
* Other: Normal compression stocking


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients CEAP classification 4 in both legs Venous disease confirmed by venous duplex Ability to understand and read the patient information sheet (in English) Ability to give informed consent Exclusion Criteria: Inability to give consent Pregnancy Current ulceration Wilson's disease Allergy to copper Arterial insufficiency of the lower extremities
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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All participants will be asked to wear compression stockings. One of the pair will have copper oxide ions permanently attached to the nylon fibres and these stockings will contain 2-3% copper ions. The participants will wear a copper stocking on one leg (study leg) and a non-copper stocking on the other (control leg).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Copper impregnated compression stocking<br>Copper compression stocking containing 2-3% copper ions to be worn on one leg, daily for 8 weeks. | Other: Copper impregnated compression stocking<br>* Copper impregnated compression stocking<br>|
| Placebo Comparator: Normal compression stocking<br>Similar compression stocking without copper to be worn on the other leg, daily for 8 weeks | Other: Normal compression stocking<br>* Normal compression stocking without copper<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aberdeen Varicose Vein Questionnaire (AVVQ) | Validated questionnaire consisting of 13 questions on signs and symptoms of chronic venous insufficiency for each leg seperately and questions on compression stocking usage and quality of life. The scoring of the questionnaire is from 0, which indicates no effect on the patient, to 100, which indicates a severe effect. | 2 weeks | 
| Venous Clinical Severity Scoring (VCSS) | Assessment tool consisting of 10 items: pain, varicose veins, oedema, skin pigmentation, inflammation, induration, ulceration (number, size and duration) and use of compression therapy, which are scored on a severity scale from 0 to 3. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipodermatosclerosis surface area | Surface area of the affected skin measured using 3D photographs with the Eykona® Wound Measuring System (Type EYK10001). | 2, 4 and 8 weeks after wearing compression stockings | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Copper Oxide, Compression Therapy, Chronic Venous Disease, Randomised Controlled Trial, Lipodermatosclerosis