Feasibility Study of Cryotherapy for Chronic Venous Disorders

Chronic venous disorders (CVDs) often cause long-term disability for those who experience the
worst manifestations of CVDs: disabling pain and non-healing leg ulcers. Such disabilities
have significant socioeconomic implications in terms of lost work days and wages, decreased
productivity,and ultimately increased health care costs that deteriorate the well-being and
quality of life for those who have CVD-induced illnesses. Because no reliable preventive
mechanisms exists for CVDs, this study proposes a preventive, self-management cryotherapy
intervention that targets inflamed skin of populations with CVDs at highest risk of
developing chronic leg ulcers. The proposed cryotherapy intervention will utilize a
randomized controlled clinical trial to develop a method to reduce clinical symptoms by
improving existing therapy - it is not a treatment for CVDs itself. In the proposed pilot
feasibility study, subjects will be randomized to two groups; the cryotherapy intervention
group (n=30) who will receive a four-week, cryotherapy gel wrap applied daily to the affected
skin of the lower legs in addition to the standard of care (usual care). The control group
(n=30) will receive the usual care of compression wraps or stockings applied to the lower
legs and daily leg elevation. With this method, improvement of skin microcirculation, reduced
leg pain, and improvement in quality of life will be observed. The following aims will test
the hypothesis:

Aim 1: Evaluate the feasibility of the novel intervention including treatment fidelity,
subject training, safety, and side effects associated with equipment and recruitment efforts
and further refine the intervention protocol, including questionnaires used in our previous
studies.

Aim 2: Estimate variability of outcome measurements and effect sizes needed to calculate
sample size for a subsequent larger, adequately powered, randomized clinical trial of the
efficacy of the novel cryotherapy intervention.

Aim 3: Investigate the presence of a preliminary "signal" of clinical efficacy of the
experimental treatment by evaluating trends toward statistical significance for the
hypothesis that the experimental group will experience greater reduction in skin temperature
and blood flow, greater improvement in pain, and greater improvement in quality of life.

Inclusion Criteria:

- Aged 45 years and older

- CEAP classification: stage C4 (changes in skin and subcutaneous tissue secondary to
CVDs)4a (pigmentation or eczema) 4b (lipodermatosclerosis or atrophie blanche) C5
(healed venous ulcers)

- Ankle brachial index (ABI) 0.9 - 1.3mm Hg 0 absence of peripheral arterial disease

- Intact skin sensation measured with 10 gram monofilament

- Intact thermal sensation measured with thermal sensory tester at lower leg skin and
foot surfaces

- Agreement to wear compression garments such as wraps or stockings during waking hours

- Phone, e-mail, or mail accessible

- Working freezer

Exclusion Criteria:

- ABI < 0.8 mm Hg or > 1.3 mm Hg -presence of lower extremity arterial disease (reduces
skin temperature)

- Active systemic or localized infections such as cellulitis (raises skin temperature)

- Autoimmune disorders that reduce blood flow such as Raynaud's phenomenon

- Body temperature > 37.6 degrees C (febrile state raises skin temperature)

- CEAP classification c6: active venous ulcer (cooling ulcerated skin might impair
healing)

- Known peroneal nerve injury

- Impaired skin sensation

- Unable to detect light touch measured with a 10 gram monofilament at lower leg skin
surfaces

- Unable to detect not/cold sensation measured with thermal sensory tester at lower leg
skin surfaces

- Not wearing compression or not agreeing to wear compression wraps or stockings

- Phone, e-mail, or mail inaccessible

- No working freezer