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

Copper Impact on Venous Insufficiency and Lipodermatosclerosis



Sponsors


Source

Croydon Health Services NHS Trust

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


Brief Summary

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

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 (Appendix 1 Patient Information Sheet). Patients will
be giving adequate time to read the information. Informed consent and the agreement for
photography of their legs will be obtained (Appendix 2 Informed Consent). 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 (Appendix 3
Datasheet). 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 (Appendix 4 Datasheet) 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.

Overall Status

Completed

Start Date

2015-09-23

Completion Date

2017-01-09

Primary Completion Date

2017-01-09

Phase

N/A

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Aberdeen Varicose Vein Questionnaire (AVVQ)
2 weeks
Venous Clinical Severity Scoring (VCSS)
24 hours

Secondary Outcome

Measure

Time Frame

Lipodermatosclerosis surface area
2, 4 and 8 weeks after wearing compression stockings

Enrollment

16

Conditions


Intervention

Intervention Type

Other

Intervention Name


Description

Copper impregnated compression stocking

Arm Group Label

Copper impregnated compression stocking


Intervention Type

Other

Intervention Name


Description

Normal compression stocking without copper

Arm Group Label

Normal compression stocking



Eligibility

Criteria

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

Gender

All

Minimum Age

N/A

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Abdul H Sultan
Principal Investigator
Croydon Health Services NHS Trust

Verification Date

2017-09-01

Lastchanged Date

2017-09-13

Firstreceived Date

2017-09-13

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

Croydon Health Services NHS Trust

Investigator Full Name

Mr Abdul H Sultan

Investigator Title

Consultant Obstetrician and Gynaecologist


Keywords


Has Expanded Access

No

Condition Browse


Number Of Arms

2

Intervention Browse

Mesh Term

Copper


Arm Group

Arm Group Label

Copper impregnated compression stocking

Arm Group Type

Experimental

Description

Copper compression stocking containing 2-3% copper ions to be worn on one leg, daily for 8 weeks.


Arm Group Label

Normal compression stocking

Arm Group Type

Placebo Comparator

Description

Similar compression stocking without copper to be worn on the other leg, daily for 8 weeks



Firstreceived Results Date

N/A

Reference

Citation

Rabe E, Guex JJ, Puskas A, Scuderi A, Fernandez Quesada F; VCP Coordinators. Epidemiology of chronic venous disorders in geographically diverse populations: results from the Vein Consult Program. Int Angiol. 2012 Apr;31(2):105-15.

PMID

22466974


Citation

Van den Oever R, Hepp B, Debbaut B, Simon I. Socio-economic impact of chronic venous insufficiency. An underestimated public health problem. Int Angiol. 1998 Sep;17(3):161-7.

PMID

9821029


Citation

Motykie GD, Caprini JA, Arcelus JI, Reyna JJ, Overom E, Mokhtee D. Evaluation of therapeutic compression stockings in the treatment of chronic venous insufficiency. Dermatol Surg. 1999 Feb;25(2):116-20.

PMID

10037516


Citation

Eklof B, Perrin M, Delis KT, Rutherford RB, Gloviczki P; American Venous Forum; European Venous Forum; International Union of Phlebology; American College of Phlebology; International Union of Angiology. Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document. J Vasc Surg. 2009 Feb;49(2):498-501. doi: 10.1016/j.jvs.2008.09.014.

PMID

19216970


Citation

Raju S, Hollis K, Neglen P. Use of compression stockings in chronic venous disease: patient compliance and efficacy. Ann Vasc Surg. 2007 Nov;21(6):790-5.

PMID

17980798


Citation

Borkow G, Gabbay J. Copper as a biocidal tool. Curr Med Chem. 2005;12(18):2163-75. Review.

PMID

16101497


Citation

O'Gorman J, Humphreys H. Application of copper to prevent and control infection. Where are we now? J Hosp Infect. 2012 Aug;81(4):217-23. doi: 10.1016/j.jhin.2012.05.009. Epub 2012 Jun 26. Review.

PMID

22738611


Citation

Borkow G, Gabbay J, Zatcoff RC. Could chronic wounds not heal due to too low local copper levels? Med Hypotheses. 2008;70(3):610-3. Epub 2007 Aug 6.

PMID

17689198


Citation

Sen CK, Khanna S, Venojarvi M, Trikha P, Ellison EC, Hunt TK, Roy S. Copper-induced vascular endothelial growth factor expression and wound healing. Am J Physiol Heart Circ Physiol. 2002 May;282(5):H1821-7.

PMID

11959648


Citation

Tenaud I, Sainte-Marie I, Jumbou O, Litoux P, Dréno B. In vitro modulation of keratinocyte wound healing integrins by zinc, copper and manganese. Br J Dermatol. 1999 Jan;140(1):26-34.

PMID

10215764


Citation

Ahmed Z, Briden A, Hall S, Brown RA. Stabilisation of cables of fibronectin with micromolar concentrations of copper: in vitro cell substrate properties. Biomaterials. 2004 Feb;25(5):803-12.

PMID

14609669


Citation

Uauy R, Olivares M, Gonzalez M. Essentiality of copper in humans. Am J Clin Nutr. 1998 May;67(5 Suppl):952S-959S. Review.

PMID

9587135


Citation

Hostynek JJ, Dreher F, Maibach HI. Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Inflamm Res. 2011 Jan;60(1):79-86. doi: 10.1007/s00011-010-0238-9. Epub 2010 Aug 20. Erratum in: Inflamm Res. 2011 Jun;60(6):611.

PMID

20721598


Citation

Weinberg, I., Lazary, A., Jefidoff, A., Vatine, J.J., Borkow, G., Ohana, N. Safety of using diapers containing copper oxide in chronic care elderly patients. Open Biol J. 2013;6:54-59.


Citation

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PMID

25901580



Acronym

CIVIL

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Intervention 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).

Primary Purpose

Supportive Care

Masking

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description

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 stocking contains the copper. This envelope will remain closed for the whole recruitment period and throughout analysis of the results.



ClinicalTrials.gov processed this data on September 14, 2017

Conditions

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Interventions

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Study Phase

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In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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